Jeff Craven

ATLANTA – Patients with rheumatoid arthritis were more at risk of postoperative infection because of a high Charlson Comorbidity Index or longer surgery time than because of perioperative use of antirheumatic medications, according to a presentation at the annual meeting of the American College of Rheumatology.

Jeff Craven/MDedge News

Anna Shmagel, MD, of the University of Minnesota in Minneapolis and colleagues performed a retrospective cohort study of 154 patients with seropositive RA who were in the Fairview Health System between Jan. 2010 and Dec. 2017 and underwent either orthopedic or major organ surgery. The patients were classified based on their use of disease-modifying antirheumatic drugs (DMARDs) and biologics alone or in combination, with patients divided into “no DMARD or biologic,” “DMARD but no biologic” and “biologic with or without DMARD” groups.

The question of whether to discontinue antirheumatic medications before surgery is still controversial, with conflicting evidence across studies, Dr. Shmagel said in her presentation. A study by Giles and colleagues found 10 of 91 patients (11%) RA who underwent an orthopedic surgical procedure developed a postoperative infection, with patients receiving tumor necrosis factor (TNF) inhibitors more likely to develop an infection, compared with patients who were not receiving TNF inhibitors (Arthritis Care Res. 2006. doi: 10.1002/art.21841).

However, other studies have challenged that idea, and a 2018 study from Goodman and colleagues raised the issue of whether patients stopping biologics prior to surgery are at increased risk of flares. Of 120 RA patients in their study who underwent total hip or total knee arthroplasty, 75% of patients flared at 6 weeks after surgery. While patients who halted biologics before surgery were more likely to flare, stopping biologics did not predict flaring after surgery (J Rheumatol. 2018. doi: 10.3899/jrheum.170366).

“It’s not entirely clear whether these theories are related to what we do with antirheumatic medications, but we felt that it was pertinent to further study this question.” Dr. Shmagel said.

Dr. Shmagel and colleagues examined the 30-day infection rate of RA patients postoperatively, with 30-day readmission and 30-day mortality rates as secondary outcomes. Patient-associated factors such as age, gender, race, body mass index, smoking status, Charlson Comorbidity Index, income, and use of corticosteroids were analyzed as covariates in addition to factors involving surgery such as expected surgery time, perioperative antibiotic use, and whether the procedure was elective or emergency surgery.

A majority of the patients in the study across all groups were white women about 63 years old with a body mass index above 30 kg/m² and almost all undergoing electing surgery compared with emergency surgery. While patients in each group were similar with regard to Charlson Comorbidity Index, expected length of surgery, and percentage of patients undergoing elective surgery, patients in the biologic with or without DMARD group had a significantly lower median income level compared with those in the other two groups (P = .01).

Overall, there were 244 surgeries in 154 patients, with 117 surgeries in the group not receiving biologics or DMARDs, 95 surgeries in the group receiving DMARDs but no biologics, and 32 surgeries in the biologics with or without DMARD group. In the DMARD but no biologics group, most patients were receiving methotrexate (45%) or hydroxychloroquine (44%), while the most common biologics in the biologics with or without DMARD group were infliximab (25%), tocilizumab (19%), abatacept (16%), etanercept (13%), rituximab (9%), and tofacitinib (9%).

There was an 11% overall rate of infection, with a similar rate of infection across all groups (P = .09). While there was a higher rate of surgical site infections among patients in the biologics with or without DMARD group (9%) and a higher percentage of urinary tract infections in the no DMARD and no biologics group (4%), the results were not statistically significant. When the rate of infections was examined by type of surgery, there were no significant differences between infections from musculoskeletal surgery (P = .7) and major organ surgery (P = .8).

The overall 30-day readmission rate was 12%, but there were no statistically significant differences between groups. Although there were five deaths in the study, four deaths were in the group not receiving DMARDs or biologics, and one death was in the biologic with or without DMARD group.

Higher Charlson Comorbidity Index did predict infection risk, with an odds ratio of 1.37 per 1-point increase in the index (95% confidence interval, 1.10-1.70). Length of surgery also increased the risk of infection, with an OR of 1.16 per 15-minute increase in surgery time (95% CI, 1.09-1.23).

Dr. Shmagel noted that the retrospective nature of the study and the midwestern cohort may mean the results are not generalizable to other populations and that larger randomized trials should be considered. “Certainly, a larger study with more events would be needed,” she said.

This study was funded by the University of Minnesota. Dr. Shmagel reported no relevant conflicts of interest.

SOURCE: Kerski M et al. Arthritis Rheumatol. 2019;71 (suppl 10), Abstract 1805.

ATLANTA – Patients with rheumatoid arthritis were more at risk of postoperative infection because of a high Charlson Comorbidity Index or longer surgery time than because of perioperative use of antirheumatic medications, according to a presentation at the annual meeting of the American College of Rheumatology.

Jeff Craven/MDedge News

Anna Shmagel, MD, of the University of Minnesota in Minneapolis and colleagues performed a retrospective cohort study of 154 patients with seropositive RA who were in the Fairview Health System between Jan. 2010 and Dec. 2017 and underwent either orthopedic or major organ surgery. The patients were classified based on their use of disease-modifying antirheumatic drugs (DMARDs) and biologics alone or in combination, with patients divided into “no DMARD or biologic,” “DMARD but no biologic” and “biologic with or without DMARD” groups.

The question of whether to discontinue antirheumatic medications before surgery is still controversial, with conflicting evidence across studies, Dr. Shmagel said in her presentation. A study by Giles and colleagues found 10 of 91 patients (11%) RA who underwent an orthopedic surgical procedure developed a postoperative infection, with patients receiving tumor necrosis factor (TNF) inhibitors more likely to develop an infection, compared with patients who were not receiving TNF inhibitors (Arthritis Care Res. 2006. doi: 10.1002/art.21841).

However, other studies have challenged that idea, and a 2018 study from Goodman and colleagues raised the issue of whether patients stopping biologics prior to surgery are at increased risk of flares. Of 120 RA patients in their study who underwent total hip or total knee arthroplasty, 75% of patients flared at 6 weeks after surgery. While patients who halted biologics before surgery were more likely to flare, stopping biologics did not predict flaring after surgery (J Rheumatol. 2018. doi: 10.3899/jrheum.170366).

“It’s not entirely clear whether these theories are related to what we do with antirheumatic medications, but we felt that it was pertinent to further study this question.” Dr. Shmagel said.

Dr. Shmagel and colleagues examined the 30-day infection rate of RA patients postoperatively, with 30-day readmission and 30-day mortality rates as secondary outcomes. Patient-associated factors such as age, gender, race, body mass index, smoking status, Charlson Comorbidity Index, income, and use of corticosteroids were analyzed as covariates in addition to factors involving surgery such as expected surgery time, perioperative antibiotic use, and whether the procedure was elective or emergency surgery.

A majority of the patients in the study across all groups were white women about 63 years old with a body mass index above 30 kg/m² and almost all undergoing electing surgery compared with emergency surgery. While patients in each group were similar with regard to Charlson Comorbidity Index, expected length of surgery, and percentage of patients undergoing elective surgery, patients in the biologic with or without DMARD group had a significantly lower median income level compared with those in the other two groups (P = .01).

Overall, there were 244 surgeries in 154 patients, with 117 surgeries in the group not receiving biologics or DMARDs, 95 surgeries in the group receiving DMARDs but no biologics, and 32 surgeries in the biologics with or without DMARD group. In the DMARD but no biologics group, most patients were receiving methotrexate (45%) or hydroxychloroquine (44%), while the most common biologics in the biologics with or without DMARD group were infliximab (25%), tocilizumab (19%), abatacept (16%), etanercept (13%), rituximab (9%), and tofacitinib (9%).

There was an 11% overall rate of infection, with a similar rate of infection across all groups (P = .09). While there was a higher rate of surgical site infections among patients in the biologics with or without DMARD group (9%) and a higher percentage of urinary tract infections in the no DMARD and no biologics group (4%), the results were not statistically significant. When the rate of infections was examined by type of surgery, there were no significant differences between infections from musculoskeletal surgery (P = .7) and major organ surgery (P = .8).

The overall 30-day readmission rate was 12%, but there were no statistically significant differences between groups. Although there were five deaths in the study, four deaths were in the group not receiving DMARDs or biologics, and one death was in the biologic with or without DMARD group.

Higher Charlson Comorbidity Index did predict infection risk, with an odds ratio of 1.37 per 1-point increase in the index (95% confidence interval, 1.10-1.70). Length of surgery also increased the risk of infection, with an OR of 1.16 per 15-minute increase in surgery time (95% CI, 1.09-1.23).

Dr. Shmagel noted that the retrospective nature of the study and the midwestern cohort may mean the results are not generalizable to other populations and that larger randomized trials should be considered. “Certainly, a larger study with more events would be needed,” she said.

This study was funded by the University of Minnesota. Dr. Shmagel reported no relevant conflicts of interest.

SOURCE: Kerski M et al. Arthritis Rheumatol. 2019;71 (suppl 10), Abstract 1805.

ATLANTA – Patients with rheumatoid arthritis were more at risk of postoperative infection because of a high Charlson Comorbidity Index or longer surgery time than because of perioperative use of antirheumatic medications, according to a presentation at the annual meeting of the American College of Rheumatology.

Jeff Craven/MDedge News

Anna Shmagel, MD, of the University of Minnesota in Minneapolis and colleagues performed a retrospective cohort study of 154 patients with seropositive RA who were in the Fairview Health System between Jan. 2010 and Dec. 2017 and underwent either orthopedic or major organ surgery. The patients were classified based on their use of disease-modifying antirheumatic drugs (DMARDs) and biologics alone or in combination, with patients divided into “no DMARD or biologic,” “DMARD but no biologic” and “biologic with or without DMARD” groups.

The question of whether to discontinue antirheumatic medications before surgery is still controversial, with conflicting evidence across studies, Dr. Shmagel said in her presentation. A study by Giles and colleagues found 10 of 91 patients (11%) RA who underwent an orthopedic surgical procedure developed a postoperative infection, with patients receiving tumor necrosis factor (TNF) inhibitors more likely to develop an infection, compared with patients who were not receiving TNF inhibitors (Arthritis Care Res. 2006. doi: 10.1002/art.21841).

However, other studies have challenged that idea, and a 2018 study from Goodman and colleagues raised the issue of whether patients stopping biologics prior to surgery are at increased risk of flares. Of 120 RA patients in their study who underwent total hip or total knee arthroplasty, 75% of patients flared at 6 weeks after surgery. While patients who halted biologics before surgery were more likely to flare, stopping biologics did not predict flaring after surgery (J Rheumatol. 2018. doi: 10.3899/jrheum.170366).

“It’s not entirely clear whether these theories are related to what we do with antirheumatic medications, but we felt that it was pertinent to further study this question.” Dr. Shmagel said.

Dr. Shmagel and colleagues examined the 30-day infection rate of RA patients postoperatively, with 30-day readmission and 30-day mortality rates as secondary outcomes. Patient-associated factors such as age, gender, race, body mass index, smoking status, Charlson Comorbidity Index, income, and use of corticosteroids were analyzed as covariates in addition to factors involving surgery such as expected surgery time, perioperative antibiotic use, and whether the procedure was elective or emergency surgery.

A majority of the patients in the study across all groups were white women about 63 years old with a body mass index above 30 kg/m² and almost all undergoing electing surgery compared with emergency surgery. While patients in each group were similar with regard to Charlson Comorbidity Index, expected length of surgery, and percentage of patients undergoing elective surgery, patients in the biologic with or without DMARD group had a significantly lower median income level compared with those in the other two groups (P = .01).

Overall, there were 244 surgeries in 154 patients, with 117 surgeries in the group not receiving biologics or DMARDs, 95 surgeries in the group receiving DMARDs but no biologics, and 32 surgeries in the biologics with or without DMARD group. In the DMARD but no biologics group, most patients were receiving methotrexate (45%) or hydroxychloroquine (44%), while the most common biologics in the biologics with or without DMARD group were infliximab (25%), tocilizumab (19%), abatacept (16%), etanercept (13%), rituximab (9%), and tofacitinib (9%).

There was an 11% overall rate of infection, with a similar rate of infection across all groups (P = .09). While there was a higher rate of surgical site infections among patients in the biologics with or without DMARD group (9%) and a higher percentage of urinary tract infections in the no DMARD and no biologics group (4%), the results were not statistically significant. When the rate of infections was examined by type of surgery, there were no significant differences between infections from musculoskeletal surgery (P = .7) and major organ surgery (P = .8).

The overall 30-day readmission rate was 12%, but there were no statistically significant differences between groups. Although there were five deaths in the study, four deaths were in the group not receiving DMARDs or biologics, and one death was in the biologic with or without DMARD group.

Higher Charlson Comorbidity Index did predict infection risk, with an odds ratio of 1.37 per 1-point increase in the index (95% confidence interval, 1.10-1.70). Length of surgery also increased the risk of infection, with an OR of 1.16 per 15-minute increase in surgery time (95% CI, 1.09-1.23).

Dr. Shmagel noted that the retrospective nature of the study and the midwestern cohort may mean the results are not generalizable to other populations and that larger randomized trials should be considered. “Certainly, a larger study with more events would be needed,” she said.

This study was funded by the University of Minnesota. Dr. Shmagel reported no relevant conflicts of interest.

SOURCE: Kerski M et al. Arthritis Rheumatol. 2019;71 (suppl 10), Abstract 1805.

ATLANTA – Patients with moderate to severe osteoarthritis of the hip and knee who took the investigational anti-nerve growth factor monoclonal antibody tanezumab experienced a significantly higher rate of joint safety events than that of patients who received NSAIDs as part of a recent randomized, double-blind, active-controlled, phase 3 study.

Jeff Craven/MDedge News

Although patients who switched from NSAIDs to 5 mg subcutaneous tanezumab every 8 weeks reported significantly improved Western Ontario and McMaster Universities (WOMAC) index pain and function scores at 16 weeks, the difference was no longer statistically significant at 56 weeks; there was an increase in the number of joint safety events in both low- and high-dose tanezumab groups when compared with patients who continued on NSAIDs, Marc C. Hochberg, MD, of the University of Maryland, Baltimore, said in his presentation at the annual meeting of the American College of Rheumatology.

“Despite prior stable doses of NSAIDs, tanezumab subcutaneously administered every 8 weeks was associated with significantly more joint safety events than NSAIDs in a dose-dependent fashion,” he said.

Dr. Hochberg and colleagues conducted a phase 3 study of tanezumab in response to a Food and Drug Administration hold on the drug in 2010 in response to reports of osteonecrosis in patients taking tanezumab. “An adjudication committee was set up at that time to review all the records of individuals who participated in those studies who had been reported to have adverse joint related events, including osteonecrosis, as well as all the elected total joint replacements,” Dr. Hochberg explained. Only 4-month safety and efficacy data for tanezumab had been reported prior to these new data with at least 1 year of follow-up.

The study comprised 2,996 patients with hip or knee osteoarthritis (OA) from 446 centers in 18 countries, where patients were randomized to receive 2.5 mg of subcutaneous tanezumab (1,002 patients), tanezumab at 5 mg (998 patients) or NSAIDs (996 patients) for up to 80 weeks. Approximately two-thirds of the patients were women, and about 70% were white. About 85% of all patients had knee OA. The most common NSAIDs were celecoxib, diclofenac, and naproxen.

Less than 1% had Kellgren-Lawrence grade 0-1 at baseline, while about 30% had grade 2, 47% grade 3, and 22% grade 4. Patients had a mean 7.0 or 7.1 score on the WOMAC pain and function subscales, and a mean Patient’s Global Assessment of OA (PGA-OA) score of 7.4 or 7.5. Baseline radiographs were taken, as well as at safety follow-ups at 24 weeks, 56 weeks, and 80 weeks.

The researchers examined rapidly progressive OA (RPOA) type 1, classified as loss of 2 mm or more of joint space width within 1 year, and type 2, which was defined as abnormal bone loss or destruction, including limited or total collapse of at least one subchondral surface. Other primary joint safety endpoints examined were primary osteonecrosis, subchondral insufficiency fracture, and pathologic fracture. Each of these was reported individually in addition to the rate of total joint replacement. If an event was discovered, it was sent to an adjudication committee, Dr. Hochberg said. “You have either investigator-reported joint safety events, possible joint safety events or identified from the central raters’ assessment of imaging, or the reported total joint replacement reviewed blindly by the adjudication committee, blinded to treatment allocation, and then the adjudication results are those that are used for the analysis,” he said.

Overall, 447 patients who received tanezumab at 2.5 mg, 419 patients who received tanezumab at 5 mg, and 446 patients who continued receive NSAIDs completed treatment. There were 71 joint safety events in the tanezumab 5-mg group (7.1%) per 1,000 person-years, compared with 39 events per 1,000 person-years in the 2.5-mg group (3.9%), and 15 events per 1,000 person-years in the NSAIDs group (1.5%). The rate of joint safety events was significantly higher in both tanezumab groups, compared with the NSAIDs group (both P less than or equal to .001). Among patients with RPOA type 1, 4.9% of patients in the 5-mg group and 2.9% of patients in the 2.5-mg tanezumab group experienced joint safety events, compared with 1.1% of patients in the NSAIDs group. While RPOA type 2, primary osteonecrosis, and subchondral insufficiency fractures were uncommon in the study, Dr. Hochberg noted there was a statistically significant difference in joint safety events between the 5-mg tanezumab group and the NSAID group for patients with RPOA type 2 (1.4% vs. 0.1%; P less than or equal to .001).

The relationship between total joint replacement and tanezumab was dose-dependent: In the 5-mg group, 8.0% of patients underwent total joint replacement, while 5.3% of patients underwent total joint replacement in the 2.5-mg group, compared with 2.6% of patients in the NSAID group. “Most of the total joint replacements were due to normal progression of osteoarthritis,” Dr. Hochberg said.

When asked if he believed there is a role for tanezumab in the management of patients with OA, Dr. Hochberg said moderate to severe symptomatic hip or knee OA, including polyarticular OA, are potential areas where tanezumab and other nerve growth factor inhibitors could be beneficial.

“There is a tremendous unmet need in this population, and these are patients who have either had an inadequate response to, are intolerant of, or have contraindications to nonsteroidal anti-inflammatory drugs, have not responded well to intra-articular therapy, or have multiple joint involvement,” he said. There is also a role for tanezumab in OA patients who don’t want to take weaker opioid analgesics such as tramadol, he added.

This study was funded by Pfizer and Lilly, and the companies sponsored the summarization of the study. The authors reported various ties with these and other companies.

SOURCE: Hochberg MC et al. Arthritis Rheumatol. 2019;71(suppl 10), Abstract 1302 and Abstract 2756.

ATLANTA – Patients with moderate to severe osteoarthritis of the hip and knee who took the investigational anti-nerve growth factor monoclonal antibody tanezumab experienced a significantly higher rate of joint safety events than that of patients who received NSAIDs as part of a recent randomized, double-blind, active-controlled, phase 3 study.

Jeff Craven/MDedge News

Although patients who switched from NSAIDs to 5 mg subcutaneous tanezumab every 8 weeks reported significantly improved Western Ontario and McMaster Universities (WOMAC) index pain and function scores at 16 weeks, the difference was no longer statistically significant at 56 weeks; there was an increase in the number of joint safety events in both low- and high-dose tanezumab groups when compared with patients who continued on NSAIDs, Marc C. Hochberg, MD, of the University of Maryland, Baltimore, said in his presentation at the annual meeting of the American College of Rheumatology.

“Despite prior stable doses of NSAIDs, tanezumab subcutaneously administered every 8 weeks was associated with significantly more joint safety events than NSAIDs in a dose-dependent fashion,” he said.

Dr. Hochberg and colleagues conducted a phase 3 study of tanezumab in response to a Food and Drug Administration hold on the drug in 2010 in response to reports of osteonecrosis in patients taking tanezumab. “An adjudication committee was set up at that time to review all the records of individuals who participated in those studies who had been reported to have adverse joint related events, including osteonecrosis, as well as all the elected total joint replacements,” Dr. Hochberg explained. Only 4-month safety and efficacy data for tanezumab had been reported prior to these new data with at least 1 year of follow-up.

The study comprised 2,996 patients with hip or knee osteoarthritis (OA) from 446 centers in 18 countries, where patients were randomized to receive 2.5 mg of subcutaneous tanezumab (1,002 patients), tanezumab at 5 mg (998 patients) or NSAIDs (996 patients) for up to 80 weeks. Approximately two-thirds of the patients were women, and about 70% were white. About 85% of all patients had knee OA. The most common NSAIDs were celecoxib, diclofenac, and naproxen.

Less than 1% had Kellgren-Lawrence grade 0-1 at baseline, while about 30% had grade 2, 47% grade 3, and 22% grade 4. Patients had a mean 7.0 or 7.1 score on the WOMAC pain and function subscales, and a mean Patient’s Global Assessment of OA (PGA-OA) score of 7.4 or 7.5. Baseline radiographs were taken, as well as at safety follow-ups at 24 weeks, 56 weeks, and 80 weeks.

The researchers examined rapidly progressive OA (RPOA) type 1, classified as loss of 2 mm or more of joint space width within 1 year, and type 2, which was defined as abnormal bone loss or destruction, including limited or total collapse of at least one subchondral surface. Other primary joint safety endpoints examined were primary osteonecrosis, subchondral insufficiency fracture, and pathologic fracture. Each of these was reported individually in addition to the rate of total joint replacement. If an event was discovered, it was sent to an adjudication committee, Dr. Hochberg said. “You have either investigator-reported joint safety events, possible joint safety events or identified from the central raters’ assessment of imaging, or the reported total joint replacement reviewed blindly by the adjudication committee, blinded to treatment allocation, and then the adjudication results are those that are used for the analysis,” he said.

Overall, 447 patients who received tanezumab at 2.5 mg, 419 patients who received tanezumab at 5 mg, and 446 patients who continued receive NSAIDs completed treatment. There were 71 joint safety events in the tanezumab 5-mg group (7.1%) per 1,000 person-years, compared with 39 events per 1,000 person-years in the 2.5-mg group (3.9%), and 15 events per 1,000 person-years in the NSAIDs group (1.5%). The rate of joint safety events was significantly higher in both tanezumab groups, compared with the NSAIDs group (both P less than or equal to .001). Among patients with RPOA type 1, 4.9% of patients in the 5-mg group and 2.9% of patients in the 2.5-mg tanezumab group experienced joint safety events, compared with 1.1% of patients in the NSAIDs group. While RPOA type 2, primary osteonecrosis, and subchondral insufficiency fractures were uncommon in the study, Dr. Hochberg noted there was a statistically significant difference in joint safety events between the 5-mg tanezumab group and the NSAID group for patients with RPOA type 2 (1.4% vs. 0.1%; P less than or equal to .001).

The relationship between total joint replacement and tanezumab was dose-dependent: In the 5-mg group, 8.0% of patients underwent total joint replacement, while 5.3% of patients underwent total joint replacement in the 2.5-mg group, compared with 2.6% of patients in the NSAID group. “Most of the total joint replacements were due to normal progression of osteoarthritis,” Dr. Hochberg said.

When asked if he believed there is a role for tanezumab in the management of patients with OA, Dr. Hochberg said moderate to severe symptomatic hip or knee OA, including polyarticular OA, are potential areas where tanezumab and other nerve growth factor inhibitors could be beneficial.

“There is a tremendous unmet need in this population, and these are patients who have either had an inadequate response to, are intolerant of, or have contraindications to nonsteroidal anti-inflammatory drugs, have not responded well to intra-articular therapy, or have multiple joint involvement,” he said. There is also a role for tanezumab in OA patients who don’t want to take weaker opioid analgesics such as tramadol, he added.

This study was funded by Pfizer and Lilly, and the companies sponsored the summarization of the study. The authors reported various ties with these and other companies.

SOURCE: Hochberg MC et al. Arthritis Rheumatol. 2019;71(suppl 10), Abstract 1302 and Abstract 2756.

ATLANTA – Patients with moderate to severe osteoarthritis of the hip and knee who took the investigational anti-nerve growth factor monoclonal antibody tanezumab experienced a significantly higher rate of joint safety events than that of patients who received NSAIDs as part of a recent randomized, double-blind, active-controlled, phase 3 study.

Jeff Craven/MDedge News

Although patients who switched from NSAIDs to 5 mg subcutaneous tanezumab every 8 weeks reported significantly improved Western Ontario and McMaster Universities (WOMAC) index pain and function scores at 16 weeks, the difference was no longer statistically significant at 56 weeks; there was an increase in the number of joint safety events in both low- and high-dose tanezumab groups when compared with patients who continued on NSAIDs, Marc C. Hochberg, MD, of the University of Maryland, Baltimore, said in his presentation at the annual meeting of the American College of Rheumatology.

“Despite prior stable doses of NSAIDs, tanezumab subcutaneously administered every 8 weeks was associated with significantly more joint safety events than NSAIDs in a dose-dependent fashion,” he said.

Dr. Hochberg and colleagues conducted a phase 3 study of tanezumab in response to a Food and Drug Administration hold on the drug in 2010 in response to reports of osteonecrosis in patients taking tanezumab. “An adjudication committee was set up at that time to review all the records of individuals who participated in those studies who had been reported to have adverse joint related events, including osteonecrosis, as well as all the elected total joint replacements,” Dr. Hochberg explained. Only 4-month safety and efficacy data for tanezumab had been reported prior to these new data with at least 1 year of follow-up.

The study comprised 2,996 patients with hip or knee osteoarthritis (OA) from 446 centers in 18 countries, where patients were randomized to receive 2.5 mg of subcutaneous tanezumab (1,002 patients), tanezumab at 5 mg (998 patients) or NSAIDs (996 patients) for up to 80 weeks. Approximately two-thirds of the patients were women, and about 70% were white. About 85% of all patients had knee OA. The most common NSAIDs were celecoxib, diclofenac, and naproxen.

Less than 1% had Kellgren-Lawrence grade 0-1 at baseline, while about 30% had grade 2, 47% grade 3, and 22% grade 4. Patients had a mean 7.0 or 7.1 score on the WOMAC pain and function subscales, and a mean Patient’s Global Assessment of OA (PGA-OA) score of 7.4 or 7.5. Baseline radiographs were taken, as well as at safety follow-ups at 24 weeks, 56 weeks, and 80 weeks.

The researchers examined rapidly progressive OA (RPOA) type 1, classified as loss of 2 mm or more of joint space width within 1 year, and type 2, which was defined as abnormal bone loss or destruction, including limited or total collapse of at least one subchondral surface. Other primary joint safety endpoints examined were primary osteonecrosis, subchondral insufficiency fracture, and pathologic fracture. Each of these was reported individually in addition to the rate of total joint replacement. If an event was discovered, it was sent to an adjudication committee, Dr. Hochberg said. “You have either investigator-reported joint safety events, possible joint safety events or identified from the central raters’ assessment of imaging, or the reported total joint replacement reviewed blindly by the adjudication committee, blinded to treatment allocation, and then the adjudication results are those that are used for the analysis,” he said.

Overall, 447 patients who received tanezumab at 2.5 mg, 419 patients who received tanezumab at 5 mg, and 446 patients who continued receive NSAIDs completed treatment. There were 71 joint safety events in the tanezumab 5-mg group (7.1%) per 1,000 person-years, compared with 39 events per 1,000 person-years in the 2.5-mg group (3.9%), and 15 events per 1,000 person-years in the NSAIDs group (1.5%). The rate of joint safety events was significantly higher in both tanezumab groups, compared with the NSAIDs group (both P less than or equal to .001). Among patients with RPOA type 1, 4.9% of patients in the 5-mg group and 2.9% of patients in the 2.5-mg tanezumab group experienced joint safety events, compared with 1.1% of patients in the NSAIDs group. While RPOA type 2, primary osteonecrosis, and subchondral insufficiency fractures were uncommon in the study, Dr. Hochberg noted there was a statistically significant difference in joint safety events between the 5-mg tanezumab group and the NSAID group for patients with RPOA type 2 (1.4% vs. 0.1%; P less than or equal to .001).

The relationship between total joint replacement and tanezumab was dose-dependent: In the 5-mg group, 8.0% of patients underwent total joint replacement, while 5.3% of patients underwent total joint replacement in the 2.5-mg group, compared with 2.6% of patients in the NSAID group. “Most of the total joint replacements were due to normal progression of osteoarthritis,” Dr. Hochberg said.

When asked if he believed there is a role for tanezumab in the management of patients with OA, Dr. Hochberg said moderate to severe symptomatic hip or knee OA, including polyarticular OA, are potential areas where tanezumab and other nerve growth factor inhibitors could be beneficial.

“There is a tremendous unmet need in this population, and these are patients who have either had an inadequate response to, are intolerant of, or have contraindications to nonsteroidal anti-inflammatory drugs, have not responded well to intra-articular therapy, or have multiple joint involvement,” he said. There is also a role for tanezumab in OA patients who don’t want to take weaker opioid analgesics such as tramadol, he added.

This study was funded by Pfizer and Lilly, and the companies sponsored the summarization of the study. The authors reported various ties with these and other companies.

SOURCE: Hochberg MC et al. Arthritis Rheumatol. 2019;71(suppl 10), Abstract 1302 and Abstract 2756.

ATLANTA – New guidelines for management of osteoarthritis of the hand, knee, and hip from the American College of Rheumatology and the Arthritis Foundation lay out a wide range of treatment options without an algorithm or hierarchy, making strong recommendations for nondrug interventions and for tailoring plans to individual patient-level factors.

Jeff Craven/MDedge News

Since the ACR last released OA management guidelines in 2012, a number of recommendations have been added, changed, and removed, and the structure of the guidelines has also changed. For instance, the new OA guidelines include a broad list of management options, Sharon L. Kolasinski, MD, chair of the ACR guidelines panel and professor of clinical medicine in the division of rheumatology at the University of Pennsylvania, Philadelphia, said in a presentation at the annual meeting of the American College of Rheumatology.

“The new guideline emphasizes comprehensive management of patients with OA, rather than a stepwise algorithm in a linear manner,” she said.

There is also no hierarchy to the recommendations, apart from the strength of the recommendation. “For any individual patient, a single option may be chosen at a particular time point, perhaps with or without other options, and may be reused in the future. For a given intervention, there might be a period of time over which it’s useful, and then the option might be changed,” Dr. Kolasinski noted.

Dr. Kolasinski advised making treatment decisions based on a patient’s disease severity, whether the patient uses medical devices, and in consideration of patient risk factors. “A history of injuries, surgical history, access to care, personal beliefs and preferences should all be brought to bear on decision making for osteoarthritis management,” she said.

The guidelines also advise considering a patient’s overall well-being and factors related to a patient’s perception of pain and function, such as mood disorders, altered sleep, chronic pain, impaired coping measures, and stress level. “Comprehensive management requires a broad assessment of how pain and function are affecting the patient with OA as a whole and recognizing that multiple options are available. They might be used in combination or change over time,” Dr. Kolasinski said.

The new guidelines place a strong emphasis on educational, behavioral, psychosocial, mind-body, and physical approaches. There are strong recommendations for the use of exercise, including aerobic, strengthening, neuromuscular, and aquatic exercise. Weight loss also carries a strong recommendation for patients with hip and knee OA, with a focus on group-based exercise, education, fitness and exercise goals, and a multidisciplinary approach using self-efficacy and self-management programs. The panels made a strong recommendation for tai chi to improve hip and knee OA. There are also strong recommendations for orthoses; aids and assistive devices such as canes, first carpometacarpal (CMC) orthoses, and tibiofemoral knee braces. Other interventions, such as Kinesio tape for first CMC joint and knee OA, hand orthoses, and patellofemoral knee braces, carried a conditional recommendation. Other conditional recommendations made by the panel were for acupuncture, thermal interventions, and radiofrequency ablation for patients with knee OA. Balance training for hip and knee OA, yoga for knee OA, and cognitive-behavioral therapy all were conditionally recommended by the panel.

The panel strongly recommended against the use of transcutaneous nerve stimulation for hip and knee OA, Dr. Kolasinski noted. The panel also conditionally recommended against use of modified shoes and pulsed vibration therapy in knee OA; lateral or medial wedged insoles, massage, and manual therapy with exercise in hip or knee OA; and iontophoresis in first CMC OA.

Jeff Craven/MDedge News

Recommendations for, against pharmacologic approaches

The ACR has changed conditional recommendations for topical NSAIDs for knee and hand OA, oral NSAIDs, and intra-articular steroids for knee and hip OA into strong recommendations for the 2019 guidelines, Dr. Kolasinski said. While the 2012 guidelines conditionally recommended against topical capsaicin for knee OA, the new guidelines conditionally recommend it.

Other pharmacologic conditional recommendations included topical NSAIDs, chondroitin sulfate, and intra-articular corticosteroid injections for hand OA, acetaminophen, and duloxetine for knee OA.

With the new recommendations come changes that some rheumatologists and health care providers may find controversial. “I think that the practicing rheumatologist may be surprised that we have a recommendation against the use of hyaluronic acid in the knee as a conditional recommendation,” Dr. Kolasinski said. “The assessment of the literature at this point really reveals that there is equivalence between intra-articular hyaluronic acid injection and intra-articular saline injection, and so it was the feeling of the panel that, really, this was worth changing the recommendation from the 2012 guideline.”

The panel made strong recommendations against use of the following pharmacologic interventions:

• Bisphosphonates.
• Glucosamine sulfate.
• Combination glucosamine sulfate-chondroitin sulfate products.
• Hydroxychloroquine.
• Methotrexate.
• Intra-articular hyaluronic acid injections in hip OA.
• Chondroitin sulfate, platelet-rich plasma injections, and stem cell injections in hip and knee OA.
• Tumor necrosis factor (TNF) inhibitors.
• Interleukin-1–receptor antagonists.

Additionally, the panel made a conditional recommendation against topical capsaicin on the hand, colchicine, fish oil, vitamin D, intra-articular hyaluronic acid injections in the first CMC, and intra-articular botulinum toxin and prolotherapy in hip and knee OA.

The panel did not recommend for or against use of yoga for hip and hand OA, topical lidocaine, pregabalin, gabapentin, selective serotonin reuptake inhibitors, serotonin norepinephrine reuptake inhibitors apart from duloxetine, tricyclic antidepressants, and anti-nerve growth factor agents.

While the panel conditionally recommended against use of opioids, they made a conditional recommendation for use of tramadol opioids, and there was “a heated discussion about that distinction,” Dr. Neogi noted in a discussion session at the meeting. “There was a recent observational study that indicated that tramadol may have an increased risk of [all-cause] mortality, but there are lots of issues of confounding by indication in that study.”

The patient panel also raised strong concerns about the ACR and the Arthritis Foundation coming out against opioids for OA management in their guidelines. “They don’t want to damn opioids, but they’re also concerned about a specialty society coming out strongly against opioids in the concern that their physicians may limit their access to opioids if they’re in a situation where nothing else is helping them,” Dr. Neogi said.

Dr. Kolasinski noted the guidelines will be published online in Arthritis & Rheumatology in December, and will appear in print in February of next year.

Dr. Kolasinski reported no relevant financial disclosures. Dr. Neogi reported relationships with EMD Serono, Merck, and Pfizer.

ATLANTA – New guidelines for management of osteoarthritis of the hand, knee, and hip from the American College of Rheumatology and the Arthritis Foundation lay out a wide range of treatment options without an algorithm or hierarchy, making strong recommendations for nondrug interventions and for tailoring plans to individual patient-level factors.

Jeff Craven/MDedge News

Since the ACR last released OA management guidelines in 2012, a number of recommendations have been added, changed, and removed, and the structure of the guidelines has also changed. For instance, the new OA guidelines include a broad list of management options, Sharon L. Kolasinski, MD, chair of the ACR guidelines panel and professor of clinical medicine in the division of rheumatology at the University of Pennsylvania, Philadelphia, said in a presentation at the annual meeting of the American College of Rheumatology.

“The new guideline emphasizes comprehensive management of patients with OA, rather than a stepwise algorithm in a linear manner,” she said.

There is also no hierarchy to the recommendations, apart from the strength of the recommendation. “For any individual patient, a single option may be chosen at a particular time point, perhaps with or without other options, and may be reused in the future. For a given intervention, there might be a period of time over which it’s useful, and then the option might be changed,” Dr. Kolasinski noted.

Dr. Kolasinski advised making treatment decisions based on a patient’s disease severity, whether the patient uses medical devices, and in consideration of patient risk factors. “A history of injuries, surgical history, access to care, personal beliefs and preferences should all be brought to bear on decision making for osteoarthritis management,” she said.

The guidelines also advise considering a patient’s overall well-being and factors related to a patient’s perception of pain and function, such as mood disorders, altered sleep, chronic pain, impaired coping measures, and stress level. “Comprehensive management requires a broad assessment of how pain and function are affecting the patient with OA as a whole and recognizing that multiple options are available. They might be used in combination or change over time,” Dr. Kolasinski said.

The new guidelines place a strong emphasis on educational, behavioral, psychosocial, mind-body, and physical approaches. There are strong recommendations for the use of exercise, including aerobic, strengthening, neuromuscular, and aquatic exercise. Weight loss also carries a strong recommendation for patients with hip and knee OA, with a focus on group-based exercise, education, fitness and exercise goals, and a multidisciplinary approach using self-efficacy and self-management programs. The panels made a strong recommendation for tai chi to improve hip and knee OA. There are also strong recommendations for orthoses; aids and assistive devices such as canes, first carpometacarpal (CMC) orthoses, and tibiofemoral knee braces. Other interventions, such as Kinesio tape for first CMC joint and knee OA, hand orthoses, and patellofemoral knee braces, carried a conditional recommendation. Other conditional recommendations made by the panel were for acupuncture, thermal interventions, and radiofrequency ablation for patients with knee OA. Balance training for hip and knee OA, yoga for knee OA, and cognitive-behavioral therapy all were conditionally recommended by the panel.

The panel strongly recommended against the use of transcutaneous nerve stimulation for hip and knee OA, Dr. Kolasinski noted. The panel also conditionally recommended against use of modified shoes and pulsed vibration therapy in knee OA; lateral or medial wedged insoles, massage, and manual therapy with exercise in hip or knee OA; and iontophoresis in first CMC OA.

Jeff Craven/MDedge News

Recommendations for, against pharmacologic approaches

The ACR has changed conditional recommendations for topical NSAIDs for knee and hand OA, oral NSAIDs, and intra-articular steroids for knee and hip OA into strong recommendations for the 2019 guidelines, Dr. Kolasinski said. While the 2012 guidelines conditionally recommended against topical capsaicin for knee OA, the new guidelines conditionally recommend it.

Other pharmacologic conditional recommendations included topical NSAIDs, chondroitin sulfate, and intra-articular corticosteroid injections for hand OA, acetaminophen, and duloxetine for knee OA.

With the new recommendations come changes that some rheumatologists and health care providers may find controversial. “I think that the practicing rheumatologist may be surprised that we have a recommendation against the use of hyaluronic acid in the knee as a conditional recommendation,” Dr. Kolasinski said. “The assessment of the literature at this point really reveals that there is equivalence between intra-articular hyaluronic acid injection and intra-articular saline injection, and so it was the feeling of the panel that, really, this was worth changing the recommendation from the 2012 guideline.”

The panel made strong recommendations against use of the following pharmacologic interventions:

• Bisphosphonates.
• Glucosamine sulfate.
• Combination glucosamine sulfate-chondroitin sulfate products.
• Hydroxychloroquine.
• Methotrexate.
• Intra-articular hyaluronic acid injections in hip OA.
• Chondroitin sulfate, platelet-rich plasma injections, and stem cell injections in hip and knee OA.
• Tumor necrosis factor (TNF) inhibitors.
• Interleukin-1–receptor antagonists.

Additionally, the panel made a conditional recommendation against topical capsaicin on the hand, colchicine, fish oil, vitamin D, intra-articular hyaluronic acid injections in the first CMC, and intra-articular botulinum toxin and prolotherapy in hip and knee OA.

The panel did not recommend for or against use of yoga for hip and hand OA, topical lidocaine, pregabalin, gabapentin, selective serotonin reuptake inhibitors, serotonin norepinephrine reuptake inhibitors apart from duloxetine, tricyclic antidepressants, and anti-nerve growth factor agents.

While the panel conditionally recommended against use of opioids, they made a conditional recommendation for use of tramadol opioids, and there was “a heated discussion about that distinction,” Dr. Neogi noted in a discussion session at the meeting. “There was a recent observational study that indicated that tramadol may have an increased risk of [all-cause] mortality, but there are lots of issues of confounding by indication in that study.”

The patient panel also raised strong concerns about the ACR and the Arthritis Foundation coming out against opioids for OA management in their guidelines. “They don’t want to damn opioids, but they’re also concerned about a specialty society coming out strongly against opioids in the concern that their physicians may limit their access to opioids if they’re in a situation where nothing else is helping them,” Dr. Neogi said.

Dr. Kolasinski noted the guidelines will be published online in Arthritis & Rheumatology in December, and will appear in print in February of next year.

Dr. Kolasinski reported no relevant financial disclosures. Dr. Neogi reported relationships with EMD Serono, Merck, and Pfizer.

ATLANTA – New guidelines for management of osteoarthritis of the hand, knee, and hip from the American College of Rheumatology and the Arthritis Foundation lay out a wide range of treatment options without an algorithm or hierarchy, making strong recommendations for nondrug interventions and for tailoring plans to individual patient-level factors.

Jeff Craven/MDedge News

Since the ACR last released OA management guidelines in 2012, a number of recommendations have been added, changed, and removed, and the structure of the guidelines has also changed. For instance, the new OA guidelines include a broad list of management options, Sharon L. Kolasinski, MD, chair of the ACR guidelines panel and professor of clinical medicine in the division of rheumatology at the University of Pennsylvania, Philadelphia, said in a presentation at the annual meeting of the American College of Rheumatology.

“The new guideline emphasizes comprehensive management of patients with OA, rather than a stepwise algorithm in a linear manner,” she said.

There is also no hierarchy to the recommendations, apart from the strength of the recommendation. “For any individual patient, a single option may be chosen at a particular time point, perhaps with or without other options, and may be reused in the future. For a given intervention, there might be a period of time over which it’s useful, and then the option might be changed,” Dr. Kolasinski noted.

Dr. Kolasinski advised making treatment decisions based on a patient’s disease severity, whether the patient uses medical devices, and in consideration of patient risk factors. “A history of injuries, surgical history, access to care, personal beliefs and preferences should all be brought to bear on decision making for osteoarthritis management,” she said.

The guidelines also advise considering a patient’s overall well-being and factors related to a patient’s perception of pain and function, such as mood disorders, altered sleep, chronic pain, impaired coping measures, and stress level. “Comprehensive management requires a broad assessment of how pain and function are affecting the patient with OA as a whole and recognizing that multiple options are available. They might be used in combination or change over time,” Dr. Kolasinski said.

The new guidelines place a strong emphasis on educational, behavioral, psychosocial, mind-body, and physical approaches. There are strong recommendations for the use of exercise, including aerobic, strengthening, neuromuscular, and aquatic exercise. Weight loss also carries a strong recommendation for patients with hip and knee OA, with a focus on group-based exercise, education, fitness and exercise goals, and a multidisciplinary approach using self-efficacy and self-management programs. The panels made a strong recommendation for tai chi to improve hip and knee OA. There are also strong recommendations for orthoses; aids and assistive devices such as canes, first carpometacarpal (CMC) orthoses, and tibiofemoral knee braces. Other interventions, such as Kinesio tape for first CMC joint and knee OA, hand orthoses, and patellofemoral knee braces, carried a conditional recommendation. Other conditional recommendations made by the panel were for acupuncture, thermal interventions, and radiofrequency ablation for patients with knee OA. Balance training for hip and knee OA, yoga for knee OA, and cognitive-behavioral therapy all were conditionally recommended by the panel.

The panel strongly recommended against the use of transcutaneous nerve stimulation for hip and knee OA, Dr. Kolasinski noted. The panel also conditionally recommended against use of modified shoes and pulsed vibration therapy in knee OA; lateral or medial wedged insoles, massage, and manual therapy with exercise in hip or knee OA; and iontophoresis in first CMC OA.

Jeff Craven/MDedge News

Recommendations for, against pharmacologic approaches

The ACR has changed conditional recommendations for topical NSAIDs for knee and hand OA, oral NSAIDs, and intra-articular steroids for knee and hip OA into strong recommendations for the 2019 guidelines, Dr. Kolasinski said. While the 2012 guidelines conditionally recommended against topical capsaicin for knee OA, the new guidelines conditionally recommend it.

Other pharmacologic conditional recommendations included topical NSAIDs, chondroitin sulfate, and intra-articular corticosteroid injections for hand OA, acetaminophen, and duloxetine for knee OA.

With the new recommendations come changes that some rheumatologists and health care providers may find controversial. “I think that the practicing rheumatologist may be surprised that we have a recommendation against the use of hyaluronic acid in the knee as a conditional recommendation,” Dr. Kolasinski said. “The assessment of the literature at this point really reveals that there is equivalence between intra-articular hyaluronic acid injection and intra-articular saline injection, and so it was the feeling of the panel that, really, this was worth changing the recommendation from the 2012 guideline.”

The panel made strong recommendations against use of the following pharmacologic interventions:

• Bisphosphonates.
• Glucosamine sulfate.
• Combination glucosamine sulfate-chondroitin sulfate products.
• Hydroxychloroquine.
• Methotrexate.
• Intra-articular hyaluronic acid injections in hip OA.
• Chondroitin sulfate, platelet-rich plasma injections, and stem cell injections in hip and knee OA.
• Tumor necrosis factor (TNF) inhibitors.
• Interleukin-1–receptor antagonists.

Additionally, the panel made a conditional recommendation against topical capsaicin on the hand, colchicine, fish oil, vitamin D, intra-articular hyaluronic acid injections in the first CMC, and intra-articular botulinum toxin and prolotherapy in hip and knee OA.

The panel did not recommend for or against use of yoga for hip and hand OA, topical lidocaine, pregabalin, gabapentin, selective serotonin reuptake inhibitors, serotonin norepinephrine reuptake inhibitors apart from duloxetine, tricyclic antidepressants, and anti-nerve growth factor agents.

While the panel conditionally recommended against use of opioids, they made a conditional recommendation for use of tramadol opioids, and there was “a heated discussion about that distinction,” Dr. Neogi noted in a discussion session at the meeting. “There was a recent observational study that indicated that tramadol may have an increased risk of [all-cause] mortality, but there are lots of issues of confounding by indication in that study.”

The patient panel also raised strong concerns about the ACR and the Arthritis Foundation coming out against opioids for OA management in their guidelines. “They don’t want to damn opioids, but they’re also concerned about a specialty society coming out strongly against opioids in the concern that their physicians may limit their access to opioids if they’re in a situation where nothing else is helping them,” Dr. Neogi said.

Dr. Kolasinski noted the guidelines will be published online in Arthritis & Rheumatology in December, and will appear in print in February of next year.

Dr. Kolasinski reported no relevant financial disclosures. Dr. Neogi reported relationships with EMD Serono, Merck, and Pfizer.

PHILADELPHIA – Elagolix has emerged as an effective second-tier treatment option for patients with dysmenorrhea attributed to endometriosis, Charles E. Miller, MD, said at the annual meeting of the American Society for Reproductive Medicine.

Jeff Craven/MDedge News

Although clinicians need prior authorization and evidence of treatment failure before prescribing Elagolix, the drug is a viable option as a second-tier treatment for patients with endometriosis-associated dysmenorrhea, said Dr. Miller, director of minimally invasive gynecologic surgery at Advocate Lutheran General Hospital in Park Ridge, Ill. “We have a drug that is very effective, that has a very low adverse event profile, and is tolerated by the vast majority of our patients.”

First-line options

NSAIDs are first-line treatment for endometriosis-related dysmenorrhea, with acetaminophen used in cases where NSAIDs are contraindicated or cause side effects such as gastrointestinal issues. Hormonal contraceptives also can be used as first-line treatment, divided into estrogen/progestin and progestin-only options that can be combined. Evidence from the literature has shown oral pills decrease pain, compared with placebo, but the decrease is not dose dependent, said Dr. Miller.

“We also know that if you use it continuously or prolonged, we find that there is going to be greater success with dysmenorrhea, and that ultimately you would use a higher-dose pill because of the greater risk of breakthrough when using a lesser dose in a continuous fashion,” he said. “Obviously if you’re not having menses, you’re not going to have dysmenorrhea.”

Other estrogen/progestin hormonal contraception such as the vaginal ring or transdermal patch also have been shown to decrease dysmenorrhea from endometriosis, with one study showing a reduction from 17% to 6% in moderate to severe dysmenorrhea in patients using the vaginal ring, compared with patients receiving oral contraceptives. In a separate randomized, controlled trial, “dysmenorrhea was more common in patch users, so it doesn’t appear that the patch is quite as effective in terms of reducing dysmenorrhea,” said Dr. Miller (JAMA. 2001 May 9. doi: 10.1001/jama.285.18.2347).

Compared with combination hormone therapy, there has been less research conducted on progestin-only hormone contraceptives on reducing dysmenorrhea from endometriosis. For example, there is little evidence for depot medroxyprogesterone acetate in reducing dysmenorrhea, but rather with it causing amenorrhea; one study showed a 50% amenorrhea rate at 1 year. “The disadvantage, however, in our infertile population is ultimately getting the menses back,” said Dr. Miller.

IUDs using levonorgestrel appear comparable with gonadotropin-releasing hormone (GnRH) agonists in reducing endometriosis-related pain; in one study, most women treated with either of these had visual analogue scores of less than 3 at 6 months of treatment. Between 68% and 75% of women with dysmenorrhea who receive an implantable contraceptive device with etonogestrel report decreased pain, and one meta-analysis reported 75% of women had “complete resolution of dysmenorrhea.” Concerning progestin-only pills, they can be used for endometriosis-related dysmenorrhea, but they are “problematic in that there’s a lot of breakthrough bleeding, and often times that is associated with pain,” said Dr. Miller.

Second-tier options

Injectable GnRH agonists are effective options as second-tier treatments for endometriosis-related dysmenorrhea, but patients are at risk of developing postmenopausal symptoms such as hot flashes, insomnia, spotting, and decreased libido. “One advantage to that is, over the years and particularly something that I’ve done with my endometriosis-related dysmenorrhea, is to utilize add-back with these patients,” said Dr. Miller, who noted that patients on 2.5 mg of norethindrone acetate and 0.5 mg of ethinyl estradiol“do very well” with that combination of add-back therapy.

Elagolix is the most recent second-tier treatment option for these patients, and was studied in the Elaris EM-I and Elaris EM-II trials in a once-daily dose of 150 mg and a twice-daily dose of 200 mg. In Elaris EM-1, 76% of patients in the 200-mg elagolix group had a clinical response, compared with 46% in the 150-mg group and 20% in the placebo group (N Engl J Med. 2017 Jul 6. doi: 10.1056/NEJMoa1700089). However, patients should not be on elagolix at 200 mg for more than 6 months, while patients receiving elagolix at 150 mg can stay on the treatment for up to 2 years.

Patients taking elagolix also showed postmenopausal symptoms, with 24% in the 150-mg group and 46% in the 200-mg group experiencing hot flashes, compared with 9% of patients in the placebo group. While 6% of patients in the 150-mg group and 10% in the 200-mg group discontinued because of adverse events, 1% and 3% of patients in the 150-mg and 200-mg group discontinued because of hot flashes or night sweats, respectively. “Symptoms are well tolerated, far different than in comparison with leuprolide acetate and GnRH agonists,” said Dr. Miller.

There also is a benefit to how patients recover from bone mineral density (BMD) changes after remaining on elagolix, Dr. Miller noted. In patients who received elagolix for 12 months at doses of 150 mg and 200 mg, there was an increase in lumbar spine BMD recovered 6 months after discontinuation, with patients in the 150-mg group experiencing a recovery close to baseline BMD levels. Among patients who discontinued treatment, there also was a quick resumption in menses for both groups: 87% of patients in the 150 mg group and 88% of patients in the 200-mg group who discontinued treatment after 6 months had resumed menses by 2 months after discontinuation, while 95% of patients in the 150-mg and 91% in the 200-mg group who discontinued after 12 months resumed menses by 2 months after discontinuation.

Dr. Miller reported relationships with AbbVie, Allergan, Blue Seas Med Spa, Espiner Medical, Gynesonics, Halt Medical, Hologic, Karl Storz, Medtronic, and Richard Wolf in the form of consultancies, grants, speakers’ bureau appointments, stock options, royalties, and ownership interests.

PHILADELPHIA – Elagolix has emerged as an effective second-tier treatment option for patients with dysmenorrhea attributed to endometriosis, Charles E. Miller, MD, said at the annual meeting of the American Society for Reproductive Medicine.

Jeff Craven/MDedge News

Although clinicians need prior authorization and evidence of treatment failure before prescribing Elagolix, the drug is a viable option as a second-tier treatment for patients with endometriosis-associated dysmenorrhea, said Dr. Miller, director of minimally invasive gynecologic surgery at Advocate Lutheran General Hospital in Park Ridge, Ill. “We have a drug that is very effective, that has a very low adverse event profile, and is tolerated by the vast majority of our patients.”

First-line options

NSAIDs are first-line treatment for endometriosis-related dysmenorrhea, with acetaminophen used in cases where NSAIDs are contraindicated or cause side effects such as gastrointestinal issues. Hormonal contraceptives also can be used as first-line treatment, divided into estrogen/progestin and progestin-only options that can be combined. Evidence from the literature has shown oral pills decrease pain, compared with placebo, but the decrease is not dose dependent, said Dr. Miller.

“We also know that if you use it continuously or prolonged, we find that there is going to be greater success with dysmenorrhea, and that ultimately you would use a higher-dose pill because of the greater risk of breakthrough when using a lesser dose in a continuous fashion,” he said. “Obviously if you’re not having menses, you’re not going to have dysmenorrhea.”

Other estrogen/progestin hormonal contraception such as the vaginal ring or transdermal patch also have been shown to decrease dysmenorrhea from endometriosis, with one study showing a reduction from 17% to 6% in moderate to severe dysmenorrhea in patients using the vaginal ring, compared with patients receiving oral contraceptives. In a separate randomized, controlled trial, “dysmenorrhea was more common in patch users, so it doesn’t appear that the patch is quite as effective in terms of reducing dysmenorrhea,” said Dr. Miller (JAMA. 2001 May 9. doi: 10.1001/jama.285.18.2347).

Compared with combination hormone therapy, there has been less research conducted on progestin-only hormone contraceptives on reducing dysmenorrhea from endometriosis. For example, there is little evidence for depot medroxyprogesterone acetate in reducing dysmenorrhea, but rather with it causing amenorrhea; one study showed a 50% amenorrhea rate at 1 year. “The disadvantage, however, in our infertile population is ultimately getting the menses back,” said Dr. Miller.

IUDs using levonorgestrel appear comparable with gonadotropin-releasing hormone (GnRH) agonists in reducing endometriosis-related pain; in one study, most women treated with either of these had visual analogue scores of less than 3 at 6 months of treatment. Between 68% and 75% of women with dysmenorrhea who receive an implantable contraceptive device with etonogestrel report decreased pain, and one meta-analysis reported 75% of women had “complete resolution of dysmenorrhea.” Concerning progestin-only pills, they can be used for endometriosis-related dysmenorrhea, but they are “problematic in that there’s a lot of breakthrough bleeding, and often times that is associated with pain,” said Dr. Miller.

Second-tier options

Injectable GnRH agonists are effective options as second-tier treatments for endometriosis-related dysmenorrhea, but patients are at risk of developing postmenopausal symptoms such as hot flashes, insomnia, spotting, and decreased libido. “One advantage to that is, over the years and particularly something that I’ve done with my endometriosis-related dysmenorrhea, is to utilize add-back with these patients,” said Dr. Miller, who noted that patients on 2.5 mg of norethindrone acetate and 0.5 mg of ethinyl estradiol“do very well” with that combination of add-back therapy.

Elagolix is the most recent second-tier treatment option for these patients, and was studied in the Elaris EM-I and Elaris EM-II trials in a once-daily dose of 150 mg and a twice-daily dose of 200 mg. In Elaris EM-1, 76% of patients in the 200-mg elagolix group had a clinical response, compared with 46% in the 150-mg group and 20% in the placebo group (N Engl J Med. 2017 Jul 6. doi: 10.1056/NEJMoa1700089). However, patients should not be on elagolix at 200 mg for more than 6 months, while patients receiving elagolix at 150 mg can stay on the treatment for up to 2 years.

Patients taking elagolix also showed postmenopausal symptoms, with 24% in the 150-mg group and 46% in the 200-mg group experiencing hot flashes, compared with 9% of patients in the placebo group. While 6% of patients in the 150-mg group and 10% in the 200-mg group discontinued because of adverse events, 1% and 3% of patients in the 150-mg and 200-mg group discontinued because of hot flashes or night sweats, respectively. “Symptoms are well tolerated, far different than in comparison with leuprolide acetate and GnRH agonists,” said Dr. Miller.

There also is a benefit to how patients recover from bone mineral density (BMD) changes after remaining on elagolix, Dr. Miller noted. In patients who received elagolix for 12 months at doses of 150 mg and 200 mg, there was an increase in lumbar spine BMD recovered 6 months after discontinuation, with patients in the 150-mg group experiencing a recovery close to baseline BMD levels. Among patients who discontinued treatment, there also was a quick resumption in menses for both groups: 87% of patients in the 150 mg group and 88% of patients in the 200-mg group who discontinued treatment after 6 months had resumed menses by 2 months after discontinuation, while 95% of patients in the 150-mg and 91% in the 200-mg group who discontinued after 12 months resumed menses by 2 months after discontinuation.

Dr. Miller reported relationships with AbbVie, Allergan, Blue Seas Med Spa, Espiner Medical, Gynesonics, Halt Medical, Hologic, Karl Storz, Medtronic, and Richard Wolf in the form of consultancies, grants, speakers’ bureau appointments, stock options, royalties, and ownership interests.

PHILADELPHIA – Elagolix has emerged as an effective second-tier treatment option for patients with dysmenorrhea attributed to endometriosis, Charles E. Miller, MD, said at the annual meeting of the American Society for Reproductive Medicine.

Jeff Craven/MDedge News

Although clinicians need prior authorization and evidence of treatment failure before prescribing Elagolix, the drug is a viable option as a second-tier treatment for patients with endometriosis-associated dysmenorrhea, said Dr. Miller, director of minimally invasive gynecologic surgery at Advocate Lutheran General Hospital in Park Ridge, Ill. “We have a drug that is very effective, that has a very low adverse event profile, and is tolerated by the vast majority of our patients.”

First-line options

NSAIDs are first-line treatment for endometriosis-related dysmenorrhea, with acetaminophen used in cases where NSAIDs are contraindicated or cause side effects such as gastrointestinal issues. Hormonal contraceptives also can be used as first-line treatment, divided into estrogen/progestin and progestin-only options that can be combined. Evidence from the literature has shown oral pills decrease pain, compared with placebo, but the decrease is not dose dependent, said Dr. Miller.

“We also know that if you use it continuously or prolonged, we find that there is going to be greater success with dysmenorrhea, and that ultimately you would use a higher-dose pill because of the greater risk of breakthrough when using a lesser dose in a continuous fashion,” he said. “Obviously if you’re not having menses, you’re not going to have dysmenorrhea.”

Other estrogen/progestin hormonal contraception such as the vaginal ring or transdermal patch also have been shown to decrease dysmenorrhea from endometriosis, with one study showing a reduction from 17% to 6% in moderate to severe dysmenorrhea in patients using the vaginal ring, compared with patients receiving oral contraceptives. In a separate randomized, controlled trial, “dysmenorrhea was more common in patch users, so it doesn’t appear that the patch is quite as effective in terms of reducing dysmenorrhea,” said Dr. Miller (JAMA. 2001 May 9. doi: 10.1001/jama.285.18.2347).

Compared with combination hormone therapy, there has been less research conducted on progestin-only hormone contraceptives on reducing dysmenorrhea from endometriosis. For example, there is little evidence for depot medroxyprogesterone acetate in reducing dysmenorrhea, but rather with it causing amenorrhea; one study showed a 50% amenorrhea rate at 1 year. “The disadvantage, however, in our infertile population is ultimately getting the menses back,” said Dr. Miller.

IUDs using levonorgestrel appear comparable with gonadotropin-releasing hormone (GnRH) agonists in reducing endometriosis-related pain; in one study, most women treated with either of these had visual analogue scores of less than 3 at 6 months of treatment. Between 68% and 75% of women with dysmenorrhea who receive an implantable contraceptive device with etonogestrel report decreased pain, and one meta-analysis reported 75% of women had “complete resolution of dysmenorrhea.” Concerning progestin-only pills, they can be used for endometriosis-related dysmenorrhea, but they are “problematic in that there’s a lot of breakthrough bleeding, and often times that is associated with pain,” said Dr. Miller.

Second-tier options

Injectable GnRH agonists are effective options as second-tier treatments for endometriosis-related dysmenorrhea, but patients are at risk of developing postmenopausal symptoms such as hot flashes, insomnia, spotting, and decreased libido. “One advantage to that is, over the years and particularly something that I’ve done with my endometriosis-related dysmenorrhea, is to utilize add-back with these patients,” said Dr. Miller, who noted that patients on 2.5 mg of norethindrone acetate and 0.5 mg of ethinyl estradiol“do very well” with that combination of add-back therapy.

Elagolix is the most recent second-tier treatment option for these patients, and was studied in the Elaris EM-I and Elaris EM-II trials in a once-daily dose of 150 mg and a twice-daily dose of 200 mg. In Elaris EM-1, 76% of patients in the 200-mg elagolix group had a clinical response, compared with 46% in the 150-mg group and 20% in the placebo group (N Engl J Med. 2017 Jul 6. doi: 10.1056/NEJMoa1700089). However, patients should not be on elagolix at 200 mg for more than 6 months, while patients receiving elagolix at 150 mg can stay on the treatment for up to 2 years.

Patients taking elagolix also showed postmenopausal symptoms, with 24% in the 150-mg group and 46% in the 200-mg group experiencing hot flashes, compared with 9% of patients in the placebo group. While 6% of patients in the 150-mg group and 10% in the 200-mg group discontinued because of adverse events, 1% and 3% of patients in the 150-mg and 200-mg group discontinued because of hot flashes or night sweats, respectively. “Symptoms are well tolerated, far different than in comparison with leuprolide acetate and GnRH agonists,” said Dr. Miller.

There also is a benefit to how patients recover from bone mineral density (BMD) changes after remaining on elagolix, Dr. Miller noted. In patients who received elagolix for 12 months at doses of 150 mg and 200 mg, there was an increase in lumbar spine BMD recovered 6 months after discontinuation, with patients in the 150-mg group experiencing a recovery close to baseline BMD levels. Among patients who discontinued treatment, there also was a quick resumption in menses for both groups: 87% of patients in the 150 mg group and 88% of patients in the 200-mg group who discontinued treatment after 6 months had resumed menses by 2 months after discontinuation, while 95% of patients in the 150-mg and 91% in the 200-mg group who discontinued after 12 months resumed menses by 2 months after discontinuation.

Dr. Miller reported relationships with AbbVie, Allergan, Blue Seas Med Spa, Espiner Medical, Gynesonics, Halt Medical, Hologic, Karl Storz, Medtronic, and Richard Wolf in the form of consultancies, grants, speakers’ bureau appointments, stock options, royalties, and ownership interests.

ATLANTA – Patients with systemic sclerosis aged 44 years and younger in the United States now have mortality comparable to that of the general population in that age group, according to recent results presented at the annual meeting of the American College of Rheumatology.

“Mortality for scleroderma has steadily decreased in younger ages for the last 5 decades,” Ram R. Singh, MD, professor of medicine, pathology, and laboratory medicine at the University of California, Los Angeles, said in his presentation.

Using the Centers for Disease Control and Prevention’s National Vital Statistics System database, Dr. Singh and colleagues analyzed data of adults with systemic sclerosis (SSc) and identified 46,798 adults who died between 1968 and 2015. They divided the adults with and without SSc into three different age groups: 44 and younger, 45-64, and 65 and older. The researchers performed a joinpoint trend analysis, calculating the annual percent change (APC) and average APC as well as the age-standardized mortality rate (ASMR) in each age group.

In 1968, 466 deaths were attributed to SSc, compared with 1,195 deaths in 2015. Between 1968 and 2015, there was a 19% cumulative percentage increase in SSc-related deaths, compared with a 44% decrease in mortality not attributed to SSc; when the researchers analyzed the ratio of SSc-related ASMR to non-SSc-related ASMR, there was an increase of 112%, Dr. Singh said.

When analyzing the mortality of adults with SSc by age group during 1968-2015 using the CDC’s database, Dr. Singh and colleagues found 5,457 deaths in adults 44 and younger (11.7%), 18,395 deaths in adults aged 45-64 (39.3%), and 22,946 deaths in adults aged 65 and older (49.0%), compared with totals for the general population of 10.3 million deaths in adults aged 44 and younger (9.7%), 20.8 million deaths in adults 45-64 years (19.6%), and 74.8 million deaths in adults aged 65 and older (70.6%).

Over the 48-year period, there were three major trends in SSc-related ASMR, Dr. Singh noted. In the first trend period between 1968 and 1988, there was a 1.0% increase per year (95% confidence interval, 0.6%-1.4%). The second trend period, lasting until 2000, saw a 2.2% increase per year (95% CI, 1.6%-2.7%), while the SSc-related ASMR declined by 2.6% per year in the third trend period from 2001 to 2015 (95% CI, –3.1% to –2.2%).

The percentage of annual deaths for adults with SSc decreased between 1968 and 2015, from 23.4% to 5.7%, and the average APC was greater among adults aged 44 and younger with SSc (–2.2%; 95% CI, –2.4% to –2.0%) than for adults without SSc in the same age group (–1.5%; 95% CI, –1.9% to –1.1%).

There was a cumulative 60% decrease in the ASMR of adults with SSc aged 44 and younger between 1968 and 2015 from an ASMR of 1.0 per million (95% CI, 0.8%-1.2%) to an ASMR of 0.4 per million (0.3-0.5). Adults aged 45-64 years with SSc had a cumulative 20.3% decrease in ASMR over the same time period, with an ASMR of 5.9 per million in 1968 (95% CI, 5.2-6.7) and an ASMR of 4.7 per million in 2015 (95% CI, 4.2-5.2). However, adults aged 65 and older with SSc had a 187% cumulative increase in ASMR, with an ASMR of 5.4 per million in 1968 (95% CI, 4.4-6.5) and an ASMR of 15.5 per million in 2015 (95% CI, 14.3-16.6). Adults with non-SSc-related deaths between 1968 and 2015 had a 50.0% cumulative decrease in ASMR in the group aged 44 and under, a 48.0% cumulative decrease in the 45-year to 64-year-old group, and a 42.1% decrease in the 65-year-old or older group.

The ratio of SSc to non-SSc ASMRs between 1968 and 2015 in the group aged 44 and younger declined 20.0%, whereas there was a 53.1% cumulative increase in the 45- to 64-year-old group and a 395.4% cumulative increase in the 65-year-old and older group. In the oldest group, the APC increased by 3.9% each year for 33 years (95% CI, 3.7%-4.1%) before declining by 1.6% until 2015 (95% CI, –2.0 to –1.3). In contrast, the APC for adults 44 and younger never significantly increased over the 48 years, Dr. Singh noted.

“Increasing scleroderma mortality in older age could be due to improving survival and/or increasing age of onset of scleroderma,” he said.

Dr. Singh reported no conflicts of interest.

SOURCE: Yen E et al. Arthritis Rheumatol. 2019;71(suppl 10), Abstract 825.

ATLANTA – Patients with systemic sclerosis aged 44 years and younger in the United States now have mortality comparable to that of the general population in that age group, according to recent results presented at the annual meeting of the American College of Rheumatology.

“Mortality for scleroderma has steadily decreased in younger ages for the last 5 decades,” Ram R. Singh, MD, professor of medicine, pathology, and laboratory medicine at the University of California, Los Angeles, said in his presentation.

Using the Centers for Disease Control and Prevention’s National Vital Statistics System database, Dr. Singh and colleagues analyzed data of adults with systemic sclerosis (SSc) and identified 46,798 adults who died between 1968 and 2015. They divided the adults with and without SSc into three different age groups: 44 and younger, 45-64, and 65 and older. The researchers performed a joinpoint trend analysis, calculating the annual percent change (APC) and average APC as well as the age-standardized mortality rate (ASMR) in each age group.

In 1968, 466 deaths were attributed to SSc, compared with 1,195 deaths in 2015. Between 1968 and 2015, there was a 19% cumulative percentage increase in SSc-related deaths, compared with a 44% decrease in mortality not attributed to SSc; when the researchers analyzed the ratio of SSc-related ASMR to non-SSc-related ASMR, there was an increase of 112%, Dr. Singh said.

When analyzing the mortality of adults with SSc by age group during 1968-2015 using the CDC’s database, Dr. Singh and colleagues found 5,457 deaths in adults 44 and younger (11.7%), 18,395 deaths in adults aged 45-64 (39.3%), and 22,946 deaths in adults aged 65 and older (49.0%), compared with totals for the general population of 10.3 million deaths in adults aged 44 and younger (9.7%), 20.8 million deaths in adults 45-64 years (19.6%), and 74.8 million deaths in adults aged 65 and older (70.6%).

Over the 48-year period, there were three major trends in SSc-related ASMR, Dr. Singh noted. In the first trend period between 1968 and 1988, there was a 1.0% increase per year (95% confidence interval, 0.6%-1.4%). The second trend period, lasting until 2000, saw a 2.2% increase per year (95% CI, 1.6%-2.7%), while the SSc-related ASMR declined by 2.6% per year in the third trend period from 2001 to 2015 (95% CI, –3.1% to –2.2%).

The percentage of annual deaths for adults with SSc decreased between 1968 and 2015, from 23.4% to 5.7%, and the average APC was greater among adults aged 44 and younger with SSc (–2.2%; 95% CI, –2.4% to –2.0%) than for adults without SSc in the same age group (–1.5%; 95% CI, –1.9% to –1.1%).

There was a cumulative 60% decrease in the ASMR of adults with SSc aged 44 and younger between 1968 and 2015 from an ASMR of 1.0 per million (95% CI, 0.8%-1.2%) to an ASMR of 0.4 per million (0.3-0.5). Adults aged 45-64 years with SSc had a cumulative 20.3% decrease in ASMR over the same time period, with an ASMR of 5.9 per million in 1968 (95% CI, 5.2-6.7) and an ASMR of 4.7 per million in 2015 (95% CI, 4.2-5.2). However, adults aged 65 and older with SSc had a 187% cumulative increase in ASMR, with an ASMR of 5.4 per million in 1968 (95% CI, 4.4-6.5) and an ASMR of 15.5 per million in 2015 (95% CI, 14.3-16.6). Adults with non-SSc-related deaths between 1968 and 2015 had a 50.0% cumulative decrease in ASMR in the group aged 44 and under, a 48.0% cumulative decrease in the 45-year to 64-year-old group, and a 42.1% decrease in the 65-year-old or older group.

The ratio of SSc to non-SSc ASMRs between 1968 and 2015 in the group aged 44 and younger declined 20.0%, whereas there was a 53.1% cumulative increase in the 45- to 64-year-old group and a 395.4% cumulative increase in the 65-year-old and older group. In the oldest group, the APC increased by 3.9% each year for 33 years (95% CI, 3.7%-4.1%) before declining by 1.6% until 2015 (95% CI, –2.0 to –1.3). In contrast, the APC for adults 44 and younger never significantly increased over the 48 years, Dr. Singh noted.

“Increasing scleroderma mortality in older age could be due to improving survival and/or increasing age of onset of scleroderma,” he said.

Dr. Singh reported no conflicts of interest.

SOURCE: Yen E et al. Arthritis Rheumatol. 2019;71(suppl 10), Abstract 825.

ATLANTA – Patients with systemic sclerosis aged 44 years and younger in the United States now have mortality comparable to that of the general population in that age group, according to recent results presented at the annual meeting of the American College of Rheumatology.

“Mortality for scleroderma has steadily decreased in younger ages for the last 5 decades,” Ram R. Singh, MD, professor of medicine, pathology, and laboratory medicine at the University of California, Los Angeles, said in his presentation.

Using the Centers for Disease Control and Prevention’s National Vital Statistics System database, Dr. Singh and colleagues analyzed data of adults with systemic sclerosis (SSc) and identified 46,798 adults who died between 1968 and 2015. They divided the adults with and without SSc into three different age groups: 44 and younger, 45-64, and 65 and older. The researchers performed a joinpoint trend analysis, calculating the annual percent change (APC) and average APC as well as the age-standardized mortality rate (ASMR) in each age group.

In 1968, 466 deaths were attributed to SSc, compared with 1,195 deaths in 2015. Between 1968 and 2015, there was a 19% cumulative percentage increase in SSc-related deaths, compared with a 44% decrease in mortality not attributed to SSc; when the researchers analyzed the ratio of SSc-related ASMR to non-SSc-related ASMR, there was an increase of 112%, Dr. Singh said.

When analyzing the mortality of adults with SSc by age group during 1968-2015 using the CDC’s database, Dr. Singh and colleagues found 5,457 deaths in adults 44 and younger (11.7%), 18,395 deaths in adults aged 45-64 (39.3%), and 22,946 deaths in adults aged 65 and older (49.0%), compared with totals for the general population of 10.3 million deaths in adults aged 44 and younger (9.7%), 20.8 million deaths in adults 45-64 years (19.6%), and 74.8 million deaths in adults aged 65 and older (70.6%).

Over the 48-year period, there were three major trends in SSc-related ASMR, Dr. Singh noted. In the first trend period between 1968 and 1988, there was a 1.0% increase per year (95% confidence interval, 0.6%-1.4%). The second trend period, lasting until 2000, saw a 2.2% increase per year (95% CI, 1.6%-2.7%), while the SSc-related ASMR declined by 2.6% per year in the third trend period from 2001 to 2015 (95% CI, –3.1% to –2.2%).

The percentage of annual deaths for adults with SSc decreased between 1968 and 2015, from 23.4% to 5.7%, and the average APC was greater among adults aged 44 and younger with SSc (–2.2%; 95% CI, –2.4% to –2.0%) than for adults without SSc in the same age group (–1.5%; 95% CI, –1.9% to –1.1%).

There was a cumulative 60% decrease in the ASMR of adults with SSc aged 44 and younger between 1968 and 2015 from an ASMR of 1.0 per million (95% CI, 0.8%-1.2%) to an ASMR of 0.4 per million (0.3-0.5). Adults aged 45-64 years with SSc had a cumulative 20.3% decrease in ASMR over the same time period, with an ASMR of 5.9 per million in 1968 (95% CI, 5.2-6.7) and an ASMR of 4.7 per million in 2015 (95% CI, 4.2-5.2). However, adults aged 65 and older with SSc had a 187% cumulative increase in ASMR, with an ASMR of 5.4 per million in 1968 (95% CI, 4.4-6.5) and an ASMR of 15.5 per million in 2015 (95% CI, 14.3-16.6). Adults with non-SSc-related deaths between 1968 and 2015 had a 50.0% cumulative decrease in ASMR in the group aged 44 and under, a 48.0% cumulative decrease in the 45-year to 64-year-old group, and a 42.1% decrease in the 65-year-old or older group.

The ratio of SSc to non-SSc ASMRs between 1968 and 2015 in the group aged 44 and younger declined 20.0%, whereas there was a 53.1% cumulative increase in the 45- to 64-year-old group and a 395.4% cumulative increase in the 65-year-old and older group. In the oldest group, the APC increased by 3.9% each year for 33 years (95% CI, 3.7%-4.1%) before declining by 1.6% until 2015 (95% CI, –2.0 to –1.3). In contrast, the APC for adults 44 and younger never significantly increased over the 48 years, Dr. Singh noted.

“Increasing scleroderma mortality in older age could be due to improving survival and/or increasing age of onset of scleroderma,” he said.

Dr. Singh reported no conflicts of interest.

SOURCE: Yen E et al. Arthritis Rheumatol. 2019;71(suppl 10), Abstract 825.

PHILADELPHIA – Postmenopausal women are at risk of numerous medical conditions after the onset of menopause, but many ob.gyns feel uncomfortable treating those patients, according to a keynote speaker at the annual meeting of the American Society for Reproductive Medicine.

Jeff Craven/MDedge News

The population of women entering menopause continues to rise, and they are at risk for developing chronic diseases about a decade after the onset of menopause, said Rogerio A. Lobo, MD, professor of obstetrics and gynecology at Columbia University, New York.

“For me, from a primary care perspective, there’s a major opportunity for all of us providers at the onset of menopause to identify risks and initiate preventive strategies,” he said.

These newly menopausal women are at risk for diseases across multiple specialty areas, which include obesity, metabolic syndrome, diabetes, cardiovascular disease, osteoporosis, chronic arthritis, dementia, cognitive decline, depression, and cancer. “My focus along these lines is really longevity, reduction in mortality as well as quality of life,” said Dr. Lobo.

Understanding of the benefits of estrogen therapy for postmenopausal women began with work in two studies in the 1990s. One paper by Meir J. Stampfer, MD, and associates on 15 studies examining the effects of hormone therapy on coronary heart disease (CHD) found that the relative risk of estrogen therapy on the disease was 0.50 (95% confidence interval, 0.43-0.56) after adjusting for only prospective and angiographic studies (Prev Med. 1991;20[1]:47-63).

A second paper by Deborah Grady, MD, MPH, and associates found that hormone therapy with estrogen plus progestin decreased the risk of CHD and hip fracture in women but increased the risk of endometrial and breast cancer, and carried a recommendation for using estrogen plus progestin for women who have received a hysterectomy or who are at high risk for CHD (Ann Intern Med. 1992 Dec 15;117[12]:1016-37).

In the early 2000s, data from the Women’s Health Initiative (WHI) began to show a different story: Therapy with estrogen plus progestin was shown to carry risks of early harm in postmenopausal women, and one study by JoAnn E. Manson, MD, DrPH, and associates had a hazard ratio of 1.24 (nominal 95% confidence interval, 1.00-1.54) for CHD in postmenopausal women aged 50-79 years receiving the combined therapy (N Engl J Med. 2003;349:523-34).

The confidence intervals were later adjusted so the association was not significant, but the results led to conclusions that hormone therapy was harmful to women and increased risk of breast cancer, declining cognition, and dementia, as well as cardiovascular diseases such as coronary disease, stroke and thrombosis.

“That was the dogma for many people to this day, but it was clearly a rush to judgment,” said Dr. Lobo. “More harm than good was done for the field.”

The contradictory findings from the WHI and other studies may be explained by the timing of hormone therapy, Dr. Lobo explained. In the ELITE trial, 643 postmenopausal women, stratified into early-postmenopausal (less than 6 years) and late-postmenopausal (equal to or greater than 10 years) groups, received 1 mg of daily oral 17-beta-estradiol with 45 mg of progesterone vaginal gel or placebo. Researchers found that it was beneficial for preventing the progression of subclinical atherosclerosis when therapy was initiated in early but not in late menopause (N Eng J Med. 2016; 374:1221-31).

Estrogen also has benefits for the brain, and might help improve rates of cognitive decline and Alzheimer’s disease in postmenopausal women, Dr. Lobo said. Of the 1,768 women in the Cache County Study who described their use of hormone therapy after menopause, 176 women developed Alzheimer’s; however, use of hormone therapy within 5 years of menopause was associated with a 30% reduced risk of Alzheimer’s (95% confidence interval, 0.49-0.99) and had better benefits for long-term use up to 10 years. But this effect was not present in women who started hormone therapy 5 years or more after onset of menopause (Neurology. 2012 Oct 30. doi: 10.1212/WNL.0b013e318271f823).

Clinicians also should look at the risk of hormone therapy in terms of absolute real risk rather than relative risk. “In WHI, even though many of these events were not statistically significant, even if they assumed they were, the absolute numbers were 7-8 events per 10,000 women per year,” he said. “Those, according to WHI, are rare events if they’re even true.”

“For breast cancer, which is a big concern a lot of women have, endogenous risk factors are much higher than what hormones do,” he added.

Yet clinicians continue to act on data from the WHI, Dr. Lobo noted. In fact, many ob.gyns. report that they are uncomfortable treating women with symptoms associated with menopause.

“Post WHI, we have lost at least a generation of providers who do not deal with menopause,” he added. “Three out of four women who seek help for symptoms don’t receive it. The practice of menopause has largely disappeared from for many, many practices.”

The American Society for Reproductive Medicine used to have a “menopause day,” but the society no longer offers a track for menopause, Dr. Lobo said. One solution aimed at addressing the absence of training might be a menopause curriculum for ob.gyn. residents to help them initiate prevention strategies for postmenopausal women and have the confidence to manage this patient population. Dr. Lobo cited one study from Johns Hopkins where ob.gyn. residents underwent a 2-year menopause medicine curriculum and scored significantly higher on posttest scores after completing the program (78.7% vs. 57.3%; P less than .05). After the curriculum, 85.7% also reported they were more comfortable treating patients with menopause (Menopause. 2016 Mar. 23[3]:275-9).

Work also needs to be done on the front of understanding which hormone therapies are most effective for postmenopausal women. While there is currently no one hormone therapy to specifically recommend, in the future, pharmacogenetics and genetic or molecular risk analyses will play a role in knowing which products to prescribe. “It can be done, to be able to have a clear path for longevity and improved quality of life,” Dr. Lobo said.

Dr. Lobo reported serving as a consultant to Amgen, Mithra, Sojournix, and TherapeuticsMD. In addition, his institution is receiving support from Bayer and the National Institutes of Health for a clinical trial.

PHILADELPHIA – Postmenopausal women are at risk of numerous medical conditions after the onset of menopause, but many ob.gyns feel uncomfortable treating those patients, according to a keynote speaker at the annual meeting of the American Society for Reproductive Medicine.

Jeff Craven/MDedge News

The population of women entering menopause continues to rise, and they are at risk for developing chronic diseases about a decade after the onset of menopause, said Rogerio A. Lobo, MD, professor of obstetrics and gynecology at Columbia University, New York.

“For me, from a primary care perspective, there’s a major opportunity for all of us providers at the onset of menopause to identify risks and initiate preventive strategies,” he said.

These newly menopausal women are at risk for diseases across multiple specialty areas, which include obesity, metabolic syndrome, diabetes, cardiovascular disease, osteoporosis, chronic arthritis, dementia, cognitive decline, depression, and cancer. “My focus along these lines is really longevity, reduction in mortality as well as quality of life,” said Dr. Lobo.

Understanding of the benefits of estrogen therapy for postmenopausal women began with work in two studies in the 1990s. One paper by Meir J. Stampfer, MD, and associates on 15 studies examining the effects of hormone therapy on coronary heart disease (CHD) found that the relative risk of estrogen therapy on the disease was 0.50 (95% confidence interval, 0.43-0.56) after adjusting for only prospective and angiographic studies (Prev Med. 1991;20[1]:47-63).

A second paper by Deborah Grady, MD, MPH, and associates found that hormone therapy with estrogen plus progestin decreased the risk of CHD and hip fracture in women but increased the risk of endometrial and breast cancer, and carried a recommendation for using estrogen plus progestin for women who have received a hysterectomy or who are at high risk for CHD (Ann Intern Med. 1992 Dec 15;117[12]:1016-37).

In the early 2000s, data from the Women’s Health Initiative (WHI) began to show a different story: Therapy with estrogen plus progestin was shown to carry risks of early harm in postmenopausal women, and one study by JoAnn E. Manson, MD, DrPH, and associates had a hazard ratio of 1.24 (nominal 95% confidence interval, 1.00-1.54) for CHD in postmenopausal women aged 50-79 years receiving the combined therapy (N Engl J Med. 2003;349:523-34).

The confidence intervals were later adjusted so the association was not significant, but the results led to conclusions that hormone therapy was harmful to women and increased risk of breast cancer, declining cognition, and dementia, as well as cardiovascular diseases such as coronary disease, stroke and thrombosis.

“That was the dogma for many people to this day, but it was clearly a rush to judgment,” said Dr. Lobo. “More harm than good was done for the field.”

The contradictory findings from the WHI and other studies may be explained by the timing of hormone therapy, Dr. Lobo explained. In the ELITE trial, 643 postmenopausal women, stratified into early-postmenopausal (less than 6 years) and late-postmenopausal (equal to or greater than 10 years) groups, received 1 mg of daily oral 17-beta-estradiol with 45 mg of progesterone vaginal gel or placebo. Researchers found that it was beneficial for preventing the progression of subclinical atherosclerosis when therapy was initiated in early but not in late menopause (N Eng J Med. 2016; 374:1221-31).

Estrogen also has benefits for the brain, and might help improve rates of cognitive decline and Alzheimer’s disease in postmenopausal women, Dr. Lobo said. Of the 1,768 women in the Cache County Study who described their use of hormone therapy after menopause, 176 women developed Alzheimer’s; however, use of hormone therapy within 5 years of menopause was associated with a 30% reduced risk of Alzheimer’s (95% confidence interval, 0.49-0.99) and had better benefits for long-term use up to 10 years. But this effect was not present in women who started hormone therapy 5 years or more after onset of menopause (Neurology. 2012 Oct 30. doi: 10.1212/WNL.0b013e318271f823).

Clinicians also should look at the risk of hormone therapy in terms of absolute real risk rather than relative risk. “In WHI, even though many of these events were not statistically significant, even if they assumed they were, the absolute numbers were 7-8 events per 10,000 women per year,” he said. “Those, according to WHI, are rare events if they’re even true.”

“For breast cancer, which is a big concern a lot of women have, endogenous risk factors are much higher than what hormones do,” he added.

Yet clinicians continue to act on data from the WHI, Dr. Lobo noted. In fact, many ob.gyns. report that they are uncomfortable treating women with symptoms associated with menopause.

“Post WHI, we have lost at least a generation of providers who do not deal with menopause,” he added. “Three out of four women who seek help for symptoms don’t receive it. The practice of menopause has largely disappeared from for many, many practices.”

The American Society for Reproductive Medicine used to have a “menopause day,” but the society no longer offers a track for menopause, Dr. Lobo said. One solution aimed at addressing the absence of training might be a menopause curriculum for ob.gyn. residents to help them initiate prevention strategies for postmenopausal women and have the confidence to manage this patient population. Dr. Lobo cited one study from Johns Hopkins where ob.gyn. residents underwent a 2-year menopause medicine curriculum and scored significantly higher on posttest scores after completing the program (78.7% vs. 57.3%; P less than .05). After the curriculum, 85.7% also reported they were more comfortable treating patients with menopause (Menopause. 2016 Mar. 23[3]:275-9).

Work also needs to be done on the front of understanding which hormone therapies are most effective for postmenopausal women. While there is currently no one hormone therapy to specifically recommend, in the future, pharmacogenetics and genetic or molecular risk analyses will play a role in knowing which products to prescribe. “It can be done, to be able to have a clear path for longevity and improved quality of life,” Dr. Lobo said.

Dr. Lobo reported serving as a consultant to Amgen, Mithra, Sojournix, and TherapeuticsMD. In addition, his institution is receiving support from Bayer and the National Institutes of Health for a clinical trial.

PHILADELPHIA – Postmenopausal women are at risk of numerous medical conditions after the onset of menopause, but many ob.gyns feel uncomfortable treating those patients, according to a keynote speaker at the annual meeting of the American Society for Reproductive Medicine.

Jeff Craven/MDedge News

The population of women entering menopause continues to rise, and they are at risk for developing chronic diseases about a decade after the onset of menopause, said Rogerio A. Lobo, MD, professor of obstetrics and gynecology at Columbia University, New York.

“For me, from a primary care perspective, there’s a major opportunity for all of us providers at the onset of menopause to identify risks and initiate preventive strategies,” he said.

These newly menopausal women are at risk for diseases across multiple specialty areas, which include obesity, metabolic syndrome, diabetes, cardiovascular disease, osteoporosis, chronic arthritis, dementia, cognitive decline, depression, and cancer. “My focus along these lines is really longevity, reduction in mortality as well as quality of life,” said Dr. Lobo.

Understanding of the benefits of estrogen therapy for postmenopausal women began with work in two studies in the 1990s. One paper by Meir J. Stampfer, MD, and associates on 15 studies examining the effects of hormone therapy on coronary heart disease (CHD) found that the relative risk of estrogen therapy on the disease was 0.50 (95% confidence interval, 0.43-0.56) after adjusting for only prospective and angiographic studies (Prev Med. 1991;20[1]:47-63).

A second paper by Deborah Grady, MD, MPH, and associates found that hormone therapy with estrogen plus progestin decreased the risk of CHD and hip fracture in women but increased the risk of endometrial and breast cancer, and carried a recommendation for using estrogen plus progestin for women who have received a hysterectomy or who are at high risk for CHD (Ann Intern Med. 1992 Dec 15;117[12]:1016-37).

In the early 2000s, data from the Women’s Health Initiative (WHI) began to show a different story: Therapy with estrogen plus progestin was shown to carry risks of early harm in postmenopausal women, and one study by JoAnn E. Manson, MD, DrPH, and associates had a hazard ratio of 1.24 (nominal 95% confidence interval, 1.00-1.54) for CHD in postmenopausal women aged 50-79 years receiving the combined therapy (N Engl J Med. 2003;349:523-34).

The confidence intervals were later adjusted so the association was not significant, but the results led to conclusions that hormone therapy was harmful to women and increased risk of breast cancer, declining cognition, and dementia, as well as cardiovascular diseases such as coronary disease, stroke and thrombosis.

“That was the dogma for many people to this day, but it was clearly a rush to judgment,” said Dr. Lobo. “More harm than good was done for the field.”

The contradictory findings from the WHI and other studies may be explained by the timing of hormone therapy, Dr. Lobo explained. In the ELITE trial, 643 postmenopausal women, stratified into early-postmenopausal (less than 6 years) and late-postmenopausal (equal to or greater than 10 years) groups, received 1 mg of daily oral 17-beta-estradiol with 45 mg of progesterone vaginal gel or placebo. Researchers found that it was beneficial for preventing the progression of subclinical atherosclerosis when therapy was initiated in early but not in late menopause (N Eng J Med. 2016; 374:1221-31).

Estrogen also has benefits for the brain, and might help improve rates of cognitive decline and Alzheimer’s disease in postmenopausal women, Dr. Lobo said. Of the 1,768 women in the Cache County Study who described their use of hormone therapy after menopause, 176 women developed Alzheimer’s; however, use of hormone therapy within 5 years of menopause was associated with a 30% reduced risk of Alzheimer’s (95% confidence interval, 0.49-0.99) and had better benefits for long-term use up to 10 years. But this effect was not present in women who started hormone therapy 5 years or more after onset of menopause (Neurology. 2012 Oct 30. doi: 10.1212/WNL.0b013e318271f823).

Clinicians also should look at the risk of hormone therapy in terms of absolute real risk rather than relative risk. “In WHI, even though many of these events were not statistically significant, even if they assumed they were, the absolute numbers were 7-8 events per 10,000 women per year,” he said. “Those, according to WHI, are rare events if they’re even true.”

“For breast cancer, which is a big concern a lot of women have, endogenous risk factors are much higher than what hormones do,” he added.

Yet clinicians continue to act on data from the WHI, Dr. Lobo noted. In fact, many ob.gyns. report that they are uncomfortable treating women with symptoms associated with menopause.

“Post WHI, we have lost at least a generation of providers who do not deal with menopause,” he added. “Three out of four women who seek help for symptoms don’t receive it. The practice of menopause has largely disappeared from for many, many practices.”

The American Society for Reproductive Medicine used to have a “menopause day,” but the society no longer offers a track for menopause, Dr. Lobo said. One solution aimed at addressing the absence of training might be a menopause curriculum for ob.gyn. residents to help them initiate prevention strategies for postmenopausal women and have the confidence to manage this patient population. Dr. Lobo cited one study from Johns Hopkins where ob.gyn. residents underwent a 2-year menopause medicine curriculum and scored significantly higher on posttest scores after completing the program (78.7% vs. 57.3%; P less than .05). After the curriculum, 85.7% also reported they were more comfortable treating patients with menopause (Menopause. 2016 Mar. 23[3]:275-9).

Work also needs to be done on the front of understanding which hormone therapies are most effective for postmenopausal women. While there is currently no one hormone therapy to specifically recommend, in the future, pharmacogenetics and genetic or molecular risk analyses will play a role in knowing which products to prescribe. “It can be done, to be able to have a clear path for longevity and improved quality of life,” Dr. Lobo said.

Dr. Lobo reported serving as a consultant to Amgen, Mithra, Sojournix, and TherapeuticsMD. In addition, his institution is receiving support from Bayer and the National Institutes of Health for a clinical trial.

Almost all of the patient assistance programs funded by independent charities for subsidizing prescription medications exclude patients without insurance, a cross-sectional analysis has shown.

Of 274 patient assistance programs analyzed from six independent charities, 267 (97%) listed insurance coverage as an eligibility requirement for their program, according to So-Yeon Kang, MPH, MBA, a PhD student at Johns Hopkins University, Baltimore, and colleagues.

Out-of-pocket prescription costs for Medicare Part D plans can cost “thousands of dollars” because of higher coinsurance rates and no catastrophic cap on the program, the researchers noted in JAMA.

“For this reason, independent charity foundations offering patient assistance programs to these patients are entitled to receive tax-deductible donations from pharmaceutical companies,” they wrote. “However, the findings from this study suggest that several features of the programs may limit their usefulness to financially needy patients and bolster the use of expensive drugs.”

The researchers examined the 274 patient assistance programs funded by the CancerCare Co-Payment Assistance Foundation, Good Days, the HealthWell Foundation, the Patient Access Network Foundation, Patient Advocate Foundation Co-Pay Relief, and Patient Services Incorporated. Copayment assistance alone was provided by 168 programs, 90 programs offered assistance with copayments and health insurance premiums, and 9 programs provided assistance to subsidize health insurance premiums only.

Cancer or cancer-related treatments were covered by 41% of programs, and 34% provided assistance for genetic or rare diseases.

In 2017, the six charities spent an average of 86% of their revenue on patient expenditures: They had a total revenue of between $24 million and $532 million, while the expenditures for patient assistance ranged from $24 million and $353 million. With regard to eligibility, the income limit that was most common was 500% of the federal poverty level.

The researchers also studied which of 18 drugs were covered by assistance programs. They found that brand-name prescriptions were covered by a mean of 3.1 assistance programs, compared with a mean of 1.2 programs that covered a generic version of each drug. Of the 18 drugs studied, 12 drugs (67%) were in protected classes and therefore covered by Medicare Part D. Prescription drugs that were covered were more likely to be expensive, compared with drugs that were not covered (median annual cost of $1,157, versus $367).

The researchers noted several limitations of the study, such the inability to correlate the programs with drug spending, assuming that generic substitution was always possible. In addition, the analysis of drug use was limited to two charity foundations.

In a related editorial, Katherine L. Kraschel and Gregory D. Curfman, MD, wrote that some patient assistance programs might be violating federal law.

“Coupled with recent enforcement activity by the Department of Justice, the data reported by Kang et al. suggest that some programs may warrant continued regulatory scrutiny and enforcement,” wrote Ms. Kraschel, executive director of the Solomon Center for Health Law & Policy at Yale University Law School, New Haven, Conn., and Dr. Curfman, deputy editor of JAMA in Chicago (JAMA. 2019;322[5]:405-6).

In addition, the Office of Inspector General created a special advisory bulletin in 2014 that clarifies how pharmaceutical companies should comply with the Anti-Kickback Statute within a patient assistance program. This guidance states that pharmaceutical companies should make assistance available to all products, rather than simply high-cost or specialty drugs, which pharmaceutical companies have not consistently followed, Ms. Kraschel and Dr. Curfman explained.

To help patients and the health care system, the authors recommended the Office of the Inspector General implement stronger restrictions for pharmaceutical companies contributing to patient assistance programs and develop reporting requirements for transparency purposes.

“The extent to which patient assistance programs violate tax exemption standards that prohibit private benefit that does not further its charitable purpose and is intentionally aimed to benefit the pharmaceutical companies warrants further scrutiny,” Ms. Kraschel and Dr. Curfman wrote. “It is particularly egregious that the payments made from pharmaceutical companies to patient assistance programs may be illegal yet simultaneously tax deductible.”

The study was funded by Arnold Ventures. The authors of the study and the editorial reported no relevant conflicts of interest.

SOURCE: Kang S-Y et al. JAMA. 2019;322(5):422-9.

Almost all of the patient assistance programs funded by independent charities for subsidizing prescription medications exclude patients without insurance, a cross-sectional analysis has shown.

Of 274 patient assistance programs analyzed from six independent charities, 267 (97%) listed insurance coverage as an eligibility requirement for their program, according to So-Yeon Kang, MPH, MBA, a PhD student at Johns Hopkins University, Baltimore, and colleagues.

Out-of-pocket prescription costs for Medicare Part D plans can cost “thousands of dollars” because of higher coinsurance rates and no catastrophic cap on the program, the researchers noted in JAMA.

“For this reason, independent charity foundations offering patient assistance programs to these patients are entitled to receive tax-deductible donations from pharmaceutical companies,” they wrote. “However, the findings from this study suggest that several features of the programs may limit their usefulness to financially needy patients and bolster the use of expensive drugs.”

The researchers examined the 274 patient assistance programs funded by the CancerCare Co-Payment Assistance Foundation, Good Days, the HealthWell Foundation, the Patient Access Network Foundation, Patient Advocate Foundation Co-Pay Relief, and Patient Services Incorporated. Copayment assistance alone was provided by 168 programs, 90 programs offered assistance with copayments and health insurance premiums, and 9 programs provided assistance to subsidize health insurance premiums only.

Cancer or cancer-related treatments were covered by 41% of programs, and 34% provided assistance for genetic or rare diseases.

In 2017, the six charities spent an average of 86% of their revenue on patient expenditures: They had a total revenue of between $24 million and $532 million, while the expenditures for patient assistance ranged from $24 million and $353 million. With regard to eligibility, the income limit that was most common was 500% of the federal poverty level.

The researchers also studied which of 18 drugs were covered by assistance programs. They found that brand-name prescriptions were covered by a mean of 3.1 assistance programs, compared with a mean of 1.2 programs that covered a generic version of each drug. Of the 18 drugs studied, 12 drugs (67%) were in protected classes and therefore covered by Medicare Part D. Prescription drugs that were covered were more likely to be expensive, compared with drugs that were not covered (median annual cost of $1,157, versus $367).

The researchers noted several limitations of the study, such the inability to correlate the programs with drug spending, assuming that generic substitution was always possible. In addition, the analysis of drug use was limited to two charity foundations.

In a related editorial, Katherine L. Kraschel and Gregory D. Curfman, MD, wrote that some patient assistance programs might be violating federal law.

“Coupled with recent enforcement activity by the Department of Justice, the data reported by Kang et al. suggest that some programs may warrant continued regulatory scrutiny and enforcement,” wrote Ms. Kraschel, executive director of the Solomon Center for Health Law & Policy at Yale University Law School, New Haven, Conn., and Dr. Curfman, deputy editor of JAMA in Chicago (JAMA. 2019;322[5]:405-6).

In addition, the Office of Inspector General created a special advisory bulletin in 2014 that clarifies how pharmaceutical companies should comply with the Anti-Kickback Statute within a patient assistance program. This guidance states that pharmaceutical companies should make assistance available to all products, rather than simply high-cost or specialty drugs, which pharmaceutical companies have not consistently followed, Ms. Kraschel and Dr. Curfman explained.

To help patients and the health care system, the authors recommended the Office of the Inspector General implement stronger restrictions for pharmaceutical companies contributing to patient assistance programs and develop reporting requirements for transparency purposes.

“The extent to which patient assistance programs violate tax exemption standards that prohibit private benefit that does not further its charitable purpose and is intentionally aimed to benefit the pharmaceutical companies warrants further scrutiny,” Ms. Kraschel and Dr. Curfman wrote. “It is particularly egregious that the payments made from pharmaceutical companies to patient assistance programs may be illegal yet simultaneously tax deductible.”

The study was funded by Arnold Ventures. The authors of the study and the editorial reported no relevant conflicts of interest.

SOURCE: Kang S-Y et al. JAMA. 2019;322(5):422-9.

Almost all of the patient assistance programs funded by independent charities for subsidizing prescription medications exclude patients without insurance, a cross-sectional analysis has shown.

Of 274 patient assistance programs analyzed from six independent charities, 267 (97%) listed insurance coverage as an eligibility requirement for their program, according to So-Yeon Kang, MPH, MBA, a PhD student at Johns Hopkins University, Baltimore, and colleagues.

Out-of-pocket prescription costs for Medicare Part D plans can cost “thousands of dollars” because of higher coinsurance rates and no catastrophic cap on the program, the researchers noted in JAMA.

“For this reason, independent charity foundations offering patient assistance programs to these patients are entitled to receive tax-deductible donations from pharmaceutical companies,” they wrote. “However, the findings from this study suggest that several features of the programs may limit their usefulness to financially needy patients and bolster the use of expensive drugs.”

The researchers examined the 274 patient assistance programs funded by the CancerCare Co-Payment Assistance Foundation, Good Days, the HealthWell Foundation, the Patient Access Network Foundation, Patient Advocate Foundation Co-Pay Relief, and Patient Services Incorporated. Copayment assistance alone was provided by 168 programs, 90 programs offered assistance with copayments and health insurance premiums, and 9 programs provided assistance to subsidize health insurance premiums only.

Cancer or cancer-related treatments were covered by 41% of programs, and 34% provided assistance for genetic or rare diseases.

In 2017, the six charities spent an average of 86% of their revenue on patient expenditures: They had a total revenue of between $24 million and $532 million, while the expenditures for patient assistance ranged from $24 million and $353 million. With regard to eligibility, the income limit that was most common was 500% of the federal poverty level.

The researchers also studied which of 18 drugs were covered by assistance programs. They found that brand-name prescriptions were covered by a mean of 3.1 assistance programs, compared with a mean of 1.2 programs that covered a generic version of each drug. Of the 18 drugs studied, 12 drugs (67%) were in protected classes and therefore covered by Medicare Part D. Prescription drugs that were covered were more likely to be expensive, compared with drugs that were not covered (median annual cost of $1,157, versus $367).

The researchers noted several limitations of the study, such the inability to correlate the programs with drug spending, assuming that generic substitution was always possible. In addition, the analysis of drug use was limited to two charity foundations.

In a related editorial, Katherine L. Kraschel and Gregory D. Curfman, MD, wrote that some patient assistance programs might be violating federal law.

“Coupled with recent enforcement activity by the Department of Justice, the data reported by Kang et al. suggest that some programs may warrant continued regulatory scrutiny and enforcement,” wrote Ms. Kraschel, executive director of the Solomon Center for Health Law & Policy at Yale University Law School, New Haven, Conn., and Dr. Curfman, deputy editor of JAMA in Chicago (JAMA. 2019;322[5]:405-6).

In addition, the Office of Inspector General created a special advisory bulletin in 2014 that clarifies how pharmaceutical companies should comply with the Anti-Kickback Statute within a patient assistance program. This guidance states that pharmaceutical companies should make assistance available to all products, rather than simply high-cost or specialty drugs, which pharmaceutical companies have not consistently followed, Ms. Kraschel and Dr. Curfman explained.

To help patients and the health care system, the authors recommended the Office of the Inspector General implement stronger restrictions for pharmaceutical companies contributing to patient assistance programs and develop reporting requirements for transparency purposes.

“The extent to which patient assistance programs violate tax exemption standards that prohibit private benefit that does not further its charitable purpose and is intentionally aimed to benefit the pharmaceutical companies warrants further scrutiny,” Ms. Kraschel and Dr. Curfman wrote. “It is particularly egregious that the payments made from pharmaceutical companies to patient assistance programs may be illegal yet simultaneously tax deductible.”

The study was funded by Arnold Ventures. The authors of the study and the editorial reported no relevant conflicts of interest.

SOURCE: Kang S-Y et al. JAMA. 2019;322(5):422-9.

ATLANTA – Patients with nonradiographic axial spondyloarthritis who received secukinumab with or without loading doses showed improvements in physical function, quality of life, inflammation, and other disease signs and symptoms, according to results from a phase 3 study presented at the annual meeting of the American College of Rheumatology.

Jeff Craven/MDedge News

For patients with nonradiographic axial spondyloarthritis in the double-blind, randomized, placebo-controlled PREVENT trial, these benefits persisted up to 52 weeks, Atul A. Deodhar, MD, professor of medicine in the division of arthritis and rheumatic diseases at Oregon Health & Science University, Portland, said in his presentation.

“This is the largest study done for a biologic agent in nonradiographic axial spondyloarthritis,” Dr. Deodhar said. The trial enrolled 185 patients who received subcutaneous secukinumab (Cosentyx) at a dose of 150 mg, 184 patients who received the medication without a loading dose, and 186 patients who received placebo.

Patients were included if they were aged at least 18 years with 6 months or more of inflammatory back pain, had objective signs of inflammation (sacroiliitis on MRI and/or C-reactive protein [CRP] at 5.0 mg/dL or higher), had active disease and spinal pain according to the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), had total back pain with a visual analog scale of 40 mm or greater, and had not received a tumor necrosis factor inhibitor (TNFi) or had an inadequate response to no more than one TNFi. Patients were also stratified by inflammation measured on MRI and CRP. A little more than half of the patients in each group were women, and at baseline their mean age was 39 years, with a mean symptom duration of more than 8 years and mean Ankylosing Spondylitis Disease Activity Score of 3.5-3.7.

The primary endpoint was at least 40% improvement in Assessment of Spondyloarthritis International Society response criteria (ASAS40) at 16 weeks to meet European Union regulatory requirements and at 52 weeks for the Food and Drug Administration. Escape to open-label secukinumab or standard of care was permitted any time after week 20 for patients deemed to have inadequate response based on clinical judgment of disease activity by the investigator and patient; at 52 weeks, the trial became open label and patients in the placebo group could begin secukinumab or standard of care. The U.S. and European Union analyses were performed independently, with the European analysis including only secukinumab with loading doses and the U.S. analysis including secukinumab without loading.

At 16 weeks, an analysis of the overall population showed that 40.8% of patients in the secukinumab nonloading group had an ASAS40 response, compared with 40.0% in those who got a loading dose and 28.0% with placebo (P less than .05 for both). Among the 90% of patients who were TNFi naive, ASAS40 responses occurred in 42.2% of patients in the nonloading group, 41.5% who received a loading dose, and 29.2% with placebo (P less than .05 for both). ASAS40 response rates persisted at 52 weeks for patients in the nonloading (39.8%), loading (35.4%), and placebo (19.9%) groups (P less than .05).

Over the same time period, the least-square mean changes in total BASDAI score improved from baseline by 2.43 in the nonloading group, 2.35 in the loading group, and 1.46 in the placebo group (P less than .05). The percentage of patients who had 50% or greater improvement in BASDAI was 37% in both treatment groups, compared with 21% with placebo (P less than .05).

Function score as measured by the Bath Ankylosing Spondylitis Functional Index also showed significantly greater improvements at 16 weeks for both loading and nonloading patients versus placebo (–1.75 and ­–1.64 vs. –1.01; P less than .05). Treatment with or without a loading dose led to significant reductions in sacroiliac joint edema on MRI and high-sensitivity CRP. The percentage patients who met ASAS partial remission criteria were significantly higher in the loading (21.6%) and nonloading (21.2%) groups, compared with placebo (7.0%; P less than .05).

Physical function and quality of life assessments at 16 weeks using the 36-item Short Form Health Survey physical component score and the Ankylosing Spondylitis Quality of Life questionnaire showed significant improvements both with and without a loading dose.

There were no new safety concerns with secukinumab that arose in the trial, Dr. Deodhar said.

Dr. Deodhar admitted the placebo effect was high in the PREVENT study, but noted that this was a reoccurring problem in other areas of rheumatology. “The rates are going up in several studies, including in RA, so [in terms of] axial spondyloarthritis and why that happens, we really don’t know.”

When asked about the effect of the loading dose, Dr. Deodhar said that “the load is not really going to take over or have different response by 52 weeks; the load would have a response by 8 weeks or maybe 12 weeks, but then beyond that, I don’t think the load would have any response at all.

“In my clinical experience, speaking outside this trial, load obviously helps the patient quickly to feel better, and so that’s the way I practice my medicine,” he added.

The PREVENT study was sponsored by Novartis, which markets secukinumab. Some of the authors reported relationships with Novartis and many other pharmaceutical companies. Four authors were employees of Novartis.

SOURCE: Deodhar AA et al. Arthritis Rheumatol. 2019;71(suppl 10), Abstract L21.

ATLANTA – Patients with nonradiographic axial spondyloarthritis who received secukinumab with or without loading doses showed improvements in physical function, quality of life, inflammation, and other disease signs and symptoms, according to results from a phase 3 study presented at the annual meeting of the American College of Rheumatology.

Jeff Craven/MDedge News

For patients with nonradiographic axial spondyloarthritis in the double-blind, randomized, placebo-controlled PREVENT trial, these benefits persisted up to 52 weeks, Atul A. Deodhar, MD, professor of medicine in the division of arthritis and rheumatic diseases at Oregon Health & Science University, Portland, said in his presentation.

“This is the largest study done for a biologic agent in nonradiographic axial spondyloarthritis,” Dr. Deodhar said. The trial enrolled 185 patients who received subcutaneous secukinumab (Cosentyx) at a dose of 150 mg, 184 patients who received the medication without a loading dose, and 186 patients who received placebo.

Patients were included if they were aged at least 18 years with 6 months or more of inflammatory back pain, had objective signs of inflammation (sacroiliitis on MRI and/or C-reactive protein [CRP] at 5.0 mg/dL or higher), had active disease and spinal pain according to the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), had total back pain with a visual analog scale of 40 mm or greater, and had not received a tumor necrosis factor inhibitor (TNFi) or had an inadequate response to no more than one TNFi. Patients were also stratified by inflammation measured on MRI and CRP. A little more than half of the patients in each group were women, and at baseline their mean age was 39 years, with a mean symptom duration of more than 8 years and mean Ankylosing Spondylitis Disease Activity Score of 3.5-3.7.

The primary endpoint was at least 40% improvement in Assessment of Spondyloarthritis International Society response criteria (ASAS40) at 16 weeks to meet European Union regulatory requirements and at 52 weeks for the Food and Drug Administration. Escape to open-label secukinumab or standard of care was permitted any time after week 20 for patients deemed to have inadequate response based on clinical judgment of disease activity by the investigator and patient; at 52 weeks, the trial became open label and patients in the placebo group could begin secukinumab or standard of care. The U.S. and European Union analyses were performed independently, with the European analysis including only secukinumab with loading doses and the U.S. analysis including secukinumab without loading.

At 16 weeks, an analysis of the overall population showed that 40.8% of patients in the secukinumab nonloading group had an ASAS40 response, compared with 40.0% in those who got a loading dose and 28.0% with placebo (P less than .05 for both). Among the 90% of patients who were TNFi naive, ASAS40 responses occurred in 42.2% of patients in the nonloading group, 41.5% who received a loading dose, and 29.2% with placebo (P less than .05 for both). ASAS40 response rates persisted at 52 weeks for patients in the nonloading (39.8%), loading (35.4%), and placebo (19.9%) groups (P less than .05).

Over the same time period, the least-square mean changes in total BASDAI score improved from baseline by 2.43 in the nonloading group, 2.35 in the loading group, and 1.46 in the placebo group (P less than .05). The percentage of patients who had 50% or greater improvement in BASDAI was 37% in both treatment groups, compared with 21% with placebo (P less than .05).

Function score as measured by the Bath Ankylosing Spondylitis Functional Index also showed significantly greater improvements at 16 weeks for both loading and nonloading patients versus placebo (–1.75 and ­–1.64 vs. –1.01; P less than .05). Treatment with or without a loading dose led to significant reductions in sacroiliac joint edema on MRI and high-sensitivity CRP. The percentage patients who met ASAS partial remission criteria were significantly higher in the loading (21.6%) and nonloading (21.2%) groups, compared with placebo (7.0%; P less than .05).

Physical function and quality of life assessments at 16 weeks using the 36-item Short Form Health Survey physical component score and the Ankylosing Spondylitis Quality of Life questionnaire showed significant improvements both with and without a loading dose.

There were no new safety concerns with secukinumab that arose in the trial, Dr. Deodhar said.

Dr. Deodhar admitted the placebo effect was high in the PREVENT study, but noted that this was a reoccurring problem in other areas of rheumatology. “The rates are going up in several studies, including in RA, so [in terms of] axial spondyloarthritis and why that happens, we really don’t know.”

When asked about the effect of the loading dose, Dr. Deodhar said that “the load is not really going to take over or have different response by 52 weeks; the load would have a response by 8 weeks or maybe 12 weeks, but then beyond that, I don’t think the load would have any response at all.

“In my clinical experience, speaking outside this trial, load obviously helps the patient quickly to feel better, and so that’s the way I practice my medicine,” he added.

The PREVENT study was sponsored by Novartis, which markets secukinumab. Some of the authors reported relationships with Novartis and many other pharmaceutical companies. Four authors were employees of Novartis.

SOURCE: Deodhar AA et al. Arthritis Rheumatol. 2019;71(suppl 10), Abstract L21.

ATLANTA – Patients with nonradiographic axial spondyloarthritis who received secukinumab with or without loading doses showed improvements in physical function, quality of life, inflammation, and other disease signs and symptoms, according to results from a phase 3 study presented at the annual meeting of the American College of Rheumatology.

Jeff Craven/MDedge News

For patients with nonradiographic axial spondyloarthritis in the double-blind, randomized, placebo-controlled PREVENT trial, these benefits persisted up to 52 weeks, Atul A. Deodhar, MD, professor of medicine in the division of arthritis and rheumatic diseases at Oregon Health & Science University, Portland, said in his presentation.

“This is the largest study done for a biologic agent in nonradiographic axial spondyloarthritis,” Dr. Deodhar said. The trial enrolled 185 patients who received subcutaneous secukinumab (Cosentyx) at a dose of 150 mg, 184 patients who received the medication without a loading dose, and 186 patients who received placebo.

Patients were included if they were aged at least 18 years with 6 months or more of inflammatory back pain, had objective signs of inflammation (sacroiliitis on MRI and/or C-reactive protein [CRP] at 5.0 mg/dL or higher), had active disease and spinal pain according to the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), had total back pain with a visual analog scale of 40 mm or greater, and had not received a tumor necrosis factor inhibitor (TNFi) or had an inadequate response to no more than one TNFi. Patients were also stratified by inflammation measured on MRI and CRP. A little more than half of the patients in each group were women, and at baseline their mean age was 39 years, with a mean symptom duration of more than 8 years and mean Ankylosing Spondylitis Disease Activity Score of 3.5-3.7.

The primary endpoint was at least 40% improvement in Assessment of Spondyloarthritis International Society response criteria (ASAS40) at 16 weeks to meet European Union regulatory requirements and at 52 weeks for the Food and Drug Administration. Escape to open-label secukinumab or standard of care was permitted any time after week 20 for patients deemed to have inadequate response based on clinical judgment of disease activity by the investigator and patient; at 52 weeks, the trial became open label and patients in the placebo group could begin secukinumab or standard of care. The U.S. and European Union analyses were performed independently, with the European analysis including only secukinumab with loading doses and the U.S. analysis including secukinumab without loading.

At 16 weeks, an analysis of the overall population showed that 40.8% of patients in the secukinumab nonloading group had an ASAS40 response, compared with 40.0% in those who got a loading dose and 28.0% with placebo (P less than .05 for both). Among the 90% of patients who were TNFi naive, ASAS40 responses occurred in 42.2% of patients in the nonloading group, 41.5% who received a loading dose, and 29.2% with placebo (P less than .05 for both). ASAS40 response rates persisted at 52 weeks for patients in the nonloading (39.8%), loading (35.4%), and placebo (19.9%) groups (P less than .05).

Over the same time period, the least-square mean changes in total BASDAI score improved from baseline by 2.43 in the nonloading group, 2.35 in the loading group, and 1.46 in the placebo group (P less than .05). The percentage of patients who had 50% or greater improvement in BASDAI was 37% in both treatment groups, compared with 21% with placebo (P less than .05).

Function score as measured by the Bath Ankylosing Spondylitis Functional Index also showed significantly greater improvements at 16 weeks for both loading and nonloading patients versus placebo (–1.75 and ­–1.64 vs. –1.01; P less than .05). Treatment with or without a loading dose led to significant reductions in sacroiliac joint edema on MRI and high-sensitivity CRP. The percentage patients who met ASAS partial remission criteria were significantly higher in the loading (21.6%) and nonloading (21.2%) groups, compared with placebo (7.0%; P less than .05).

Physical function and quality of life assessments at 16 weeks using the 36-item Short Form Health Survey physical component score and the Ankylosing Spondylitis Quality of Life questionnaire showed significant improvements both with and without a loading dose.

There were no new safety concerns with secukinumab that arose in the trial, Dr. Deodhar said.

Dr. Deodhar admitted the placebo effect was high in the PREVENT study, but noted that this was a reoccurring problem in other areas of rheumatology. “The rates are going up in several studies, including in RA, so [in terms of] axial spondyloarthritis and why that happens, we really don’t know.”

When asked about the effect of the loading dose, Dr. Deodhar said that “the load is not really going to take over or have different response by 52 weeks; the load would have a response by 8 weeks or maybe 12 weeks, but then beyond that, I don’t think the load would have any response at all.

“In my clinical experience, speaking outside this trial, load obviously helps the patient quickly to feel better, and so that’s the way I practice my medicine,” he added.

The PREVENT study was sponsored by Novartis, which markets secukinumab. Some of the authors reported relationships with Novartis and many other pharmaceutical companies. Four authors were employees of Novartis.

SOURCE: Deodhar AA et al. Arthritis Rheumatol. 2019;71(suppl 10), Abstract L21.

PHILADELPHIA – Women who underwent either hysterectomy or myomectomy had similar short-term outcomes between 6 weeks and 12 weeks after surgery despite different baseline characteristics, according to recent results from the COMPARE-UF study presented at the annual meeting of the American Society for Reproductive Medicine.

Jeff Craven/MDedge News

“Both hysterectomy and myomectomy can substantially improve women’s quality of life scores and substantially reduce symptom severity,” reported Wanda K. Nicholson, MD, MPH, lead investigator for COMPARE-UF and professor of general obstetrics and gynecology at the University of North Carolina at Chapel Hill.

Researchers included 1,295 women in the COMPARE-UF study who were at least 30 years old, not attempting pregnancy, and undergoing hysterectomy or myomectomy for treatment of fibroids. Overall, 727 patients underwent hysterectomy, and 568 patients underwent myomectomy.

The researchers measured QoL and symptom severity using the Uterine Fibroid Scale-QoL, the EQ-5D, and Visual Analog Scale (VAS). The UFS-QoL contained subscales for concern, activities, energy and mood, control, self-consciousness, and sexual function, while the EQ-5D had subscales for mobility, self-care, usual activities, pain or discomfort, and anxiety or depression.

After surgery, UFS-QoL overall scores were similar in both hysterectomy and myomectomy groups between 6 weeks and 12 weeks (77 vs. 76), but there was less postsurgery symptom severity in the hysterectomy group over the same time period (16 vs. 20; P less than .05). However, both groups had a significant improvement in overall UFS-QoL post surgery (hysterectomy, 31; myomectomy, 30) and in UFS-QoL symptom severity (hysterectomy, 41; myomectomy, 37), Dr. Nicholson noted. EQ-5D VAS scores also were similar in both hysterectomy and myomectomy groups after treatment (82 vs. 79), and showed a 10.9 score improvement in hysterectomy patients and an 8.6 score improvement in myomectomy patients.

“This is really important, because it shows that, regardless of which procedure that you’ve chosen, at least at short-term follow up, it appears that you will have improvement in quality of life,” she said.

When researchers analyzed the UFS-QoL subscale scores, they found patients who underwent abdominal myomectomy scored better than abdominal hysterectomy on the activities subscale (79 vs. 72; P equals .01) and energy/mood subscale (82 vs. 75; P equals .03). In examining minimally invasive procedures, Dr. Nicholson and colleagues found higher improvements in health-related QoL scores among patients undergoing minimally invasive hysterectomy (45-80 vs. 45 vs. 75), and these patients also had lower symptom severity, compared with patients who underwent myomectomy (59-13 vs. 58-21).

“At least at the short-term follow-up, we think that some of that difference that we see in minimally invasive procedures vs. nonminimally invasive may be in part due to women’s perceptions or what their expectations are having minimally invasive surgery, and how they might feel in the short-term follow-up period,” said Dr. Nicholson.

These similar short-term outcomes occurred even though there were significant differences in baseline patient characteristics for the hysterectomy and myomectomy groups, with women undergoing hysterectomy being significantly younger (40 years) than patients undergoing hysterectomy (45 years). Differences also were significant between hysterectomy and myomectomy groups in the percentage of patients who were white (50% vs. 41%; P less than .01), African-American (38% vs. 41%; P less than .01) or other races (12% vs. 18%; P less than .01). There also were significant differences in baseline body mass index between hysterectomy (31 kg/m²) and myomectomy (29 kg/m²) groups.

Patients in both groups further differed in presurgery quality-of-life (QoL) scores.

Women in the hysterectomy group had lower presurgery overall QoL (44 vs. 50), greater symptom severity (60 vs. 52), and lower VAS (69 vs. 73) scores, compared with the myomectomy group (P less than .05). This difference continued in the UFS-QoL subscale scores, where women in the hysterectomy group had significantly lower scores in the concern (38 vs. 45), activities (46 vs. 52), energy/mood (45 vs. 51), control (48 vs. 52), self-consciousness (41 vs. 50), and sexual function (45 vs. 50) subscales, compared with women in the myomectomy group (P less than .05). The researchers used propensity scoring to adjust for baseline characteristics, and inverse propensity weighting to adjust for potential confounding in the multivariate analysis.

COMPARE-UF is funded by the Agency for Healthcare Research and Quality (AHRQ), Patient-Centered Outcomes Research Institute (PCORI), and the National Institutes of Health. Dr. Nicholson reported no relevant conflicts of interest.

SOURCE: Nicholson WK et al. ASRM 2019, Abstract SYT07.

PHILADELPHIA – Women who underwent either hysterectomy or myomectomy had similar short-term outcomes between 6 weeks and 12 weeks after surgery despite different baseline characteristics, according to recent results from the COMPARE-UF study presented at the annual meeting of the American Society for Reproductive Medicine.

Jeff Craven/MDedge News

“Both hysterectomy and myomectomy can substantially improve women’s quality of life scores and substantially reduce symptom severity,” reported Wanda K. Nicholson, MD, MPH, lead investigator for COMPARE-UF and professor of general obstetrics and gynecology at the University of North Carolina at Chapel Hill.

Researchers included 1,295 women in the COMPARE-UF study who were at least 30 years old, not attempting pregnancy, and undergoing hysterectomy or myomectomy for treatment of fibroids. Overall, 727 patients underwent hysterectomy, and 568 patients underwent myomectomy.

The researchers measured QoL and symptom severity using the Uterine Fibroid Scale-QoL, the EQ-5D, and Visual Analog Scale (VAS). The UFS-QoL contained subscales for concern, activities, energy and mood, control, self-consciousness, and sexual function, while the EQ-5D had subscales for mobility, self-care, usual activities, pain or discomfort, and anxiety or depression.

After surgery, UFS-QoL overall scores were similar in both hysterectomy and myomectomy groups between 6 weeks and 12 weeks (77 vs. 76), but there was less postsurgery symptom severity in the hysterectomy group over the same time period (16 vs. 20; P less than .05). However, both groups had a significant improvement in overall UFS-QoL post surgery (hysterectomy, 31; myomectomy, 30) and in UFS-QoL symptom severity (hysterectomy, 41; myomectomy, 37), Dr. Nicholson noted. EQ-5D VAS scores also were similar in both hysterectomy and myomectomy groups after treatment (82 vs. 79), and showed a 10.9 score improvement in hysterectomy patients and an 8.6 score improvement in myomectomy patients.

“This is really important, because it shows that, regardless of which procedure that you’ve chosen, at least at short-term follow up, it appears that you will have improvement in quality of life,” she said.

When researchers analyzed the UFS-QoL subscale scores, they found patients who underwent abdominal myomectomy scored better than abdominal hysterectomy on the activities subscale (79 vs. 72; P equals .01) and energy/mood subscale (82 vs. 75; P equals .03). In examining minimally invasive procedures, Dr. Nicholson and colleagues found higher improvements in health-related QoL scores among patients undergoing minimally invasive hysterectomy (45-80 vs. 45 vs. 75), and these patients also had lower symptom severity, compared with patients who underwent myomectomy (59-13 vs. 58-21).

“At least at the short-term follow-up, we think that some of that difference that we see in minimally invasive procedures vs. nonminimally invasive may be in part due to women’s perceptions or what their expectations are having minimally invasive surgery, and how they might feel in the short-term follow-up period,” said Dr. Nicholson.

These similar short-term outcomes occurred even though there were significant differences in baseline patient characteristics for the hysterectomy and myomectomy groups, with women undergoing hysterectomy being significantly younger (40 years) than patients undergoing hysterectomy (45 years). Differences also were significant between hysterectomy and myomectomy groups in the percentage of patients who were white (50% vs. 41%; P less than .01), African-American (38% vs. 41%; P less than .01) or other races (12% vs. 18%; P less than .01). There also were significant differences in baseline body mass index between hysterectomy (31 kg/m²) and myomectomy (29 kg/m²) groups.

Patients in both groups further differed in presurgery quality-of-life (QoL) scores.

Women in the hysterectomy group had lower presurgery overall QoL (44 vs. 50), greater symptom severity (60 vs. 52), and lower VAS (69 vs. 73) scores, compared with the myomectomy group (P less than .05). This difference continued in the UFS-QoL subscale scores, where women in the hysterectomy group had significantly lower scores in the concern (38 vs. 45), activities (46 vs. 52), energy/mood (45 vs. 51), control (48 vs. 52), self-consciousness (41 vs. 50), and sexual function (45 vs. 50) subscales, compared with women in the myomectomy group (P less than .05). The researchers used propensity scoring to adjust for baseline characteristics, and inverse propensity weighting to adjust for potential confounding in the multivariate analysis.

COMPARE-UF is funded by the Agency for Healthcare Research and Quality (AHRQ), Patient-Centered Outcomes Research Institute (PCORI), and the National Institutes of Health. Dr. Nicholson reported no relevant conflicts of interest.

SOURCE: Nicholson WK et al. ASRM 2019, Abstract SYT07.

PHILADELPHIA – Women who underwent either hysterectomy or myomectomy had similar short-term outcomes between 6 weeks and 12 weeks after surgery despite different baseline characteristics, according to recent results from the COMPARE-UF study presented at the annual meeting of the American Society for Reproductive Medicine.

Jeff Craven/MDedge News

“Both hysterectomy and myomectomy can substantially improve women’s quality of life scores and substantially reduce symptom severity,” reported Wanda K. Nicholson, MD, MPH, lead investigator for COMPARE-UF and professor of general obstetrics and gynecology at the University of North Carolina at Chapel Hill.

Researchers included 1,295 women in the COMPARE-UF study who were at least 30 years old, not attempting pregnancy, and undergoing hysterectomy or myomectomy for treatment of fibroids. Overall, 727 patients underwent hysterectomy, and 568 patients underwent myomectomy.

The researchers measured QoL and symptom severity using the Uterine Fibroid Scale-QoL, the EQ-5D, and Visual Analog Scale (VAS). The UFS-QoL contained subscales for concern, activities, energy and mood, control, self-consciousness, and sexual function, while the EQ-5D had subscales for mobility, self-care, usual activities, pain or discomfort, and anxiety or depression.

After surgery, UFS-QoL overall scores were similar in both hysterectomy and myomectomy groups between 6 weeks and 12 weeks (77 vs. 76), but there was less postsurgery symptom severity in the hysterectomy group over the same time period (16 vs. 20; P less than .05). However, both groups had a significant improvement in overall UFS-QoL post surgery (hysterectomy, 31; myomectomy, 30) and in UFS-QoL symptom severity (hysterectomy, 41; myomectomy, 37), Dr. Nicholson noted. EQ-5D VAS scores also were similar in both hysterectomy and myomectomy groups after treatment (82 vs. 79), and showed a 10.9 score improvement in hysterectomy patients and an 8.6 score improvement in myomectomy patients.

“This is really important, because it shows that, regardless of which procedure that you’ve chosen, at least at short-term follow up, it appears that you will have improvement in quality of life,” she said.

When researchers analyzed the UFS-QoL subscale scores, they found patients who underwent abdominal myomectomy scored better than abdominal hysterectomy on the activities subscale (79 vs. 72; P equals .01) and energy/mood subscale (82 vs. 75; P equals .03). In examining minimally invasive procedures, Dr. Nicholson and colleagues found higher improvements in health-related QoL scores among patients undergoing minimally invasive hysterectomy (45-80 vs. 45 vs. 75), and these patients also had lower symptom severity, compared with patients who underwent myomectomy (59-13 vs. 58-21).

“At least at the short-term follow-up, we think that some of that difference that we see in minimally invasive procedures vs. nonminimally invasive may be in part due to women’s perceptions or what their expectations are having minimally invasive surgery, and how they might feel in the short-term follow-up period,” said Dr. Nicholson.

These similar short-term outcomes occurred even though there were significant differences in baseline patient characteristics for the hysterectomy and myomectomy groups, with women undergoing hysterectomy being significantly younger (40 years) than patients undergoing hysterectomy (45 years). Differences also were significant between hysterectomy and myomectomy groups in the percentage of patients who were white (50% vs. 41%; P less than .01), African-American (38% vs. 41%; P less than .01) or other races (12% vs. 18%; P less than .01). There also were significant differences in baseline body mass index between hysterectomy (31 kg/m²) and myomectomy (29 kg/m²) groups.

Patients in both groups further differed in presurgery quality-of-life (QoL) scores.

Women in the hysterectomy group had lower presurgery overall QoL (44 vs. 50), greater symptom severity (60 vs. 52), and lower VAS (69 vs. 73) scores, compared with the myomectomy group (P less than .05). This difference continued in the UFS-QoL subscale scores, where women in the hysterectomy group had significantly lower scores in the concern (38 vs. 45), activities (46 vs. 52), energy/mood (45 vs. 51), control (48 vs. 52), self-consciousness (41 vs. 50), and sexual function (45 vs. 50) subscales, compared with women in the myomectomy group (P less than .05). The researchers used propensity scoring to adjust for baseline characteristics, and inverse propensity weighting to adjust for potential confounding in the multivariate analysis.

COMPARE-UF is funded by the Agency for Healthcare Research and Quality (AHRQ), Patient-Centered Outcomes Research Institute (PCORI), and the National Institutes of Health. Dr. Nicholson reported no relevant conflicts of interest.

SOURCE: Nicholson WK et al. ASRM 2019, Abstract SYT07.

ATLANTA – Opportunities to escalate or deescalate medications for patients with rheumatoid arthritis via an electronic health record at the point of care led rheumatologists at the Geisinger Medical Center in Danville, Pa., to increase the number of such decisions in their practice.

Jeff Craven/MDedge News

“Opportunities for escalation and de-escalation of therapy are common, even in a well-managed RA population,” Eric D. Newman, MD, director of the department of rheumatology at Geisinger, said in a presentation at the annual meeting of the American College of Rheumatology. “In our hands, over a third of the time, there was an opportunity to change therapy.”

Dr. Newman and colleagues developed a new treat-to-target tab for their (Patient Centric Electronic Redesign) PACER project, an EHR-adjacent system that captures patient and provider data and presents the information in different views, based on desired action items. The target in the study was low disease activity or remission, which was assessed using Clinical Disease Activity Index (CDAI) scores.

The treat-to-target tab offered three options to rheumatologists in real time when meeting with a patient: an escalation opportunity, which was defined as the patient’s two most recent CDAI scores showing moderate to high disease activity; and a deescalation opportunity, defined as a look-back up to 1 year during which at least two CDAI measures were within low to-moderate disease range. There was also a third “leave-alone” option to neither escalate nor deescalate therapy, but the rheumatologist was prompted to explain why if that option is selected, Dr. Newman noted.

In the first phase of releasing the treat-to-target tab, there was low adoption among the 17 rheumatologists at Geisinger: 82% of rheumatologists did not use the tab for escalation therapy, and 64% did not use the tab for deescalation therapy.

That prompted Dr. Newman and colleagues to develop a new version of the treat-to-target tab for phase 2 of the program. “Once they complete their CDAI, if there’s an opportunity, there would be a bright orange button that would glow right in front of them,” Dr. Newman said. “It was really hard to miss, and all they would have to do is click it and it would bring them right to the treat-to-target tab.”

To increase rheumatologists’ use of the new treat-to-target tab, the amount of time spent using the tab and making decisions is presented to them, he said. “It’s actually now part of our quality measure bundle, so every month, they get a leaderboard to see how they compare with their partners,” he noted. “It’s a great way to drive down variability and get everybody approaching the same sort of mean.”

Overall, between July 2018 and May 2019, there were 1,428 treat-to-target opportunities, consisting of 34.2% of RA office visits. Of these, 11.3% were escalation opportunities and 22.9% were deescalation opportunities, Dr. Newman said.

Between phase 1 and phase 2, the rheumatologists’ nonuse of the treat-to-target tab decreased from 82% to 36% for escalation opportunities, and decisions to escalate therapy increased from 10% to 46%. Similarly, nonuse of the treat-to-target tab for deescalation therapy decreased from 64% to 34%, and decisions to deescalate therapy increased from 5% to 17%.

In 49% of escalation opportunities and 80% of deescalation opportunities in phase 2 of the program, rheumatologists made the decision to leave the patient alone. The reasons for not escalating therapy for a patient included an inaccurate CDAI (34%), patient decision (15%), risks outweighing the benefits (15%), and other (37%). “This is interesting, because if you take 49% times 34%, that means that only 17% of the time they felt it didn’t represent what was going on in our department, which is not what we heard from them verbally before this project,” he said. For deescalation opportunities in which the rheumatologist left the patient alone, the most common reasons were hard-to-control disease (46%), patient preference (29%), and poor prognostic factors (25%).

“Keep in mind, some of these patients may have actually already been deescalated prior to this,” Dr. Newman noted. “We’ve actually done some previous work 3 years ago – we provided a visual signal to our physicians that there was a deescalation opportunity, so we may have already accounted for that portion of the population to some extent.”

Dr. Newman said a future goal of the treat-to-target system is to developed more specific treat-to-target strategies to improve the “signal-to-noise” ratio in the system. “Now [that] it’s fully embedded into our routine RA care delivery across our system, our next steps are going to be to use this tool to proactively drive value-concordant decision making and monitor the effect this has on both disease control as well as cost of care,” he said.

Dr. Newman reported no relevant financial disclosures.
 

SOURCE: Newman ED et al. Arthritis Rheumatol. 2019;71(suppl 10). Abstract 1862.

ATLANTA – Opportunities to escalate or deescalate medications for patients with rheumatoid arthritis via an electronic health record at the point of care led rheumatologists at the Geisinger Medical Center in Danville, Pa., to increase the number of such decisions in their practice.

Jeff Craven/MDedge News

“Opportunities for escalation and de-escalation of therapy are common, even in a well-managed RA population,” Eric D. Newman, MD, director of the department of rheumatology at Geisinger, said in a presentation at the annual meeting of the American College of Rheumatology. “In our hands, over a third of the time, there was an opportunity to change therapy.”

Dr. Newman and colleagues developed a new treat-to-target tab for their (Patient Centric Electronic Redesign) PACER project, an EHR-adjacent system that captures patient and provider data and presents the information in different views, based on desired action items. The target in the study was low disease activity or remission, which was assessed using Clinical Disease Activity Index (CDAI) scores.

The treat-to-target tab offered three options to rheumatologists in real time when meeting with a patient: an escalation opportunity, which was defined as the patient’s two most recent CDAI scores showing moderate to high disease activity; and a deescalation opportunity, defined as a look-back up to 1 year during which at least two CDAI measures were within low to-moderate disease range. There was also a third “leave-alone” option to neither escalate nor deescalate therapy, but the rheumatologist was prompted to explain why if that option is selected, Dr. Newman noted.

In the first phase of releasing the treat-to-target tab, there was low adoption among the 17 rheumatologists at Geisinger: 82% of rheumatologists did not use the tab for escalation therapy, and 64% did not use the tab for deescalation therapy.

That prompted Dr. Newman and colleagues to develop a new version of the treat-to-target tab for phase 2 of the program. “Once they complete their CDAI, if there’s an opportunity, there would be a bright orange button that would glow right in front of them,” Dr. Newman said. “It was really hard to miss, and all they would have to do is click it and it would bring them right to the treat-to-target tab.”

To increase rheumatologists’ use of the new treat-to-target tab, the amount of time spent using the tab and making decisions is presented to them, he said. “It’s actually now part of our quality measure bundle, so every month, they get a leaderboard to see how they compare with their partners,” he noted. “It’s a great way to drive down variability and get everybody approaching the same sort of mean.”

Overall, between July 2018 and May 2019, there were 1,428 treat-to-target opportunities, consisting of 34.2% of RA office visits. Of these, 11.3% were escalation opportunities and 22.9% were deescalation opportunities, Dr. Newman said.

Between phase 1 and phase 2, the rheumatologists’ nonuse of the treat-to-target tab decreased from 82% to 36% for escalation opportunities, and decisions to escalate therapy increased from 10% to 46%. Similarly, nonuse of the treat-to-target tab for deescalation therapy decreased from 64% to 34%, and decisions to deescalate therapy increased from 5% to 17%.

In 49% of escalation opportunities and 80% of deescalation opportunities in phase 2 of the program, rheumatologists made the decision to leave the patient alone. The reasons for not escalating therapy for a patient included an inaccurate CDAI (34%), patient decision (15%), risks outweighing the benefits (15%), and other (37%). “This is interesting, because if you take 49% times 34%, that means that only 17% of the time they felt it didn’t represent what was going on in our department, which is not what we heard from them verbally before this project,” he said. For deescalation opportunities in which the rheumatologist left the patient alone, the most common reasons were hard-to-control disease (46%), patient preference (29%), and poor prognostic factors (25%).

“Keep in mind, some of these patients may have actually already been deescalated prior to this,” Dr. Newman noted. “We’ve actually done some previous work 3 years ago – we provided a visual signal to our physicians that there was a deescalation opportunity, so we may have already accounted for that portion of the population to some extent.”

Dr. Newman said a future goal of the treat-to-target system is to developed more specific treat-to-target strategies to improve the “signal-to-noise” ratio in the system. “Now [that] it’s fully embedded into our routine RA care delivery across our system, our next steps are going to be to use this tool to proactively drive value-concordant decision making and monitor the effect this has on both disease control as well as cost of care,” he said.

Dr. Newman reported no relevant financial disclosures.
 

SOURCE: Newman ED et al. Arthritis Rheumatol. 2019;71(suppl 10). Abstract 1862.

ATLANTA – Opportunities to escalate or deescalate medications for patients with rheumatoid arthritis via an electronic health record at the point of care led rheumatologists at the Geisinger Medical Center in Danville, Pa., to increase the number of such decisions in their practice.

Jeff Craven/MDedge News

“Opportunities for escalation and de-escalation of therapy are common, even in a well-managed RA population,” Eric D. Newman, MD, director of the department of rheumatology at Geisinger, said in a presentation at the annual meeting of the American College of Rheumatology. “In our hands, over a third of the time, there was an opportunity to change therapy.”

Dr. Newman and colleagues developed a new treat-to-target tab for their (Patient Centric Electronic Redesign) PACER project, an EHR-adjacent system that captures patient and provider data and presents the information in different views, based on desired action items. The target in the study was low disease activity or remission, which was assessed using Clinical Disease Activity Index (CDAI) scores.

The treat-to-target tab offered three options to rheumatologists in real time when meeting with a patient: an escalation opportunity, which was defined as the patient’s two most recent CDAI scores showing moderate to high disease activity; and a deescalation opportunity, defined as a look-back up to 1 year during which at least two CDAI measures were within low to-moderate disease range. There was also a third “leave-alone” option to neither escalate nor deescalate therapy, but the rheumatologist was prompted to explain why if that option is selected, Dr. Newman noted.

In the first phase of releasing the treat-to-target tab, there was low adoption among the 17 rheumatologists at Geisinger: 82% of rheumatologists did not use the tab for escalation therapy, and 64% did not use the tab for deescalation therapy.

That prompted Dr. Newman and colleagues to develop a new version of the treat-to-target tab for phase 2 of the program. “Once they complete their CDAI, if there’s an opportunity, there would be a bright orange button that would glow right in front of them,” Dr. Newman said. “It was really hard to miss, and all they would have to do is click it and it would bring them right to the treat-to-target tab.”

To increase rheumatologists’ use of the new treat-to-target tab, the amount of time spent using the tab and making decisions is presented to them, he said. “It’s actually now part of our quality measure bundle, so every month, they get a leaderboard to see how they compare with their partners,” he noted. “It’s a great way to drive down variability and get everybody approaching the same sort of mean.”

Overall, between July 2018 and May 2019, there were 1,428 treat-to-target opportunities, consisting of 34.2% of RA office visits. Of these, 11.3% were escalation opportunities and 22.9% were deescalation opportunities, Dr. Newman said.

Between phase 1 and phase 2, the rheumatologists’ nonuse of the treat-to-target tab decreased from 82% to 36% for escalation opportunities, and decisions to escalate therapy increased from 10% to 46%. Similarly, nonuse of the treat-to-target tab for deescalation therapy decreased from 64% to 34%, and decisions to deescalate therapy increased from 5% to 17%.

In 49% of escalation opportunities and 80% of deescalation opportunities in phase 2 of the program, rheumatologists made the decision to leave the patient alone. The reasons for not escalating therapy for a patient included an inaccurate CDAI (34%), patient decision (15%), risks outweighing the benefits (15%), and other (37%). “This is interesting, because if you take 49% times 34%, that means that only 17% of the time they felt it didn’t represent what was going on in our department, which is not what we heard from them verbally before this project,” he said. For deescalation opportunities in which the rheumatologist left the patient alone, the most common reasons were hard-to-control disease (46%), patient preference (29%), and poor prognostic factors (25%).

“Keep in mind, some of these patients may have actually already been deescalated prior to this,” Dr. Newman noted. “We’ve actually done some previous work 3 years ago – we provided a visual signal to our physicians that there was a deescalation opportunity, so we may have already accounted for that portion of the population to some extent.”

Dr. Newman said a future goal of the treat-to-target system is to developed more specific treat-to-target strategies to improve the “signal-to-noise” ratio in the system. “Now [that] it’s fully embedded into our routine RA care delivery across our system, our next steps are going to be to use this tool to proactively drive value-concordant decision making and monitor the effect this has on both disease control as well as cost of care,” he said.

Dr. Newman reported no relevant financial disclosures.
 

SOURCE: Newman ED et al. Arthritis Rheumatol. 2019;71(suppl 10). Abstract 1862.