Ankylosing spondylitis

Long-term tumor necrosis factor inhibitor therapy improved bone mineral density but did not reduce vertebral fractures or radiographic progression in patients with ankylosing spondylitis, according to results from a prospective cohort study.

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The study, published in the Journal of Bone and Mineral Research, not only confirms previous reports showing an improvement of the bone mineral density (BMD) during tumor necrosis factor inhibitor (TNFi) treatment in patients with ankylosing spondylitis but also an increase in the number and severity of vertebral fractures despite TNFi treatment.

K.J. Beek, of the Amsterdam Rheumatology and Immunology Centre in Amsterdam, and colleagues followed 135 patients with ankylosing spondylitis from the Amsterdam Spondyloarthritis cohort who were started on TNFi therapy after treatment failure of a minimum of two NSAIDs. Only study participants who were naive to TNFi therapy were enrolled in the study. The patients had a mean disease duration of nearly 12 years; 70% were men.

After 4 years of anti-TNF therapy, the proportion of patients with a low BMD of the hip on dual-energy x-ray absorptiometry significantly decreased from 40.1% to 31.8% (P = .03) and at the lumbar spine from 40.2% to 25.3% (P less than .001), respectively.

In addition, outcomes related to vertebral fractures, including incidence, prevalence, and severity, did not improve following 4 years of anti-TNF therapy. Vertebral fracture prevalence increased from 11.1% with at least one fracture to 19.3% with at least one fracture at the 4-year follow-up. Most of the vertebral fractures occurred in the thoracic rather than lumbar spine.

Radiographic progression significantly increased over the course of treatment, based on a rise in median modified Stoke Ankylosing Spondylitis Spinal Score from 4.0 at baseline to 6.5 at 4-year follow-up. Patients with vertebral fractures had significantly worse radiographic progression.

“These findings show a contradiction, with improvement of bone mineral density on the one hand but a worsening of the bone processes on the other hand, indicated by the increase of fractures and radiographic progression,” the investigators wrote.

They acknowledged a key limitation of the study was the observational design, which did not include a matched control group.

“A recommendation for future studies would be to replicate our results in larger groups of ankylosing spondylitis patients,” they concluded.

No information on study funding or disclosures was available.

SOURCE: Beek KJ et al. J Bone Miner Res. 2019 Jan 28. doi: 10.1002/jbmr.3684.

Long-term tumor necrosis factor inhibitor therapy improved bone mineral density but did not reduce vertebral fractures or radiographic progression in patients with ankylosing spondylitis, according to results from a prospective cohort study.

©wildpixel/Thinkstock

The study, published in the Journal of Bone and Mineral Research, not only confirms previous reports showing an improvement of the bone mineral density (BMD) during tumor necrosis factor inhibitor (TNFi) treatment in patients with ankylosing spondylitis but also an increase in the number and severity of vertebral fractures despite TNFi treatment.

K.J. Beek, of the Amsterdam Rheumatology and Immunology Centre in Amsterdam, and colleagues followed 135 patients with ankylosing spondylitis from the Amsterdam Spondyloarthritis cohort who were started on TNFi therapy after treatment failure of a minimum of two NSAIDs. Only study participants who were naive to TNFi therapy were enrolled in the study. The patients had a mean disease duration of nearly 12 years; 70% were men.

After 4 years of anti-TNF therapy, the proportion of patients with a low BMD of the hip on dual-energy x-ray absorptiometry significantly decreased from 40.1% to 31.8% (P = .03) and at the lumbar spine from 40.2% to 25.3% (P less than .001), respectively.

In addition, outcomes related to vertebral fractures, including incidence, prevalence, and severity, did not improve following 4 years of anti-TNF therapy. Vertebral fracture prevalence increased from 11.1% with at least one fracture to 19.3% with at least one fracture at the 4-year follow-up. Most of the vertebral fractures occurred in the thoracic rather than lumbar spine.

Radiographic progression significantly increased over the course of treatment, based on a rise in median modified Stoke Ankylosing Spondylitis Spinal Score from 4.0 at baseline to 6.5 at 4-year follow-up. Patients with vertebral fractures had significantly worse radiographic progression.

“These findings show a contradiction, with improvement of bone mineral density on the one hand but a worsening of the bone processes on the other hand, indicated by the increase of fractures and radiographic progression,” the investigators wrote.

They acknowledged a key limitation of the study was the observational design, which did not include a matched control group.

“A recommendation for future studies would be to replicate our results in larger groups of ankylosing spondylitis patients,” they concluded.

No information on study funding or disclosures was available.

SOURCE: Beek KJ et al. J Bone Miner Res. 2019 Jan 28. doi: 10.1002/jbmr.3684.

Long-term tumor necrosis factor inhibitor therapy improved bone mineral density but did not reduce vertebral fractures or radiographic progression in patients with ankylosing spondylitis, according to results from a prospective cohort study.

©wildpixel/Thinkstock

The study, published in the Journal of Bone and Mineral Research, not only confirms previous reports showing an improvement of the bone mineral density (BMD) during tumor necrosis factor inhibitor (TNFi) treatment in patients with ankylosing spondylitis but also an increase in the number and severity of vertebral fractures despite TNFi treatment.

K.J. Beek, of the Amsterdam Rheumatology and Immunology Centre in Amsterdam, and colleagues followed 135 patients with ankylosing spondylitis from the Amsterdam Spondyloarthritis cohort who were started on TNFi therapy after treatment failure of a minimum of two NSAIDs. Only study participants who were naive to TNFi therapy were enrolled in the study. The patients had a mean disease duration of nearly 12 years; 70% were men.

After 4 years of anti-TNF therapy, the proportion of patients with a low BMD of the hip on dual-energy x-ray absorptiometry significantly decreased from 40.1% to 31.8% (P = .03) and at the lumbar spine from 40.2% to 25.3% (P less than .001), respectively.

In addition, outcomes related to vertebral fractures, including incidence, prevalence, and severity, did not improve following 4 years of anti-TNF therapy. Vertebral fracture prevalence increased from 11.1% with at least one fracture to 19.3% with at least one fracture at the 4-year follow-up. Most of the vertebral fractures occurred in the thoracic rather than lumbar spine.

Radiographic progression significantly increased over the course of treatment, based on a rise in median modified Stoke Ankylosing Spondylitis Spinal Score from 4.0 at baseline to 6.5 at 4-year follow-up. Patients with vertebral fractures had significantly worse radiographic progression.

“These findings show a contradiction, with improvement of bone mineral density on the one hand but a worsening of the bone processes on the other hand, indicated by the increase of fractures and radiographic progression,” the investigators wrote.

They acknowledged a key limitation of the study was the observational design, which did not include a matched control group.

“A recommendation for future studies would be to replicate our results in larger groups of ankylosing spondylitis patients,” they concluded.

No information on study funding or disclosures was available.

SOURCE: Beek KJ et al. J Bone Miner Res. 2019 Jan 28. doi: 10.1002/jbmr.3684.

Long-term anti–tumor necrosis factor therapy seemed to slow progression of sacroiliac joint damage in early axial spondyloarthritis in a German study of 42 patients.

They were all part of the ESTHER trial, which found that in early axial spondyloarthritis (axSpA), active inflammatory lesions on MRI improved significantly more with etanercept (Enbrel) than with sulfasalazine-treated patients (Ann Rheum Dis. 2011 Apr 1;70[4]:590-6).

In the new work, published in the Arthritis & Rheumatology, investigators reviewed 42 ESTHER subjects who were on etanercept for up to 6 years and who also had baseline and at least one bilateral sacroiliac joint (SIJ) x-ray at 2-, 4-, or 6-year follow-up. Two blinded readers scored the x-rays, and a sacroiliitis sum score was assigned to each subject. The sum score ranged from 0, meaning no signs of sacroiliitis, to 8, meaning total ankylosis of both SIJs.

The mean progression in sacroiliitis sum score was 0.13 points from baseline to 2 years; followed by a regression of –0.27 points during years 2-4, and –0.09 points from years 4-6. There was no comparator group of untreated patients, but the authors noted that previous work would suggest a slight, but detectable, progression in joint damage over that time.


Elevated C-reactive protein and the presence of osteitis on MRI, meanwhile, were independently associated with progression.

“This is the first study to analyze the long-term (up to 6 years) progression of radiographic sacroiliitis in patients with axSpA treated with an anti-TNF agent, in this case with etanercept. Our results suggest that long-term treatment with a potent anti-inflammatory drug like a TNF inhibitor may influence the evolution of the disease by decelerating the radiographic progression of SIJ [damage] in patients with” early axSpA, wrote the investigators, led by Valeria Rios Rodriguez, MD, of the Charité Universitätsmedizin, Berlin.

Progression from nonradiographic to radiographic axSpA occurred only in the first 2 years of treatment, among 5 of 27 patients, while 2 of 15 patients who started with radiographic disease regressed to nonradiographic axSpA, yielding a net progression of 7.1%.

Although that’s higher than what’s been reported in previous studies, it might be related to greater inflammation in the SIJ at baseline in ESTHER, since active osteitis on MRI was an inclusion criteria. Also, “treatment with a TNF inhibitor ... might have triggered a faster bone repair visible on x-rays as a progression of structural damage,” the investigators said.

The results seem “congruent with the retardation of the spine progression seen in [ankylosing spondylitis] patients treated long-term with TNF inhibitors. ... Long-term treatment with TNF inhibitors could reduce ... new bone formation by preventing the development of new inflammatory lesions resulting in structural damage” of the SIJ, they said, which, in turn, “might have an impact on the functional status and spinal mobility in patients with axSpA, independently of structural damage of the spine.”

Two-thirds of the trial participants were men; the mean age was 34 years, and mean duration of symptoms 3.1 years at baseline. No information was reported on adverse events.

The work was funded by Pfizer, a marketer of etanercept. Some of the investigators disclosed consulting and other payments from the company, as well as other companies involved in marketing and/or development of drugs for axSpA. One investigator was an employee of Pfizer.

[email protected]

SOURCE: Rios Rodriguez V et al. Arthritis Rheumatol. 2019 Jan 9. doi: 10.1002/art.40786

Long-term anti–tumor necrosis factor therapy seemed to slow progression of sacroiliac joint damage in early axial spondyloarthritis in a German study of 42 patients.

They were all part of the ESTHER trial, which found that in early axial spondyloarthritis (axSpA), active inflammatory lesions on MRI improved significantly more with etanercept (Enbrel) than with sulfasalazine-treated patients (Ann Rheum Dis. 2011 Apr 1;70[4]:590-6).

In the new work, published in the Arthritis & Rheumatology, investigators reviewed 42 ESTHER subjects who were on etanercept for up to 6 years and who also had baseline and at least one bilateral sacroiliac joint (SIJ) x-ray at 2-, 4-, or 6-year follow-up. Two blinded readers scored the x-rays, and a sacroiliitis sum score was assigned to each subject. The sum score ranged from 0, meaning no signs of sacroiliitis, to 8, meaning total ankylosis of both SIJs.

The mean progression in sacroiliitis sum score was 0.13 points from baseline to 2 years; followed by a regression of –0.27 points during years 2-4, and –0.09 points from years 4-6. There was no comparator group of untreated patients, but the authors noted that previous work would suggest a slight, but detectable, progression in joint damage over that time.


Elevated C-reactive protein and the presence of osteitis on MRI, meanwhile, were independently associated with progression.

“This is the first study to analyze the long-term (up to 6 years) progression of radiographic sacroiliitis in patients with axSpA treated with an anti-TNF agent, in this case with etanercept. Our results suggest that long-term treatment with a potent anti-inflammatory drug like a TNF inhibitor may influence the evolution of the disease by decelerating the radiographic progression of SIJ [damage] in patients with” early axSpA, wrote the investigators, led by Valeria Rios Rodriguez, MD, of the Charité Universitätsmedizin, Berlin.

Progression from nonradiographic to radiographic axSpA occurred only in the first 2 years of treatment, among 5 of 27 patients, while 2 of 15 patients who started with radiographic disease regressed to nonradiographic axSpA, yielding a net progression of 7.1%.

Although that’s higher than what’s been reported in previous studies, it might be related to greater inflammation in the SIJ at baseline in ESTHER, since active osteitis on MRI was an inclusion criteria. Also, “treatment with a TNF inhibitor ... might have triggered a faster bone repair visible on x-rays as a progression of structural damage,” the investigators said.

The results seem “congruent with the retardation of the spine progression seen in [ankylosing spondylitis] patients treated long-term with TNF inhibitors. ... Long-term treatment with TNF inhibitors could reduce ... new bone formation by preventing the development of new inflammatory lesions resulting in structural damage” of the SIJ, they said, which, in turn, “might have an impact on the functional status and spinal mobility in patients with axSpA, independently of structural damage of the spine.”

Two-thirds of the trial participants were men; the mean age was 34 years, and mean duration of symptoms 3.1 years at baseline. No information was reported on adverse events.

The work was funded by Pfizer, a marketer of etanercept. Some of the investigators disclosed consulting and other payments from the company, as well as other companies involved in marketing and/or development of drugs for axSpA. One investigator was an employee of Pfizer.

[email protected]

SOURCE: Rios Rodriguez V et al. Arthritis Rheumatol. 2019 Jan 9. doi: 10.1002/art.40786

Long-term anti–tumor necrosis factor therapy seemed to slow progression of sacroiliac joint damage in early axial spondyloarthritis in a German study of 42 patients.

They were all part of the ESTHER trial, which found that in early axial spondyloarthritis (axSpA), active inflammatory lesions on MRI improved significantly more with etanercept (Enbrel) than with sulfasalazine-treated patients (Ann Rheum Dis. 2011 Apr 1;70[4]:590-6).

In the new work, published in the Arthritis & Rheumatology, investigators reviewed 42 ESTHER subjects who were on etanercept for up to 6 years and who also had baseline and at least one bilateral sacroiliac joint (SIJ) x-ray at 2-, 4-, or 6-year follow-up. Two blinded readers scored the x-rays, and a sacroiliitis sum score was assigned to each subject. The sum score ranged from 0, meaning no signs of sacroiliitis, to 8, meaning total ankylosis of both SIJs.

The mean progression in sacroiliitis sum score was 0.13 points from baseline to 2 years; followed by a regression of –0.27 points during years 2-4, and –0.09 points from years 4-6. There was no comparator group of untreated patients, but the authors noted that previous work would suggest a slight, but detectable, progression in joint damage over that time.


Elevated C-reactive protein and the presence of osteitis on MRI, meanwhile, were independently associated with progression.

“This is the first study to analyze the long-term (up to 6 years) progression of radiographic sacroiliitis in patients with axSpA treated with an anti-TNF agent, in this case with etanercept. Our results suggest that long-term treatment with a potent anti-inflammatory drug like a TNF inhibitor may influence the evolution of the disease by decelerating the radiographic progression of SIJ [damage] in patients with” early axSpA, wrote the investigators, led by Valeria Rios Rodriguez, MD, of the Charité Universitätsmedizin, Berlin.

Progression from nonradiographic to radiographic axSpA occurred only in the first 2 years of treatment, among 5 of 27 patients, while 2 of 15 patients who started with radiographic disease regressed to nonradiographic axSpA, yielding a net progression of 7.1%.

Although that’s higher than what’s been reported in previous studies, it might be related to greater inflammation in the SIJ at baseline in ESTHER, since active osteitis on MRI was an inclusion criteria. Also, “treatment with a TNF inhibitor ... might have triggered a faster bone repair visible on x-rays as a progression of structural damage,” the investigators said.

The results seem “congruent with the retardation of the spine progression seen in [ankylosing spondylitis] patients treated long-term with TNF inhibitors. ... Long-term treatment with TNF inhibitors could reduce ... new bone formation by preventing the development of new inflammatory lesions resulting in structural damage” of the SIJ, they said, which, in turn, “might have an impact on the functional status and spinal mobility in patients with axSpA, independently of structural damage of the spine.”

Two-thirds of the trial participants were men; the mean age was 34 years, and mean duration of symptoms 3.1 years at baseline. No information was reported on adverse events.

The work was funded by Pfizer, a marketer of etanercept. Some of the investigators disclosed consulting and other payments from the company, as well as other companies involved in marketing and/or development of drugs for axSpA. One investigator was an employee of Pfizer.

[email protected]

SOURCE: Rios Rodriguez V et al. Arthritis Rheumatol. 2019 Jan 9. doi: 10.1002/art.40786

Approximately one in five adults experience persistent back pain that may lead to increased pain, disability, and health care use, according to data from a population-based study of more than 12,000 adults in Canada.

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“Given that back pain [BP] is often recurrent, it is important to understand the course of back pain over time as this can provide additional insights on risk factors for nonfavorable outcomes,” wrote Mayilee Canizares, PhD, and her colleagues at the University Health Network’s Krembil Research Institute in Toronto.

In a longitudinal study published in Arthritis Care & Research, the investigators followed 12,782 adults from 1994 to 2011. The study population was a representative sample of the Canadian population via the National Population Health Survey, which collected data every 2 years for a total of nine cycles of data. They included people aged 15 years or older in 1994-1995 who had at least three cycles of data from baseline onward.

Over the 16-year study period, 46% of the participants reported at least one episode of back pain. Of these, 18% were identified as persistent, 28% as developing, 21% as recovering, and 33% as occasional.

“A major finding from this study is the negative impact of persistent BP on a range of health-related outcomes, including health care use, after adjustments for sociodemographic, behavior-related factors, and comorbidities,” the researchers wrote.

They examined several sociodemographic variables, including age, gender, educational level, and household income, as well as behavior-related variables including physical activity, work activity, smoking status, and obesity. The average age of the participants at baseline was 39 years; 51% were female.


Individuals who reported any back pain were more likely than those with no back pain to be overweight or obese, to smoke, to engage in moderate to heavy physical activity each day, and to have chronic conditions, including arthritis, depression, high blood pressure, and migraine.

Overall, individuals with persistent or developing BP had more pain, disability, health care visits, and medication use, compared with those in the recovery and occasional BP groups. However, individuals in the recovery group showed increased use of opioids and antidepressants over time as well, suggesting a need for long-term monitoring of back pain patients.

The trend in general disability was greatest for individuals in the persistent group followed by the developing group, recovery group, and occasional BP group.

The study findings were limited by several factors, including the use of self-reports, potential selection bias, and the inability to differentiate the specific types of back pain, the researchers noted. However, the results support and extend data from previous studies and provide clinical implications for understanding back pain.

The researchers concluded that “the different trajectory patterns potentially represent subgroups in the population that may require different interventions. In light of the trend of marked worsening outcomes, particularly for the persistent and developing groups, studies are needed to determine the nature of these groups.”

The authors reported no relevant financial conflicts.

SOURCE: Canizares M et al. Arthritis Care Res. 2019 Jan 14. doi: 10.1002/acr.23811.

Approximately one in five adults experience persistent back pain that may lead to increased pain, disability, and health care use, according to data from a population-based study of more than 12,000 adults in Canada.

Thinkstock.com

“Given that back pain [BP] is often recurrent, it is important to understand the course of back pain over time as this can provide additional insights on risk factors for nonfavorable outcomes,” wrote Mayilee Canizares, PhD, and her colleagues at the University Health Network’s Krembil Research Institute in Toronto.

In a longitudinal study published in Arthritis Care & Research, the investigators followed 12,782 adults from 1994 to 2011. The study population was a representative sample of the Canadian population via the National Population Health Survey, which collected data every 2 years for a total of nine cycles of data. They included people aged 15 years or older in 1994-1995 who had at least three cycles of data from baseline onward.

Over the 16-year study period, 46% of the participants reported at least one episode of back pain. Of these, 18% were identified as persistent, 28% as developing, 21% as recovering, and 33% as occasional.

“A major finding from this study is the negative impact of persistent BP on a range of health-related outcomes, including health care use, after adjustments for sociodemographic, behavior-related factors, and comorbidities,” the researchers wrote.

They examined several sociodemographic variables, including age, gender, educational level, and household income, as well as behavior-related variables including physical activity, work activity, smoking status, and obesity. The average age of the participants at baseline was 39 years; 51% were female.


Individuals who reported any back pain were more likely than those with no back pain to be overweight or obese, to smoke, to engage in moderate to heavy physical activity each day, and to have chronic conditions, including arthritis, depression, high blood pressure, and migraine.

Overall, individuals with persistent or developing BP had more pain, disability, health care visits, and medication use, compared with those in the recovery and occasional BP groups. However, individuals in the recovery group showed increased use of opioids and antidepressants over time as well, suggesting a need for long-term monitoring of back pain patients.

The trend in general disability was greatest for individuals in the persistent group followed by the developing group, recovery group, and occasional BP group.

The study findings were limited by several factors, including the use of self-reports, potential selection bias, and the inability to differentiate the specific types of back pain, the researchers noted. However, the results support and extend data from previous studies and provide clinical implications for understanding back pain.

The researchers concluded that “the different trajectory patterns potentially represent subgroups in the population that may require different interventions. In light of the trend of marked worsening outcomes, particularly for the persistent and developing groups, studies are needed to determine the nature of these groups.”

The authors reported no relevant financial conflicts.

SOURCE: Canizares M et al. Arthritis Care Res. 2019 Jan 14. doi: 10.1002/acr.23811.

Approximately one in five adults experience persistent back pain that may lead to increased pain, disability, and health care use, according to data from a population-based study of more than 12,000 adults in Canada.

Thinkstock.com

“Given that back pain [BP] is often recurrent, it is important to understand the course of back pain over time as this can provide additional insights on risk factors for nonfavorable outcomes,” wrote Mayilee Canizares, PhD, and her colleagues at the University Health Network’s Krembil Research Institute in Toronto.

In a longitudinal study published in Arthritis Care & Research, the investigators followed 12,782 adults from 1994 to 2011. The study population was a representative sample of the Canadian population via the National Population Health Survey, which collected data every 2 years for a total of nine cycles of data. They included people aged 15 years or older in 1994-1995 who had at least three cycles of data from baseline onward.

Over the 16-year study period, 46% of the participants reported at least one episode of back pain. Of these, 18% were identified as persistent, 28% as developing, 21% as recovering, and 33% as occasional.

“A major finding from this study is the negative impact of persistent BP on a range of health-related outcomes, including health care use, after adjustments for sociodemographic, behavior-related factors, and comorbidities,” the researchers wrote.

They examined several sociodemographic variables, including age, gender, educational level, and household income, as well as behavior-related variables including physical activity, work activity, smoking status, and obesity. The average age of the participants at baseline was 39 years; 51% were female.


Individuals who reported any back pain were more likely than those with no back pain to be overweight or obese, to smoke, to engage in moderate to heavy physical activity each day, and to have chronic conditions, including arthritis, depression, high blood pressure, and migraine.

Overall, individuals with persistent or developing BP had more pain, disability, health care visits, and medication use, compared with those in the recovery and occasional BP groups. However, individuals in the recovery group showed increased use of opioids and antidepressants over time as well, suggesting a need for long-term monitoring of back pain patients.

The trend in general disability was greatest for individuals in the persistent group followed by the developing group, recovery group, and occasional BP group.

The study findings were limited by several factors, including the use of self-reports, potential selection bias, and the inability to differentiate the specific types of back pain, the researchers noted. However, the results support and extend data from previous studies and provide clinical implications for understanding back pain.

The researchers concluded that “the different trajectory patterns potentially represent subgroups in the population that may require different interventions. In light of the trend of marked worsening outcomes, particularly for the persistent and developing groups, studies are needed to determine the nature of these groups.”

The authors reported no relevant financial conflicts.

SOURCE: Canizares M et al. Arthritis Care Res. 2019 Jan 14. doi: 10.1002/acr.23811.

Patients with ankylosing spondylitis whose baseline C-reactive protein (CRP) levels were more than three times the upper limit of normal were significantly more likely to respond to 12 weeks of etanercept therapy than were patients with normal baseline CRP levels, investigators reported.

In a post hoc study of 867 patients who received etanercept during clinical trials, the adjusted odds of achieving 20% improvement in Assessment of Spondyloarthritis International Society (ASAS20) at week 12 were 190% higher when CRP levels were “very high” rather than normal at baseline (odds ratio, 2.9; 95% confidence interval, 1.8-4.7). Very-high baseline CRP levels (more than three times the upper limit of normal) also significantly predicted week-12 ASAS50, a change in Ankylosing Spondylitis Disease Activity Score based on CRP (ASDAS-CRP) greater than 1.1 (clinically important improvement), and an ASDAS-CRP less than 1.3 (inactive disease), while a normalization of very-high CRP levels by 2, 4, or 8 weeks of treatment was a significant predictor of achieving week-12 ASDAS inactive disease. “Patient-reported outcomes were less consistent predictors of response,” Xenofon Baraliakos, MD, of Ruhr University Bochum in Herne, Germany, and his coinvestigators wrote in Seminars in Arthritis and Rheumatism.


While the advent of tumor necrosis factor (TNF) antagonists has greatly improved outcomes in ankylosing spondylitis, symptom ambiguity and a lack of objective response criteria still impede early diagnosis and radiographic interpretation. Elevated baseline CRP predicted clinical response to anti-TNF therapy by patients with ankylosing spondylitis in several prior post hoc studies. To further evaluate this finding, the researchers pooled and analyzed data from four randomized, placebo-controlled trials of etanercept in adults with ankylosing spondylitis. In all, 43% of patients had a normal baseline CRP level, 34% had a level that was elevated but did not exceed three times the upper limit of normal, and 23% had a very-high level.

Age of onset, disease duration, and baseline Bath Ankylosing Spondylitis Functional Index also predicted response to etanercept therapy. After controlling for these covariates, a very-high baseline CRP remained a significant predictor for all four week-12 outcomes. This finding points to the value of aggressive, early treatment to normalize CRP in patients with ankylosing spondylitis, the researchers wrote. “Bending the curve of inflammation in the early disease may alter the long-term trajectory of ankylosing spondylitis, which is an opportunity that may not exist in the later stages.”

Thus, CRP, in addition to patient-reported and clinical outcomes, might be useful to help monitor response to anti-TNF therapy, the investigators wrote. It remains unclear whether elevated CRP levels also predict future treatment response in patients who are currently clinically improved or stable.

Pfizer funded the post hoc analysis and acquired the company that had funded the trials (Wyeth). Dr. Baraliakos reported consultancy and speaker fees from Pfizer, AbbVie, Bristol-Myers Squibb, Celgene, Chugai, Janssen, Merck, Novartis, Sandoz, and UCB. Two coinvestigators were Pfizer employees. A third coinvestigator was contracted by Pfizer to provide statistical support.

SOURCE: Baraliakos X et al. Semin Arthritis Rheum. 2018 Nov 2. doi: 10.1016/j.semarthrit.2018.10.019.

Patients with ankylosing spondylitis whose baseline C-reactive protein (CRP) levels were more than three times the upper limit of normal were significantly more likely to respond to 12 weeks of etanercept therapy than were patients with normal baseline CRP levels, investigators reported.

In a post hoc study of 867 patients who received etanercept during clinical trials, the adjusted odds of achieving 20% improvement in Assessment of Spondyloarthritis International Society (ASAS20) at week 12 were 190% higher when CRP levels were “very high” rather than normal at baseline (odds ratio, 2.9; 95% confidence interval, 1.8-4.7). Very-high baseline CRP levels (more than three times the upper limit of normal) also significantly predicted week-12 ASAS50, a change in Ankylosing Spondylitis Disease Activity Score based on CRP (ASDAS-CRP) greater than 1.1 (clinically important improvement), and an ASDAS-CRP less than 1.3 (inactive disease), while a normalization of very-high CRP levels by 2, 4, or 8 weeks of treatment was a significant predictor of achieving week-12 ASDAS inactive disease. “Patient-reported outcomes were less consistent predictors of response,” Xenofon Baraliakos, MD, of Ruhr University Bochum in Herne, Germany, and his coinvestigators wrote in Seminars in Arthritis and Rheumatism.


While the advent of tumor necrosis factor (TNF) antagonists has greatly improved outcomes in ankylosing spondylitis, symptom ambiguity and a lack of objective response criteria still impede early diagnosis and radiographic interpretation. Elevated baseline CRP predicted clinical response to anti-TNF therapy by patients with ankylosing spondylitis in several prior post hoc studies. To further evaluate this finding, the researchers pooled and analyzed data from four randomized, placebo-controlled trials of etanercept in adults with ankylosing spondylitis. In all, 43% of patients had a normal baseline CRP level, 34% had a level that was elevated but did not exceed three times the upper limit of normal, and 23% had a very-high level.

Age of onset, disease duration, and baseline Bath Ankylosing Spondylitis Functional Index also predicted response to etanercept therapy. After controlling for these covariates, a very-high baseline CRP remained a significant predictor for all four week-12 outcomes. This finding points to the value of aggressive, early treatment to normalize CRP in patients with ankylosing spondylitis, the researchers wrote. “Bending the curve of inflammation in the early disease may alter the long-term trajectory of ankylosing spondylitis, which is an opportunity that may not exist in the later stages.”

Thus, CRP, in addition to patient-reported and clinical outcomes, might be useful to help monitor response to anti-TNF therapy, the investigators wrote. It remains unclear whether elevated CRP levels also predict future treatment response in patients who are currently clinically improved or stable.

Pfizer funded the post hoc analysis and acquired the company that had funded the trials (Wyeth). Dr. Baraliakos reported consultancy and speaker fees from Pfizer, AbbVie, Bristol-Myers Squibb, Celgene, Chugai, Janssen, Merck, Novartis, Sandoz, and UCB. Two coinvestigators were Pfizer employees. A third coinvestigator was contracted by Pfizer to provide statistical support.

SOURCE: Baraliakos X et al. Semin Arthritis Rheum. 2018 Nov 2. doi: 10.1016/j.semarthrit.2018.10.019.

Patients with ankylosing spondylitis whose baseline C-reactive protein (CRP) levels were more than three times the upper limit of normal were significantly more likely to respond to 12 weeks of etanercept therapy than were patients with normal baseline CRP levels, investigators reported.

In a post hoc study of 867 patients who received etanercept during clinical trials, the adjusted odds of achieving 20% improvement in Assessment of Spondyloarthritis International Society (ASAS20) at week 12 were 190% higher when CRP levels were “very high” rather than normal at baseline (odds ratio, 2.9; 95% confidence interval, 1.8-4.7). Very-high baseline CRP levels (more than three times the upper limit of normal) also significantly predicted week-12 ASAS50, a change in Ankylosing Spondylitis Disease Activity Score based on CRP (ASDAS-CRP) greater than 1.1 (clinically important improvement), and an ASDAS-CRP less than 1.3 (inactive disease), while a normalization of very-high CRP levels by 2, 4, or 8 weeks of treatment was a significant predictor of achieving week-12 ASDAS inactive disease. “Patient-reported outcomes were less consistent predictors of response,” Xenofon Baraliakos, MD, of Ruhr University Bochum in Herne, Germany, and his coinvestigators wrote in Seminars in Arthritis and Rheumatism.


While the advent of tumor necrosis factor (TNF) antagonists has greatly improved outcomes in ankylosing spondylitis, symptom ambiguity and a lack of objective response criteria still impede early diagnosis and radiographic interpretation. Elevated baseline CRP predicted clinical response to anti-TNF therapy by patients with ankylosing spondylitis in several prior post hoc studies. To further evaluate this finding, the researchers pooled and analyzed data from four randomized, placebo-controlled trials of etanercept in adults with ankylosing spondylitis. In all, 43% of patients had a normal baseline CRP level, 34% had a level that was elevated but did not exceed three times the upper limit of normal, and 23% had a very-high level.

Age of onset, disease duration, and baseline Bath Ankylosing Spondylitis Functional Index also predicted response to etanercept therapy. After controlling for these covariates, a very-high baseline CRP remained a significant predictor for all four week-12 outcomes. This finding points to the value of aggressive, early treatment to normalize CRP in patients with ankylosing spondylitis, the researchers wrote. “Bending the curve of inflammation in the early disease may alter the long-term trajectory of ankylosing spondylitis, which is an opportunity that may not exist in the later stages.”

Thus, CRP, in addition to patient-reported and clinical outcomes, might be useful to help monitor response to anti-TNF therapy, the investigators wrote. It remains unclear whether elevated CRP levels also predict future treatment response in patients who are currently clinically improved or stable.

Pfizer funded the post hoc analysis and acquired the company that had funded the trials (Wyeth). Dr. Baraliakos reported consultancy and speaker fees from Pfizer, AbbVie, Bristol-Myers Squibb, Celgene, Chugai, Janssen, Merck, Novartis, Sandoz, and UCB. Two coinvestigators were Pfizer employees. A third coinvestigator was contracted by Pfizer to provide statistical support.

SOURCE: Baraliakos X et al. Semin Arthritis Rheum. 2018 Nov 2. doi: 10.1016/j.semarthrit.2018.10.019.

A back pain screening questionnaire developed for ankylosing spondylitis performs well for identifying the subset of axial psoriatic arthritis patients who have active symptoms, according to researchers.

The inflammatory back pain criteria didn’t perform as well when patients with established disease but no symptoms were included, though using a lower cutoff point for the questionnaire improved its sensitivity, the researchers reported in the Annals of the Rheumatic Diseases.

Previous investigations showed that the inflammatory back pain criteria, as defined by the Assessment of Spondyloarthritis International Society (ASAS), had low sensitivity and high specificity for axial involvement in psoriatic arthritis.

Those earlier studies may have registered suboptimal performance of the inflammatory back pain criteria by not distinguishing between patients with axial disease in remission and those with active symptoms, according to Muhammad Haroon, PhD, of the division of rheumatology at University Hospital Kerry in Tralee, Ireland, and his coinvestigators.

The present study, which they said represents a much larger cohort than earlier investigations, included 406 patients with psoriatic arthritis, about one-quarter of whom had rheumatologist-diagnosed axial psoriatic arthritis. The mean age of the axial psoriatic arthritis patients was 51 years and 53% were male.

The researchers found that the inflammatory back pain criteria had poor sensitivity but good specificity at 59% and 84%, respectively, in patients with established axial psoriatic arthritis, defined as axial disease regardless of whether it was active or in remission.

By contrast, the criteria had good sensitivity and good specificity at 82% and 88%, respectively, in patients who had active axial psoriatic arthritis, according to the investigators.

The standard cutoff points used by the ASAS inflammatory back pain criteria may be too high for screening for early disease or for evaluating patients already receiving systemic therapies for psoriatic disease, the investigators said.

Looking at a lower cutoff point of three of five ASAS criteria, sensitivity was “quite high” for detecting established axial psoriatic arthritis, they said, increasing from 59% to 84%, while specificity remained relatively high, decreasing from 84% to 80%.

“We suggest that the standard cutoffs for this questionnaire be used for patients with active axial psoriatic arthritis, and the lower cutoffs should be used among patients with established axial psoriatic arthritis, where patients can potentially be in remission or partial remission,” they wrote in their report.

These findings could have important implications for the use of this screening tool in patients with psoriatic arthritis; however, more research is needed to validate the observations, the researchers cautioned.

Dr. Haroon reported competing interests related to AbbVie, Pfizer, and Celgene.

SOURCE: Haroon M et al. Ann Rheum Dis. 2018 Dec 14. doi: 10.1136/annrheumdis-2018-214583.

A back pain screening questionnaire developed for ankylosing spondylitis performs well for identifying the subset of axial psoriatic arthritis patients who have active symptoms, according to researchers.

The inflammatory back pain criteria didn’t perform as well when patients with established disease but no symptoms were included, though using a lower cutoff point for the questionnaire improved its sensitivity, the researchers reported in the Annals of the Rheumatic Diseases.

Previous investigations showed that the inflammatory back pain criteria, as defined by the Assessment of Spondyloarthritis International Society (ASAS), had low sensitivity and high specificity for axial involvement in psoriatic arthritis.

Those earlier studies may have registered suboptimal performance of the inflammatory back pain criteria by not distinguishing between patients with axial disease in remission and those with active symptoms, according to Muhammad Haroon, PhD, of the division of rheumatology at University Hospital Kerry in Tralee, Ireland, and his coinvestigators.

The present study, which they said represents a much larger cohort than earlier investigations, included 406 patients with psoriatic arthritis, about one-quarter of whom had rheumatologist-diagnosed axial psoriatic arthritis. The mean age of the axial psoriatic arthritis patients was 51 years and 53% were male.

The researchers found that the inflammatory back pain criteria had poor sensitivity but good specificity at 59% and 84%, respectively, in patients with established axial psoriatic arthritis, defined as axial disease regardless of whether it was active or in remission.

By contrast, the criteria had good sensitivity and good specificity at 82% and 88%, respectively, in patients who had active axial psoriatic arthritis, according to the investigators.

The standard cutoff points used by the ASAS inflammatory back pain criteria may be too high for screening for early disease or for evaluating patients already receiving systemic therapies for psoriatic disease, the investigators said.

Looking at a lower cutoff point of three of five ASAS criteria, sensitivity was “quite high” for detecting established axial psoriatic arthritis, they said, increasing from 59% to 84%, while specificity remained relatively high, decreasing from 84% to 80%.

“We suggest that the standard cutoffs for this questionnaire be used for patients with active axial psoriatic arthritis, and the lower cutoffs should be used among patients with established axial psoriatic arthritis, where patients can potentially be in remission or partial remission,” they wrote in their report.

These findings could have important implications for the use of this screening tool in patients with psoriatic arthritis; however, more research is needed to validate the observations, the researchers cautioned.

Dr. Haroon reported competing interests related to AbbVie, Pfizer, and Celgene.

SOURCE: Haroon M et al. Ann Rheum Dis. 2018 Dec 14. doi: 10.1136/annrheumdis-2018-214583.

A back pain screening questionnaire developed for ankylosing spondylitis performs well for identifying the subset of axial psoriatic arthritis patients who have active symptoms, according to researchers.

The inflammatory back pain criteria didn’t perform as well when patients with established disease but no symptoms were included, though using a lower cutoff point for the questionnaire improved its sensitivity, the researchers reported in the Annals of the Rheumatic Diseases.

Previous investigations showed that the inflammatory back pain criteria, as defined by the Assessment of Spondyloarthritis International Society (ASAS), had low sensitivity and high specificity for axial involvement in psoriatic arthritis.

Those earlier studies may have registered suboptimal performance of the inflammatory back pain criteria by not distinguishing between patients with axial disease in remission and those with active symptoms, according to Muhammad Haroon, PhD, of the division of rheumatology at University Hospital Kerry in Tralee, Ireland, and his coinvestigators.

The present study, which they said represents a much larger cohort than earlier investigations, included 406 patients with psoriatic arthritis, about one-quarter of whom had rheumatologist-diagnosed axial psoriatic arthritis. The mean age of the axial psoriatic arthritis patients was 51 years and 53% were male.

The researchers found that the inflammatory back pain criteria had poor sensitivity but good specificity at 59% and 84%, respectively, in patients with established axial psoriatic arthritis, defined as axial disease regardless of whether it was active or in remission.

By contrast, the criteria had good sensitivity and good specificity at 82% and 88%, respectively, in patients who had active axial psoriatic arthritis, according to the investigators.

The standard cutoff points used by the ASAS inflammatory back pain criteria may be too high for screening for early disease or for evaluating patients already receiving systemic therapies for psoriatic disease, the investigators said.

Looking at a lower cutoff point of three of five ASAS criteria, sensitivity was “quite high” for detecting established axial psoriatic arthritis, they said, increasing from 59% to 84%, while specificity remained relatively high, decreasing from 84% to 80%.

“We suggest that the standard cutoffs for this questionnaire be used for patients with active axial psoriatic arthritis, and the lower cutoffs should be used among patients with established axial psoriatic arthritis, where patients can potentially be in remission or partial remission,” they wrote in their report.

These findings could have important implications for the use of this screening tool in patients with psoriatic arthritis; however, more research is needed to validate the observations, the researchers cautioned.

Dr. Haroon reported competing interests related to AbbVie, Pfizer, and Celgene.

SOURCE: Haroon M et al. Ann Rheum Dis. 2018 Dec 14. doi: 10.1136/annrheumdis-2018-214583.

Patients with tumor necrosis factor inhibitor–induced psoriasis could potentially be switched to a different drug class if they have moderate to severe skin eruption or mild skin eruption with an uncontrolled underlying disease such as inflammatory bowel disease, psoriasis, psoriatic arthritis, or rheumatoid arthritis, according to a new treatment algorithm proposed by researchers from Brigham and Women’s Hospital and Harvard Medical School in Boston.

The researchers outlined the prevalence of tumor necrosis factor–alpha inhibitor (TNFi)-induced psoriasis in a literature review of inflammatory bowel disease (IBD), psoriasis, psoriatic arthritis (PsA), and rheumatoid arthritis (RA) and identified an estimated rate of between 2.3% and 5% in patients with RA and between 1.6% and 2.7% in patients with IBD. Although there have been reports of TNFi-induced psoriasis in patients with psoriasis and PsA, the prevalence is unclear, they wrote in the Journal of Psoriasis and Psoriatic Arthritis.

The authors then created an algorithm to manage and treat TNFi-induced psoriasiform skin eruptions with decisions to continue therapy and “treat through” symptoms, switch to a different anti-TNF therapy, or switch to a different drug class based on severity of symptoms, whether the underlying disease is well controlled, and how patients with those underlying diseases have fared with those specific therapies or agents.

“We’ve shifted gears over the past decade, and we’ve gone from having very few agents and trying to keep patients desperately on one or two agents because we didn’t want to have to give up on them for their other comorbid disease, whether it was Crohn’s, colitis, RA, or whatever it may be,” senior author Joseph Merola, MD, director of the Center for Skin and Related Musculoskeletal Diseases at Brigham and Women’s Hospital, Boston, said in an interview. “We’re now in an area where we can have an algorithm like this, and we have so many more mechanistic options to move to.”

Dr. Merola, who is board certified in dermatology and rheumatology, said the algorithm is meant to “open a dialogue” with other specialists in different areas and raise awareness of treatments in related but separate fields. For diseases not often seen by more than one specialty, with the exception of psoriasis and PsA, he said that “the idea is to start a dialogue and increase communication between specialists.”

Dr. Merola noted that while the algorithm in many respects is meant to guide a physician in a specialty in appropriate medication decisions, at the same time he hopes that “it opens a dialogue and communication with the other specialty who tends to oversee this particular disease state or class of medicine to really work together to try to find the right drug for the right person.”

For patients with a mild skin eruption and a controlled underlying disease, the algorithm recommends a “treat through” approach by continuing anti-TNF therapy and treating psoriasis symptoms with topical steroids, ultraviolet therapy, methotrexate, cyclosporine, or acitretin, and to consider dapsone in cases of pustular psoriasis. However, the researchers noted that “treat through” studies have reported complete symptom resolution in 26%-41% of patients.

For patients with recalcitrant or worsening TNFi-induced psoriasis or patients with mild skin eruptions with an uncontrolled underlying disease, the researchers proposed considering switching to a different anti-TNF therapy, although studies have shown complete resolution of symptoms in only 5%-37% of patients.

If patients worsen from there, or if they have moderate to-severe skin eruption with uncontrolled underlying disease, they could be considered for switching to a different drug class and treated based on their underlying disease, along with treatment for psoriasis symptoms. This approach has been shown to completely resolve lesions in up to 64% of cases, they said. IBD patients could benefit from ustekinumab, vedolizumab, 6-mercaptopurine, or azathioprine as an alternative to anti-TNF therapy. Those patients with psoriasis should be considered for guselkumab, while ustekinumab, ixekizumab, secukinumab, and apremilast are effective treatments for patients with psoriasis and PsA. Patients with RA could receive treatment with tocilizumab, rituximab, abatacept, and tofacitinib, the authors wrote.

Dr. Merola reported serving as a consultant and/or investigator for Merck Research Laboratories, AbbVie, Dermavant, Eli Lilly, Novartis, Janssen, UCB, Samumed, Celgene, Sanofi Regeneron, GlaxoSmithKline, Almirall, Sun Pharma, Biogen, Pfizer, Incyte, Aclaris, and Leo Pharma.

SOURCE: Li SJ et al. J Psoriasis Psoriatic Arthritis. 2018 Nov 21. doi: 10.1177/2475530318810851.

Patients with tumor necrosis factor inhibitor–induced psoriasis could potentially be switched to a different drug class if they have moderate to severe skin eruption or mild skin eruption with an uncontrolled underlying disease such as inflammatory bowel disease, psoriasis, psoriatic arthritis, or rheumatoid arthritis, according to a new treatment algorithm proposed by researchers from Brigham and Women’s Hospital and Harvard Medical School in Boston.

The researchers outlined the prevalence of tumor necrosis factor–alpha inhibitor (TNFi)-induced psoriasis in a literature review of inflammatory bowel disease (IBD), psoriasis, psoriatic arthritis (PsA), and rheumatoid arthritis (RA) and identified an estimated rate of between 2.3% and 5% in patients with RA and between 1.6% and 2.7% in patients with IBD. Although there have been reports of TNFi-induced psoriasis in patients with psoriasis and PsA, the prevalence is unclear, they wrote in the Journal of Psoriasis and Psoriatic Arthritis.

The authors then created an algorithm to manage and treat TNFi-induced psoriasiform skin eruptions with decisions to continue therapy and “treat through” symptoms, switch to a different anti-TNF therapy, or switch to a different drug class based on severity of symptoms, whether the underlying disease is well controlled, and how patients with those underlying diseases have fared with those specific therapies or agents.

“We’ve shifted gears over the past decade, and we’ve gone from having very few agents and trying to keep patients desperately on one or two agents because we didn’t want to have to give up on them for their other comorbid disease, whether it was Crohn’s, colitis, RA, or whatever it may be,” senior author Joseph Merola, MD, director of the Center for Skin and Related Musculoskeletal Diseases at Brigham and Women’s Hospital, Boston, said in an interview. “We’re now in an area where we can have an algorithm like this, and we have so many more mechanistic options to move to.”

Dr. Merola, who is board certified in dermatology and rheumatology, said the algorithm is meant to “open a dialogue” with other specialists in different areas and raise awareness of treatments in related but separate fields. For diseases not often seen by more than one specialty, with the exception of psoriasis and PsA, he said that “the idea is to start a dialogue and increase communication between specialists.”

Dr. Merola noted that while the algorithm in many respects is meant to guide a physician in a specialty in appropriate medication decisions, at the same time he hopes that “it opens a dialogue and communication with the other specialty who tends to oversee this particular disease state or class of medicine to really work together to try to find the right drug for the right person.”

For patients with a mild skin eruption and a controlled underlying disease, the algorithm recommends a “treat through” approach by continuing anti-TNF therapy and treating psoriasis symptoms with topical steroids, ultraviolet therapy, methotrexate, cyclosporine, or acitretin, and to consider dapsone in cases of pustular psoriasis. However, the researchers noted that “treat through” studies have reported complete symptom resolution in 26%-41% of patients.

For patients with recalcitrant or worsening TNFi-induced psoriasis or patients with mild skin eruptions with an uncontrolled underlying disease, the researchers proposed considering switching to a different anti-TNF therapy, although studies have shown complete resolution of symptoms in only 5%-37% of patients.

If patients worsen from there, or if they have moderate to-severe skin eruption with uncontrolled underlying disease, they could be considered for switching to a different drug class and treated based on their underlying disease, along with treatment for psoriasis symptoms. This approach has been shown to completely resolve lesions in up to 64% of cases, they said. IBD patients could benefit from ustekinumab, vedolizumab, 6-mercaptopurine, or azathioprine as an alternative to anti-TNF therapy. Those patients with psoriasis should be considered for guselkumab, while ustekinumab, ixekizumab, secukinumab, and apremilast are effective treatments for patients with psoriasis and PsA. Patients with RA could receive treatment with tocilizumab, rituximab, abatacept, and tofacitinib, the authors wrote.

Dr. Merola reported serving as a consultant and/or investigator for Merck Research Laboratories, AbbVie, Dermavant, Eli Lilly, Novartis, Janssen, UCB, Samumed, Celgene, Sanofi Regeneron, GlaxoSmithKline, Almirall, Sun Pharma, Biogen, Pfizer, Incyte, Aclaris, and Leo Pharma.

SOURCE: Li SJ et al. J Psoriasis Psoriatic Arthritis. 2018 Nov 21. doi: 10.1177/2475530318810851.

Patients with tumor necrosis factor inhibitor–induced psoriasis could potentially be switched to a different drug class if they have moderate to severe skin eruption or mild skin eruption with an uncontrolled underlying disease such as inflammatory bowel disease, psoriasis, psoriatic arthritis, or rheumatoid arthritis, according to a new treatment algorithm proposed by researchers from Brigham and Women’s Hospital and Harvard Medical School in Boston.

The researchers outlined the prevalence of tumor necrosis factor–alpha inhibitor (TNFi)-induced psoriasis in a literature review of inflammatory bowel disease (IBD), psoriasis, psoriatic arthritis (PsA), and rheumatoid arthritis (RA) and identified an estimated rate of between 2.3% and 5% in patients with RA and between 1.6% and 2.7% in patients with IBD. Although there have been reports of TNFi-induced psoriasis in patients with psoriasis and PsA, the prevalence is unclear, they wrote in the Journal of Psoriasis and Psoriatic Arthritis.

The authors then created an algorithm to manage and treat TNFi-induced psoriasiform skin eruptions with decisions to continue therapy and “treat through” symptoms, switch to a different anti-TNF therapy, or switch to a different drug class based on severity of symptoms, whether the underlying disease is well controlled, and how patients with those underlying diseases have fared with those specific therapies or agents.

“We’ve shifted gears over the past decade, and we’ve gone from having very few agents and trying to keep patients desperately on one or two agents because we didn’t want to have to give up on them for their other comorbid disease, whether it was Crohn’s, colitis, RA, or whatever it may be,” senior author Joseph Merola, MD, director of the Center for Skin and Related Musculoskeletal Diseases at Brigham and Women’s Hospital, Boston, said in an interview. “We’re now in an area where we can have an algorithm like this, and we have so many more mechanistic options to move to.”

Dr. Merola, who is board certified in dermatology and rheumatology, said the algorithm is meant to “open a dialogue” with other specialists in different areas and raise awareness of treatments in related but separate fields. For diseases not often seen by more than one specialty, with the exception of psoriasis and PsA, he said that “the idea is to start a dialogue and increase communication between specialists.”

Dr. Merola noted that while the algorithm in many respects is meant to guide a physician in a specialty in appropriate medication decisions, at the same time he hopes that “it opens a dialogue and communication with the other specialty who tends to oversee this particular disease state or class of medicine to really work together to try to find the right drug for the right person.”

For patients with a mild skin eruption and a controlled underlying disease, the algorithm recommends a “treat through” approach by continuing anti-TNF therapy and treating psoriasis symptoms with topical steroids, ultraviolet therapy, methotrexate, cyclosporine, or acitretin, and to consider dapsone in cases of pustular psoriasis. However, the researchers noted that “treat through” studies have reported complete symptom resolution in 26%-41% of patients.

For patients with recalcitrant or worsening TNFi-induced psoriasis or patients with mild skin eruptions with an uncontrolled underlying disease, the researchers proposed considering switching to a different anti-TNF therapy, although studies have shown complete resolution of symptoms in only 5%-37% of patients.

If patients worsen from there, or if they have moderate to-severe skin eruption with uncontrolled underlying disease, they could be considered for switching to a different drug class and treated based on their underlying disease, along with treatment for psoriasis symptoms. This approach has been shown to completely resolve lesions in up to 64% of cases, they said. IBD patients could benefit from ustekinumab, vedolizumab, 6-mercaptopurine, or azathioprine as an alternative to anti-TNF therapy. Those patients with psoriasis should be considered for guselkumab, while ustekinumab, ixekizumab, secukinumab, and apremilast are effective treatments for patients with psoriasis and PsA. Patients with RA could receive treatment with tocilizumab, rituximab, abatacept, and tofacitinib, the authors wrote.

Dr. Merola reported serving as a consultant and/or investigator for Merck Research Laboratories, AbbVie, Dermavant, Eli Lilly, Novartis, Janssen, UCB, Samumed, Celgene, Sanofi Regeneron, GlaxoSmithKline, Almirall, Sun Pharma, Biogen, Pfizer, Incyte, Aclaris, and Leo Pharma.

SOURCE: Li SJ et al. J Psoriasis Psoriatic Arthritis. 2018 Nov 21. doi: 10.1177/2475530318810851.

The Food and Drug Administration has approved the adalimumab biosimilar Hyrimoz (adalimumab-adaz) for a variety of conditions, according to Sandoz, the drug’s manufacturer and a division of Novartis.

Wikimedia Commons/FitzColinGerald/Creative Commons License

FDA approval for Hyrimoz is based on a randomized, double-blind, three-arm, parallel biosimilarity study that demonstrated equivalence for all primary pharmacokinetic parameters, according to the press release. A second study confirmed these results in patients with moderate to severe plaque psoriasis, with Hyrimoz having a safety profile similar to that of adalimumab. Hyrimoz was approved in Europe in July 2018.

Hyrimoz has been approved to treat rheumatoid arthritis, juvenile idiopathic arthritis in patients aged 4 years and older, psoriatic arthritis, ankylosing spondylitis, adult Crohn’s disease, ulcerative colitis, and plaque psoriasis. The most common adverse events associated with the drug, according to the label, are infections, injection site reactions, headache, and rash.

Hyrimoz is the third adalimumab biosimilar approved by the FDA.

“Biosimilars can help people suffering from chronic, debilitating conditions gain expanded access to important medicines that may change the outcome of their disease. With the FDA approval of Hyrimoz, Sandoz is one step closer to offering U.S. patients with autoimmune diseases the same critical access already available in Europe,” Stefan Hendriks, global head of biopharmaceuticals at Sandoz, said in the press release.

Find the full press release on the Novartis website.

[email protected]

The Food and Drug Administration has approved the adalimumab biosimilar Hyrimoz (adalimumab-adaz) for a variety of conditions, according to Sandoz, the drug’s manufacturer and a division of Novartis.

Wikimedia Commons/FitzColinGerald/Creative Commons License

FDA approval for Hyrimoz is based on a randomized, double-blind, three-arm, parallel biosimilarity study that demonstrated equivalence for all primary pharmacokinetic parameters, according to the press release. A second study confirmed these results in patients with moderate to severe plaque psoriasis, with Hyrimoz having a safety profile similar to that of adalimumab. Hyrimoz was approved in Europe in July 2018.

Hyrimoz has been approved to treat rheumatoid arthritis, juvenile idiopathic arthritis in patients aged 4 years and older, psoriatic arthritis, ankylosing spondylitis, adult Crohn’s disease, ulcerative colitis, and plaque psoriasis. The most common adverse events associated with the drug, according to the label, are infections, injection site reactions, headache, and rash.

Hyrimoz is the third adalimumab biosimilar approved by the FDA.

“Biosimilars can help people suffering from chronic, debilitating conditions gain expanded access to important medicines that may change the outcome of their disease. With the FDA approval of Hyrimoz, Sandoz is one step closer to offering U.S. patients with autoimmune diseases the same critical access already available in Europe,” Stefan Hendriks, global head of biopharmaceuticals at Sandoz, said in the press release.

Find the full press release on the Novartis website.

[email protected]

The Food and Drug Administration has approved the adalimumab biosimilar Hyrimoz (adalimumab-adaz) for a variety of conditions, according to Sandoz, the drug’s manufacturer and a division of Novartis.

Wikimedia Commons/FitzColinGerald/Creative Commons License

FDA approval for Hyrimoz is based on a randomized, double-blind, three-arm, parallel biosimilarity study that demonstrated equivalence for all primary pharmacokinetic parameters, according to the press release. A second study confirmed these results in patients with moderate to severe plaque psoriasis, with Hyrimoz having a safety profile similar to that of adalimumab. Hyrimoz was approved in Europe in July 2018.

Hyrimoz has been approved to treat rheumatoid arthritis, juvenile idiopathic arthritis in patients aged 4 years and older, psoriatic arthritis, ankylosing spondylitis, adult Crohn’s disease, ulcerative colitis, and plaque psoriasis. The most common adverse events associated with the drug, according to the label, are infections, injection site reactions, headache, and rash.

Hyrimoz is the third adalimumab biosimilar approved by the FDA.

“Biosimilars can help people suffering from chronic, debilitating conditions gain expanded access to important medicines that may change the outcome of their disease. With the FDA approval of Hyrimoz, Sandoz is one step closer to offering U.S. patients with autoimmune diseases the same critical access already available in Europe,” Stefan Hendriks, global head of biopharmaceuticals at Sandoz, said in the press release.

Find the full press release on the Novartis website.

[email protected]

CHICAGO – Help is on the way for rheumatologists who may feel out of their depth regarding reproductive health issues in their patients.

Bruce Jancin/MDedge News

“Our patients, fortunately, are pursuing pregnancy more often now than in years past. One of the key messages of the guidelines is that patients really do want to discuss these topics with their rheumatologist, even though that often does not happen now. What patients told us [in the guideline-development process] is their rheumatologist knows them better than their gynecologist or any of their other doctors because we have followed them for a long period of time and we understand their disease and their symptoms. They really want our input on questions about contraception, when to plan a pregnancy, and medication use,” said Dr. Sammaritano of the Hospital for Special Surgery and Cornell University in New York.

The guidelines were created over the course of a year and a half with extensive input from ob.gyns., as well as a patient panel. The project included a systematic review of more than 300 published studies in which guideline panelists attempt to find answers to an initial list of 370 questions. Dr. Sammaritano predicted that the guidelines will prove to be useful not only for rheumatologists, but for their colleagues in ob.gyn. as well. Just as rheumatologists likely haven’t kept up with the sea changes that have occurred in ob.gyn. since their medical school days, most ob.gyns. know little about rheumatic diseases.

“There’s room for education on both sides,” she observed in an interview. “I have had to write letters to gynecologists to get them to put my patients with antiphospholipid antibodies on a contraceptive that includes a progestin because the labeling says, ‘May increase risk of thrombosis.’ And yet if you look at the literature, most of the progestins do not increase the risk of thrombosis, even in patients who are already at increased risk because of a genetic prothrombotic abnormality. I practically had to sign my life away to get a gynecologist to put a progestin-containing IUD in my patient, whereas the risk of thrombosis to my patient with an unplanned pregnancy would have been 10-fold or 100-fold higher. Unplanned pregnancy is dangerous for patients with our diseases.”

And yet, she noted, half of all pregnancies in the United States are unplanned. Among women with rheumatic diseases, the proportion may well be even higher in light of their documented low rate of utilization of effective contraception.

A publication date for the guidelines won’t be set until the review is completed, but the plan is to issue three separate documents. One will address reproductive health outside of pregnancy, with key topics to include contraception, fertility preservation, menopause, and hormone replacement therapy. The second document will focus on pregnancy management, with special attention devoted to women with lupus or antiphospholipid antibodies because they are at particularly high risk of adverse pregnancy outcomes. The third document will be devoted to medications, covering issues including which medications can be continued during pregnancy and when to safely stop the ones that can’t. This section will address both maternal and paternal use of rheumatologic medications, the latter being a topic below the radar of ob.gyns.

The three medications whose paternal use in pregnancy generate the most questions in clinical practice are methotrexate, cyclophosphamide, and sulfasalazine.

“I cannot tell you how many times I’ve been asked whether male patients with rheumatic diseases need to stop their methotrexate before they plan to father a child – that’s been a big one. The answer is they don’t need to stop, but that’s a conditional recommendation because the product label still says to stop it 3 months before. But that’s based on theoretical concerns, and all the data support a lack of teratogenicity for men using methotrexate prior to and during pregnancy,” Dr. Sammaritano said.

Men on cyclophosphamide absolutely have to stop the drug 3 months before pregnancy because the drug causes DNA fragmentation in the sperm. Sulfasalazine is known to impair male fertility. The ACR guidelines will recommend that men continue the drug, but if pregnancy doesn’t occur within a reasonable time, then it’s appropriate to get a semen analysis rather than stopping sulfasalazine unnecessarily.

American College of Obstetricians and Gynecologists guidelines now recommend long-acting reversible contraception, including IUDs and progestin implants, as first-line contraception for all women. The ACR draft guidelines strongly recommend the same.

“That is new. The use of this form of contraception in women with rheumatic diseases is quite low. In general, our patients don’t use contraception as often as other women, and when they do, they don’t use effective contraception. There are many theories as to why that may be: perhaps it’s a focus on the more immediate issues of their rheumatic disease that doesn’t allow their rheumatologist to get to the point of discussing contraception,” according to Dr. Sammaritano.

Many rheumatologists will be pleasantly surprised to learn that the problem of increased risk of pelvic inflammatory disease associated with earlier-generation IUDs is no longer an issue with the current devices. And contrary to a misconception among some ob.gyns., autoimmune disease will not cause a woman to reject her IUD.

The ACR guidelines recommend continuing hydroxychloroquine in lupus patients during pregnancy – and considering starting the drug in those not already on it – because of strong evidence supporting both safety and benefit for mother and baby.

“We are recommending the use of low-dose aspirin for patients with lupus and antiphospholipid antibodies because those two conditions increase the risk for preeclampsia, and the ob.gyns. routinely use low-dose aspirin starting toward the end of the first trimester as preventive therapy. Large studies show that it reduces the risk,” she continued.

Dr. Sammaritano cautioned that the literature on the use of rheumatologic medications in pregnancy and breast feeding is generally weak – and in the case of the new oral small molecule JAK inhibitors, essentially nonexistent.

“A lot of our recommendations are conditional because we did not feel that the data support a strong recommendation. But you have to do something. As long as you communicate the idea that we’re doing the best we can with what information is available, I think patients will respond to that,” the rheumatologist said.

She reported having no financial conflicts regarding her presentation.

[email protected]

CHICAGO – Help is on the way for rheumatologists who may feel out of their depth regarding reproductive health issues in their patients.

Bruce Jancin/MDedge News

“Our patients, fortunately, are pursuing pregnancy more often now than in years past. One of the key messages of the guidelines is that patients really do want to discuss these topics with their rheumatologist, even though that often does not happen now. What patients told us [in the guideline-development process] is their rheumatologist knows them better than their gynecologist or any of their other doctors because we have followed them for a long period of time and we understand their disease and their symptoms. They really want our input on questions about contraception, when to plan a pregnancy, and medication use,” said Dr. Sammaritano of the Hospital for Special Surgery and Cornell University in New York.

The guidelines were created over the course of a year and a half with extensive input from ob.gyns., as well as a patient panel. The project included a systematic review of more than 300 published studies in which guideline panelists attempt to find answers to an initial list of 370 questions. Dr. Sammaritano predicted that the guidelines will prove to be useful not only for rheumatologists, but for their colleagues in ob.gyn. as well. Just as rheumatologists likely haven’t kept up with the sea changes that have occurred in ob.gyn. since their medical school days, most ob.gyns. know little about rheumatic diseases.

“There’s room for education on both sides,” she observed in an interview. “I have had to write letters to gynecologists to get them to put my patients with antiphospholipid antibodies on a contraceptive that includes a progestin because the labeling says, ‘May increase risk of thrombosis.’ And yet if you look at the literature, most of the progestins do not increase the risk of thrombosis, even in patients who are already at increased risk because of a genetic prothrombotic abnormality. I practically had to sign my life away to get a gynecologist to put a progestin-containing IUD in my patient, whereas the risk of thrombosis to my patient with an unplanned pregnancy would have been 10-fold or 100-fold higher. Unplanned pregnancy is dangerous for patients with our diseases.”

And yet, she noted, half of all pregnancies in the United States are unplanned. Among women with rheumatic diseases, the proportion may well be even higher in light of their documented low rate of utilization of effective contraception.

A publication date for the guidelines won’t be set until the review is completed, but the plan is to issue three separate documents. One will address reproductive health outside of pregnancy, with key topics to include contraception, fertility preservation, menopause, and hormone replacement therapy. The second document will focus on pregnancy management, with special attention devoted to women with lupus or antiphospholipid antibodies because they are at particularly high risk of adverse pregnancy outcomes. The third document will be devoted to medications, covering issues including which medications can be continued during pregnancy and when to safely stop the ones that can’t. This section will address both maternal and paternal use of rheumatologic medications, the latter being a topic below the radar of ob.gyns.

The three medications whose paternal use in pregnancy generate the most questions in clinical practice are methotrexate, cyclophosphamide, and sulfasalazine.

“I cannot tell you how many times I’ve been asked whether male patients with rheumatic diseases need to stop their methotrexate before they plan to father a child – that’s been a big one. The answer is they don’t need to stop, but that’s a conditional recommendation because the product label still says to stop it 3 months before. But that’s based on theoretical concerns, and all the data support a lack of teratogenicity for men using methotrexate prior to and during pregnancy,” Dr. Sammaritano said.

Men on cyclophosphamide absolutely have to stop the drug 3 months before pregnancy because the drug causes DNA fragmentation in the sperm. Sulfasalazine is known to impair male fertility. The ACR guidelines will recommend that men continue the drug, but if pregnancy doesn’t occur within a reasonable time, then it’s appropriate to get a semen analysis rather than stopping sulfasalazine unnecessarily.

American College of Obstetricians and Gynecologists guidelines now recommend long-acting reversible contraception, including IUDs and progestin implants, as first-line contraception for all women. The ACR draft guidelines strongly recommend the same.

“That is new. The use of this form of contraception in women with rheumatic diseases is quite low. In general, our patients don’t use contraception as often as other women, and when they do, they don’t use effective contraception. There are many theories as to why that may be: perhaps it’s a focus on the more immediate issues of their rheumatic disease that doesn’t allow their rheumatologist to get to the point of discussing contraception,” according to Dr. Sammaritano.

Many rheumatologists will be pleasantly surprised to learn that the problem of increased risk of pelvic inflammatory disease associated with earlier-generation IUDs is no longer an issue with the current devices. And contrary to a misconception among some ob.gyns., autoimmune disease will not cause a woman to reject her IUD.

The ACR guidelines recommend continuing hydroxychloroquine in lupus patients during pregnancy – and considering starting the drug in those not already on it – because of strong evidence supporting both safety and benefit for mother and baby.

“We are recommending the use of low-dose aspirin for patients with lupus and antiphospholipid antibodies because those two conditions increase the risk for preeclampsia, and the ob.gyns. routinely use low-dose aspirin starting toward the end of the first trimester as preventive therapy. Large studies show that it reduces the risk,” she continued.

Dr. Sammaritano cautioned that the literature on the use of rheumatologic medications in pregnancy and breast feeding is generally weak – and in the case of the new oral small molecule JAK inhibitors, essentially nonexistent.

“A lot of our recommendations are conditional because we did not feel that the data support a strong recommendation. But you have to do something. As long as you communicate the idea that we’re doing the best we can with what information is available, I think patients will respond to that,” the rheumatologist said.

She reported having no financial conflicts regarding her presentation.

[email protected]

CHICAGO – Help is on the way for rheumatologists who may feel out of their depth regarding reproductive health issues in their patients.

Bruce Jancin/MDedge News

“Our patients, fortunately, are pursuing pregnancy more often now than in years past. One of the key messages of the guidelines is that patients really do want to discuss these topics with their rheumatologist, even though that often does not happen now. What patients told us [in the guideline-development process] is their rheumatologist knows them better than their gynecologist or any of their other doctors because we have followed them for a long period of time and we understand their disease and their symptoms. They really want our input on questions about contraception, when to plan a pregnancy, and medication use,” said Dr. Sammaritano of the Hospital for Special Surgery and Cornell University in New York.

The guidelines were created over the course of a year and a half with extensive input from ob.gyns., as well as a patient panel. The project included a systematic review of more than 300 published studies in which guideline panelists attempt to find answers to an initial list of 370 questions. Dr. Sammaritano predicted that the guidelines will prove to be useful not only for rheumatologists, but for their colleagues in ob.gyn. as well. Just as rheumatologists likely haven’t kept up with the sea changes that have occurred in ob.gyn. since their medical school days, most ob.gyns. know little about rheumatic diseases.

“There’s room for education on both sides,” she observed in an interview. “I have had to write letters to gynecologists to get them to put my patients with antiphospholipid antibodies on a contraceptive that includes a progestin because the labeling says, ‘May increase risk of thrombosis.’ And yet if you look at the literature, most of the progestins do not increase the risk of thrombosis, even in patients who are already at increased risk because of a genetic prothrombotic abnormality. I practically had to sign my life away to get a gynecologist to put a progestin-containing IUD in my patient, whereas the risk of thrombosis to my patient with an unplanned pregnancy would have been 10-fold or 100-fold higher. Unplanned pregnancy is dangerous for patients with our diseases.”

And yet, she noted, half of all pregnancies in the United States are unplanned. Among women with rheumatic diseases, the proportion may well be even higher in light of their documented low rate of utilization of effective contraception.

A publication date for the guidelines won’t be set until the review is completed, but the plan is to issue three separate documents. One will address reproductive health outside of pregnancy, with key topics to include contraception, fertility preservation, menopause, and hormone replacement therapy. The second document will focus on pregnancy management, with special attention devoted to women with lupus or antiphospholipid antibodies because they are at particularly high risk of adverse pregnancy outcomes. The third document will be devoted to medications, covering issues including which medications can be continued during pregnancy and when to safely stop the ones that can’t. This section will address both maternal and paternal use of rheumatologic medications, the latter being a topic below the radar of ob.gyns.

The three medications whose paternal use in pregnancy generate the most questions in clinical practice are methotrexate, cyclophosphamide, and sulfasalazine.

“I cannot tell you how many times I’ve been asked whether male patients with rheumatic diseases need to stop their methotrexate before they plan to father a child – that’s been a big one. The answer is they don’t need to stop, but that’s a conditional recommendation because the product label still says to stop it 3 months before. But that’s based on theoretical concerns, and all the data support a lack of teratogenicity for men using methotrexate prior to and during pregnancy,” Dr. Sammaritano said.

Men on cyclophosphamide absolutely have to stop the drug 3 months before pregnancy because the drug causes DNA fragmentation in the sperm. Sulfasalazine is known to impair male fertility. The ACR guidelines will recommend that men continue the drug, but if pregnancy doesn’t occur within a reasonable time, then it’s appropriate to get a semen analysis rather than stopping sulfasalazine unnecessarily.

American College of Obstetricians and Gynecologists guidelines now recommend long-acting reversible contraception, including IUDs and progestin implants, as first-line contraception for all women. The ACR draft guidelines strongly recommend the same.

“That is new. The use of this form of contraception in women with rheumatic diseases is quite low. In general, our patients don’t use contraception as often as other women, and when they do, they don’t use effective contraception. There are many theories as to why that may be: perhaps it’s a focus on the more immediate issues of their rheumatic disease that doesn’t allow their rheumatologist to get to the point of discussing contraception,” according to Dr. Sammaritano.

Many rheumatologists will be pleasantly surprised to learn that the problem of increased risk of pelvic inflammatory disease associated with earlier-generation IUDs is no longer an issue with the current devices. And contrary to a misconception among some ob.gyns., autoimmune disease will not cause a woman to reject her IUD.

The ACR guidelines recommend continuing hydroxychloroquine in lupus patients during pregnancy – and considering starting the drug in those not already on it – because of strong evidence supporting both safety and benefit for mother and baby.

“We are recommending the use of low-dose aspirin for patients with lupus and antiphospholipid antibodies because those two conditions increase the risk for preeclampsia, and the ob.gyns. routinely use low-dose aspirin starting toward the end of the first trimester as preventive therapy. Large studies show that it reduces the risk,” she continued.

Dr. Sammaritano cautioned that the literature on the use of rheumatologic medications in pregnancy and breast feeding is generally weak – and in the case of the new oral small molecule JAK inhibitors, essentially nonexistent.

“A lot of our recommendations are conditional because we did not feel that the data support a strong recommendation. But you have to do something. As long as you communicate the idea that we’re doing the best we can with what information is available, I think patients will respond to that,” the rheumatologist said.

She reported having no financial conflicts regarding her presentation.

[email protected]

Low bone mineral density and the presence of existing spinal syndesmophytes predict the formation of new spinal bony growths and radiographic progression in axial spondyloarthritis (axSpA) at 2 years, according to research conducted by Hyoung Rae Kim of the Catholic University of Korea, Seoul, South Korea, and colleagues.

The investigators noted that low bone mass in ankylosing spondyloarthritis (AS) had been linked in previous studies to spinal structural damage yet “despite the identification of this relationship, it is not yet known whether the presence of low bone mass can independently predict radiographic spinal progression in axSpA patients.”

In order to evaluate the association between low bone mass and the formation of new syndesmophytes and to investigate whether low bone mineral density (BMD) independently predicted radiographic progression in axSpA, the researchers enrolled 119 patients with definite axSpA into their study, published in Arthritis Research & Therapy.

They defined low BMD as z scores of less than or equal to –2.0 and spinal radiographic progression as worsening of the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) by 2 or more points over the 2-year follow-up period.  

Overall, 34 (29%) of the patients had syndesmophytes at baseline, 90 (76%) had radiographic sacroiliitis fulfilling the modified New York criteria for the classification of AS, and 19 (16%) had low BMD.

At 2 years, new syndesmophytes had developed in 22 (21%) of the patients. New syndesmophyte formation occurred in 15% of patients without low BMD and in 37% of patients with low BMD (P = .047).

In the multivariable analysis, current smoking (odds ratio, 3.0; 95% confidence interval, 1.1-7.7), the presence of syndesmophytes (OR, 4.6; 95% CI, 1.8-11.9); and low BMD at baseline (OR, 3.6; 95% CI, 1.2-11.2) were independently associated with significant spinal progression, the investigators reported.

The presence of baseline syndesmophytes and low BMD at any site (OR, 5.5; 95% CI, 2.0-15.2; and OR, 3.6; 95% CI, 1.1-11.8, respectively) was identified by the investigators as significant predictors of new syndesmophytes.

“The presence of a syndesmophyte at baseline and low BMD were predictors of the formation of new syndesmophytes and significant mSASSS progression. … This study is the first to demonstrate that low BMD predicts radiographic progression in axSpA,” they concluded.

The investigators noted that a potential driving mechanism for the ankylosing process was bone loss resulting from chronic inflammation and the associated changes in bone microarchitecture.

“The inflammatory process induces bone loss, which affects the microarchitecture in the trabecular bone, thereby leading to instability. Reduced bone strength triggers a stabilizing anabolic effort that results in bone formation,” they wrote.

“Our results suggest that successful anti-inflammatory treatment reduces inflammation and allows the bone metabolism to normalize, thereby taking away the compensatory anabolic response that leads to new bone formation in the cortical bone of the spine,” they said.

They noted that their study was limited by its small sample and their findings needed confirmation in larger cohorts of axSpA patients.

SOURCE: Arthritis Res Ther. 2018 Oct 16. doi: 10.1186/s13075-018-1731-8.

Low bone mineral density and the presence of existing spinal syndesmophytes predict the formation of new spinal bony growths and radiographic progression in axial spondyloarthritis (axSpA) at 2 years, according to research conducted by Hyoung Rae Kim of the Catholic University of Korea, Seoul, South Korea, and colleagues.

The investigators noted that low bone mass in ankylosing spondyloarthritis (AS) had been linked in previous studies to spinal structural damage yet “despite the identification of this relationship, it is not yet known whether the presence of low bone mass can independently predict radiographic spinal progression in axSpA patients.”

In order to evaluate the association between low bone mass and the formation of new syndesmophytes and to investigate whether low bone mineral density (BMD) independently predicted radiographic progression in axSpA, the researchers enrolled 119 patients with definite axSpA into their study, published in Arthritis Research & Therapy.

They defined low BMD as z scores of less than or equal to –2.0 and spinal radiographic progression as worsening of the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) by 2 or more points over the 2-year follow-up period.  

Overall, 34 (29%) of the patients had syndesmophytes at baseline, 90 (76%) had radiographic sacroiliitis fulfilling the modified New York criteria for the classification of AS, and 19 (16%) had low BMD.

At 2 years, new syndesmophytes had developed in 22 (21%) of the patients. New syndesmophyte formation occurred in 15% of patients without low BMD and in 37% of patients with low BMD (P = .047).

In the multivariable analysis, current smoking (odds ratio, 3.0; 95% confidence interval, 1.1-7.7), the presence of syndesmophytes (OR, 4.6; 95% CI, 1.8-11.9); and low BMD at baseline (OR, 3.6; 95% CI, 1.2-11.2) were independently associated with significant spinal progression, the investigators reported.

The presence of baseline syndesmophytes and low BMD at any site (OR, 5.5; 95% CI, 2.0-15.2; and OR, 3.6; 95% CI, 1.1-11.8, respectively) was identified by the investigators as significant predictors of new syndesmophytes.

“The presence of a syndesmophyte at baseline and low BMD were predictors of the formation of new syndesmophytes and significant mSASSS progression. … This study is the first to demonstrate that low BMD predicts radiographic progression in axSpA,” they concluded.

The investigators noted that a potential driving mechanism for the ankylosing process was bone loss resulting from chronic inflammation and the associated changes in bone microarchitecture.

“The inflammatory process induces bone loss, which affects the microarchitecture in the trabecular bone, thereby leading to instability. Reduced bone strength triggers a stabilizing anabolic effort that results in bone formation,” they wrote.

“Our results suggest that successful anti-inflammatory treatment reduces inflammation and allows the bone metabolism to normalize, thereby taking away the compensatory anabolic response that leads to new bone formation in the cortical bone of the spine,” they said.

They noted that their study was limited by its small sample and their findings needed confirmation in larger cohorts of axSpA patients.

SOURCE: Arthritis Res Ther. 2018 Oct 16. doi: 10.1186/s13075-018-1731-8.

Low bone mineral density and the presence of existing spinal syndesmophytes predict the formation of new spinal bony growths and radiographic progression in axial spondyloarthritis (axSpA) at 2 years, according to research conducted by Hyoung Rae Kim of the Catholic University of Korea, Seoul, South Korea, and colleagues.

The investigators noted that low bone mass in ankylosing spondyloarthritis (AS) had been linked in previous studies to spinal structural damage yet “despite the identification of this relationship, it is not yet known whether the presence of low bone mass can independently predict radiographic spinal progression in axSpA patients.”

In order to evaluate the association between low bone mass and the formation of new syndesmophytes and to investigate whether low bone mineral density (BMD) independently predicted radiographic progression in axSpA, the researchers enrolled 119 patients with definite axSpA into their study, published in Arthritis Research & Therapy.

They defined low BMD as z scores of less than or equal to –2.0 and spinal radiographic progression as worsening of the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) by 2 or more points over the 2-year follow-up period.  

Overall, 34 (29%) of the patients had syndesmophytes at baseline, 90 (76%) had radiographic sacroiliitis fulfilling the modified New York criteria for the classification of AS, and 19 (16%) had low BMD.

At 2 years, new syndesmophytes had developed in 22 (21%) of the patients. New syndesmophyte formation occurred in 15% of patients without low BMD and in 37% of patients with low BMD (P = .047).

In the multivariable analysis, current smoking (odds ratio, 3.0; 95% confidence interval, 1.1-7.7), the presence of syndesmophytes (OR, 4.6; 95% CI, 1.8-11.9); and low BMD at baseline (OR, 3.6; 95% CI, 1.2-11.2) were independently associated with significant spinal progression, the investigators reported.

The presence of baseline syndesmophytes and low BMD at any site (OR, 5.5; 95% CI, 2.0-15.2; and OR, 3.6; 95% CI, 1.1-11.8, respectively) was identified by the investigators as significant predictors of new syndesmophytes.

“The presence of a syndesmophyte at baseline and low BMD were predictors of the formation of new syndesmophytes and significant mSASSS progression. … This study is the first to demonstrate that low BMD predicts radiographic progression in axSpA,” they concluded.

The investigators noted that a potential driving mechanism for the ankylosing process was bone loss resulting from chronic inflammation and the associated changes in bone microarchitecture.

“The inflammatory process induces bone loss, which affects the microarchitecture in the trabecular bone, thereby leading to instability. Reduced bone strength triggers a stabilizing anabolic effort that results in bone formation,” they wrote.

“Our results suggest that successful anti-inflammatory treatment reduces inflammation and allows the bone metabolism to normalize, thereby taking away the compensatory anabolic response that leads to new bone formation in the cortical bone of the spine,” they said.

They noted that their study was limited by its small sample and their findings needed confirmation in larger cohorts of axSpA patients.

SOURCE: Arthritis Res Ther. 2018 Oct 16. doi: 10.1186/s13075-018-1731-8.

Pregnancy registries are valuable sources of information. For many drugs, they are the primary source of the human pregnancy experience. However, although most of the registries use the word “pregnancy,” it is important to note that many also enroll women who took the target drug shortly before conception.

Antonio_Diaz/Thinkstock

The strengths of these registries are their prospective nature (enrolled before the outcome is known) and enrollment over a wide geographical area. Typically, two types of pregnancy outcomes are obtained: those with birth defects and those without known birth defects (classified as live births, fetal deaths, and spontaneous abortions). Registries can identify early signals of teratogenicity, but they have several limitations: selection bias that results from voluntary reporting; target populations that are not representative; lost-to-follow-up pregnancies that may have had different outcomes than those with documented outcomes; elective terminations and fetal deaths without birth defects and spontaneous abortions, all of which may lack details; the lack of control groups (with some exceptions); and the publication of results that may be delayed or not be in a peer-reviewed journal. Because the total number of exposed pregnancies is unknown, the data cannot be used to calculate prevalences, but they can be used to estimate the proportion of birth defects. Some registries also collect data on retrospective reports (reported after outcome is known). Such reports are less representative of the target population because they can be biased toward the reporting of more unusual and severe outcomes. But they may be helpful in detecting unusual patterns of birth defects.

For the following drugs, web addresses can be obtained from the Food and Drug Administration website, List of Pregnancy Exposure Registries.

MotherToBaby

A large registry, the MotherToBaby Organization of Teratology Information Specialists (OTIS) (877-311-8972), involves patients in several different categories and the effects of the drugs on the embryo-fetus: autoimmune diseases (ankylosing spondylitis, rheumatoid arthritis, psoriatic arthritis, ulcerative colitis, psoriasis, Crohn’s disease, and multiple sclerosis); asthma at less than 20 weeks’ gestation; vaccines; and heterozygous or homozygous familial hypercholesterolemia.

For the autoimmune diseases, the drugs and trade names are abatacept (Orencia), adalimumab (Humira), certolizumab pegol (Cimzia), etanercept (Enbrel), infliximab (Remicade), leflunomide (Arava), otezla (Apremilast), teriflunomide (Aubagio), tocilizumab (Actemra), tofacitinib (Xeljanz), and ustekinumab (Stelara).

For the asthma group, the drug being investigated is mepolizumab (Nucala).

Two vaccines – for tetanus, diphtheria, and pertussis (Tdap) and meningococcal disease caused by Neisseria meningitidis serogroups A, C, Y and W-135 (Menveo) – are being studied.

The last category is heterozygous or homozygous familial hypercholesterolemia. The two agents in this category are alirocumab (Praluent) and evolocumab (Repatha).
 

Other registries

Breast cancer

The Mother Pregnancy Registry, INC Research (800-690-6720), is enrolling breast cancer patients who have been treated during pregnancy with ado-trastuzumab emtansine (Kadcyla), pertuzumab (Perjeta), or trastuzumab (Herceptin).



Epilepsy

The Antiepileptic Drug Pregnancy registry (888-233-2334) is studying eslicarbazepine (Aptiom) and pregabalin (Lyrica).



Fabry disease

The Fabry Registry, Genzyme Corp (617-591-5500) is studying the use in pregnancy of agalsidase beta (Fabrazyme) for Fabry disease.



Fibromyalgia

The Savella Pregnancy Registry (877-643-3010) is looking for patients with fibromyalgia who are being treated with milnacipran (Savella).



Hepatitis B

The Ribavirin Pregnancy Registry, INC Research (800-593-2214) is looking for subjects with hepatitis C who have been treated with ribavirin (Copegus).



Hypercholesterolemia

Lomitapide (Juxtapid) is being studied by the Global Lomitapide Pregnancy Exposure Registry managed by Aegerion (877-902-4099). The drug is used for homozygous familial hypercholesterolemia.



Mucopolysaccharidosis

The Mucopolysaccharidosis I (MPS I) registry, Genzyme (617-591-5500) is studying the use of laronidase (Aldurazyme) for Hurler syndrome, Scheie syndrome, and Hurler-Scheie syndrome.

The use of galsulfase (Naglazyme) for Maroteaux-Lamy syndrome during pregnancy is under study by the Mucopolysaccharidosis VI (MPS VI), clinical surveillance program (BioMarin Pharmaceutical) (415-506-6849 or 415-506-6703).

Multiple sclerosis

Novartis is conducting the Gilenya Pregnancy Registry (877-598-7237) for patients with multiple sclerosis who are taking fingolimod (Gilenya).

Alemtuzumab (Lemtrada), also indicated for multiple sclerosis, is the target agent for the LEMTRADA Pregnancy Exposure Registry (866-758-2990).

Narcolepsy and other sleep disorders

Armodafinil (Nuvigil), used for excessive sleepiness associated with narcolepsy and other sleep disorders, is being studied in the Nuvigil Pregnancy Registry (866-404-4106). A second drug with the same indication and telephone number, modafinil (Provigil), is in the Provigil Pregnancy Registry.



Osteoporosis

Amgen’s Pregnancy Surveillance Program (800-772-6436) is enrolling pregnant subjects with osteoporosis who are being treated with denosumab (Prolia).



Others

Two Merck pregnancy registries (800-986-8999) cover the following conditions: type 2 diabetes sitagliptin+metformin (Janumet) or sitagliptin (Januvia); and migraine headaches rizatriptan (Maxalt).

GlaxoSmithKline is conducting two registries: the Belimumab Pregnancy Registry for patients with systemic lupus erythematosus treated with belimumab (Benlysta) (877-681-6296); and Promacta Pregnancy Registry for women treated for thrombocytopenia with eltrombopag (Promacta) (888-825-5249).
 

Psychiatric Drugs

The National Pregnancy Registry for Atypical Antipsychotics (866-961-2388) is studying 10 drugs: aripiprazole (Abilify), asenapine (Saphris), clozapine (Clozaril), iloperidone (Fanapt), lurasidone (Latuda), olanzapine (Zyprexa), paliperidone (Invega), quetiapine (Seroquel), risperidone (Risperdal), and ziprasidone (Geodon).

The National Pregnancy Registry for Antidepressants (844-405-6185) is studying amitriptyline (Elavil), amoxapine (Asendin), bupropion (Forfivo XL and Wellbutrin), citalopram (Celexa), clomipramine (Anafranil), desipramine (Norpramin), desvenlafaxine (Prisiq), doxepin (Sinequan), escitalopram (Lexapro), fluvoxamine (Luvox), fluoxetine (Prozac), imipramine (Tofranil), isocarboxazid (Marplan), levomilnacipran (Fetzima), maprotiline (Ludiomil), mirtazapine (Remeron), nefazodone (Serzone), nortriptyline (Pamelor), paroxetine (Paxil), phenelzine (Nardill), protriptyline (Vivactil), selegiline (Emsam), sertraline (Zoloft), tranylcypromine (Pamate), trazodone (Desyrel), trimipramine (Surmontil), venlafaxine (Effexor), and vilazodone (Viibryd).

The National Pregnancy Registry of Psychostimulants (866-961-2388) is studying amphetamine (Adderall), dextroamphetamine (Dexedrine and Focalin), lisdexamfetamine (Vyvanse), methylphenidate (Concerta, Daytrana, Desoxyn, Ritalin), and modafinil (Provigil).

The antidepressant duloxetine (Cymbalta) is being studied by the Cymbalta Pregnancy Registry (866-814-6975).

Transplant patients

Renal transplant patients exposed to mycophenolate (CellCept) can be enrolled in the Transplantation Pregnancy Registry International (877-955-6877) or the Mycophenolate Pregnancy Registry (800-617-8191). The Transplantation Pregnancy Registry International also is enrolling renal transplant patients exposed to belatacept (Nulojix).



Vaccines

A quadrivalent influenza vaccine (Afluria) is being studied by the Seqirus Influenza Vaccine Pregnancy Registry (855-358-8972). A second vaccine for meningococcal disease meningococcal disease caused by Neisseria meningitidis serogroups A, C, Y and W-135 (Menactra) is under study by the Menactra Vaccine Pregnancy Registry (800-822-2463). The Bexsero Pregnancy Registry (877-413-4759) is open to patients who have received the meningococcal group B vaccine (Bexsero). The Hepatitis B Vaccine [Recombinant] Adjuvanted Pregnancy Registry, also listed as HEPLISAV-B, is enrolling patients who have received that vaccine (844-443-7734); it is supported by the Dynavax Technologies Corporation.

Mr. Briggs is clinical professor of pharmacy at the University of California, San Francisco, and adjunct professor of pharmacy at the University of Southern California, Los Angeles, as well as at Washington State University, Spokane. Mr. Briggs said he had no relevant financial disclosures. Email him at [email protected].

Pregnancy registries are valuable sources of information. For many drugs, they are the primary source of the human pregnancy experience. However, although most of the registries use the word “pregnancy,” it is important to note that many also enroll women who took the target drug shortly before conception.

Antonio_Diaz/Thinkstock

The strengths of these registries are their prospective nature (enrolled before the outcome is known) and enrollment over a wide geographical area. Typically, two types of pregnancy outcomes are obtained: those with birth defects and those without known birth defects (classified as live births, fetal deaths, and spontaneous abortions). Registries can identify early signals of teratogenicity, but they have several limitations: selection bias that results from voluntary reporting; target populations that are not representative; lost-to-follow-up pregnancies that may have had different outcomes than those with documented outcomes; elective terminations and fetal deaths without birth defects and spontaneous abortions, all of which may lack details; the lack of control groups (with some exceptions); and the publication of results that may be delayed or not be in a peer-reviewed journal. Because the total number of exposed pregnancies is unknown, the data cannot be used to calculate prevalences, but they can be used to estimate the proportion of birth defects. Some registries also collect data on retrospective reports (reported after outcome is known). Such reports are less representative of the target population because they can be biased toward the reporting of more unusual and severe outcomes. But they may be helpful in detecting unusual patterns of birth defects.

For the following drugs, web addresses can be obtained from the Food and Drug Administration website, List of Pregnancy Exposure Registries.

MotherToBaby

A large registry, the MotherToBaby Organization of Teratology Information Specialists (OTIS) (877-311-8972), involves patients in several different categories and the effects of the drugs on the embryo-fetus: autoimmune diseases (ankylosing spondylitis, rheumatoid arthritis, psoriatic arthritis, ulcerative colitis, psoriasis, Crohn’s disease, and multiple sclerosis); asthma at less than 20 weeks’ gestation; vaccines; and heterozygous or homozygous familial hypercholesterolemia.

For the autoimmune diseases, the drugs and trade names are abatacept (Orencia), adalimumab (Humira), certolizumab pegol (Cimzia), etanercept (Enbrel), infliximab (Remicade), leflunomide (Arava), otezla (Apremilast), teriflunomide (Aubagio), tocilizumab (Actemra), tofacitinib (Xeljanz), and ustekinumab (Stelara).

For the asthma group, the drug being investigated is mepolizumab (Nucala).

Two vaccines – for tetanus, diphtheria, and pertussis (Tdap) and meningococcal disease caused by Neisseria meningitidis serogroups A, C, Y and W-135 (Menveo) – are being studied.

The last category is heterozygous or homozygous familial hypercholesterolemia. The two agents in this category are alirocumab (Praluent) and evolocumab (Repatha).
 

Other registries

Breast cancer

The Mother Pregnancy Registry, INC Research (800-690-6720), is enrolling breast cancer patients who have been treated during pregnancy with ado-trastuzumab emtansine (Kadcyla), pertuzumab (Perjeta), or trastuzumab (Herceptin).



Epilepsy

The Antiepileptic Drug Pregnancy registry (888-233-2334) is studying eslicarbazepine (Aptiom) and pregabalin (Lyrica).



Fabry disease

The Fabry Registry, Genzyme Corp (617-591-5500) is studying the use in pregnancy of agalsidase beta (Fabrazyme) for Fabry disease.



Fibromyalgia

The Savella Pregnancy Registry (877-643-3010) is looking for patients with fibromyalgia who are being treated with milnacipran (Savella).



Hepatitis B

The Ribavirin Pregnancy Registry, INC Research (800-593-2214) is looking for subjects with hepatitis C who have been treated with ribavirin (Copegus).



Hypercholesterolemia

Lomitapide (Juxtapid) is being studied by the Global Lomitapide Pregnancy Exposure Registry managed by Aegerion (877-902-4099). The drug is used for homozygous familial hypercholesterolemia.



Mucopolysaccharidosis

The Mucopolysaccharidosis I (MPS I) registry, Genzyme (617-591-5500) is studying the use of laronidase (Aldurazyme) for Hurler syndrome, Scheie syndrome, and Hurler-Scheie syndrome.

The use of galsulfase (Naglazyme) for Maroteaux-Lamy syndrome during pregnancy is under study by the Mucopolysaccharidosis VI (MPS VI), clinical surveillance program (BioMarin Pharmaceutical) (415-506-6849 or 415-506-6703).

Multiple sclerosis

Novartis is conducting the Gilenya Pregnancy Registry (877-598-7237) for patients with multiple sclerosis who are taking fingolimod (Gilenya).

Alemtuzumab (Lemtrada), also indicated for multiple sclerosis, is the target agent for the LEMTRADA Pregnancy Exposure Registry (866-758-2990).

Narcolepsy and other sleep disorders

Armodafinil (Nuvigil), used for excessive sleepiness associated with narcolepsy and other sleep disorders, is being studied in the Nuvigil Pregnancy Registry (866-404-4106). A second drug with the same indication and telephone number, modafinil (Provigil), is in the Provigil Pregnancy Registry.



Osteoporosis

Amgen’s Pregnancy Surveillance Program (800-772-6436) is enrolling pregnant subjects with osteoporosis who are being treated with denosumab (Prolia).



Others

Two Merck pregnancy registries (800-986-8999) cover the following conditions: type 2 diabetes sitagliptin+metformin (Janumet) or sitagliptin (Januvia); and migraine headaches rizatriptan (Maxalt).

GlaxoSmithKline is conducting two registries: the Belimumab Pregnancy Registry for patients with systemic lupus erythematosus treated with belimumab (Benlysta) (877-681-6296); and Promacta Pregnancy Registry for women treated for thrombocytopenia with eltrombopag (Promacta) (888-825-5249).
 

Psychiatric Drugs

The National Pregnancy Registry for Atypical Antipsychotics (866-961-2388) is studying 10 drugs: aripiprazole (Abilify), asenapine (Saphris), clozapine (Clozaril), iloperidone (Fanapt), lurasidone (Latuda), olanzapine (Zyprexa), paliperidone (Invega), quetiapine (Seroquel), risperidone (Risperdal), and ziprasidone (Geodon).

The National Pregnancy Registry for Antidepressants (844-405-6185) is studying amitriptyline (Elavil), amoxapine (Asendin), bupropion (Forfivo XL and Wellbutrin), citalopram (Celexa), clomipramine (Anafranil), desipramine (Norpramin), desvenlafaxine (Prisiq), doxepin (Sinequan), escitalopram (Lexapro), fluvoxamine (Luvox), fluoxetine (Prozac), imipramine (Tofranil), isocarboxazid (Marplan), levomilnacipran (Fetzima), maprotiline (Ludiomil), mirtazapine (Remeron), nefazodone (Serzone), nortriptyline (Pamelor), paroxetine (Paxil), phenelzine (Nardill), protriptyline (Vivactil), selegiline (Emsam), sertraline (Zoloft), tranylcypromine (Pamate), trazodone (Desyrel), trimipramine (Surmontil), venlafaxine (Effexor), and vilazodone (Viibryd).

The National Pregnancy Registry of Psychostimulants (866-961-2388) is studying amphetamine (Adderall), dextroamphetamine (Dexedrine and Focalin), lisdexamfetamine (Vyvanse), methylphenidate (Concerta, Daytrana, Desoxyn, Ritalin), and modafinil (Provigil).

The antidepressant duloxetine (Cymbalta) is being studied by the Cymbalta Pregnancy Registry (866-814-6975).

Transplant patients

Renal transplant patients exposed to mycophenolate (CellCept) can be enrolled in the Transplantation Pregnancy Registry International (877-955-6877) or the Mycophenolate Pregnancy Registry (800-617-8191). The Transplantation Pregnancy Registry International also is enrolling renal transplant patients exposed to belatacept (Nulojix).



Vaccines

A quadrivalent influenza vaccine (Afluria) is being studied by the Seqirus Influenza Vaccine Pregnancy Registry (855-358-8972). A second vaccine for meningococcal disease meningococcal disease caused by Neisseria meningitidis serogroups A, C, Y and W-135 (Menactra) is under study by the Menactra Vaccine Pregnancy Registry (800-822-2463). The Bexsero Pregnancy Registry (877-413-4759) is open to patients who have received the meningococcal group B vaccine (Bexsero). The Hepatitis B Vaccine [Recombinant] Adjuvanted Pregnancy Registry, also listed as HEPLISAV-B, is enrolling patients who have received that vaccine (844-443-7734); it is supported by the Dynavax Technologies Corporation.

Mr. Briggs is clinical professor of pharmacy at the University of California, San Francisco, and adjunct professor of pharmacy at the University of Southern California, Los Angeles, as well as at Washington State University, Spokane. Mr. Briggs said he had no relevant financial disclosures. Email him at [email protected].

Pregnancy registries are valuable sources of information. For many drugs, they are the primary source of the human pregnancy experience. However, although most of the registries use the word “pregnancy,” it is important to note that many also enroll women who took the target drug shortly before conception.

Antonio_Diaz/Thinkstock

The strengths of these registries are their prospective nature (enrolled before the outcome is known) and enrollment over a wide geographical area. Typically, two types of pregnancy outcomes are obtained: those with birth defects and those without known birth defects (classified as live births, fetal deaths, and spontaneous abortions). Registries can identify early signals of teratogenicity, but they have several limitations: selection bias that results from voluntary reporting; target populations that are not representative; lost-to-follow-up pregnancies that may have had different outcomes than those with documented outcomes; elective terminations and fetal deaths without birth defects and spontaneous abortions, all of which may lack details; the lack of control groups (with some exceptions); and the publication of results that may be delayed or not be in a peer-reviewed journal. Because the total number of exposed pregnancies is unknown, the data cannot be used to calculate prevalences, but they can be used to estimate the proportion of birth defects. Some registries also collect data on retrospective reports (reported after outcome is known). Such reports are less representative of the target population because they can be biased toward the reporting of more unusual and severe outcomes. But they may be helpful in detecting unusual patterns of birth defects.

For the following drugs, web addresses can be obtained from the Food and Drug Administration website, List of Pregnancy Exposure Registries.

MotherToBaby

A large registry, the MotherToBaby Organization of Teratology Information Specialists (OTIS) (877-311-8972), involves patients in several different categories and the effects of the drugs on the embryo-fetus: autoimmune diseases (ankylosing spondylitis, rheumatoid arthritis, psoriatic arthritis, ulcerative colitis, psoriasis, Crohn’s disease, and multiple sclerosis); asthma at less than 20 weeks’ gestation; vaccines; and heterozygous or homozygous familial hypercholesterolemia.

For the autoimmune diseases, the drugs and trade names are abatacept (Orencia), adalimumab (Humira), certolizumab pegol (Cimzia), etanercept (Enbrel), infliximab (Remicade), leflunomide (Arava), otezla (Apremilast), teriflunomide (Aubagio), tocilizumab (Actemra), tofacitinib (Xeljanz), and ustekinumab (Stelara).

For the asthma group, the drug being investigated is mepolizumab (Nucala).

Two vaccines – for tetanus, diphtheria, and pertussis (Tdap) and meningococcal disease caused by Neisseria meningitidis serogroups A, C, Y and W-135 (Menveo) – are being studied.

The last category is heterozygous or homozygous familial hypercholesterolemia. The two agents in this category are alirocumab (Praluent) and evolocumab (Repatha).
 

Other registries

Breast cancer

The Mother Pregnancy Registry, INC Research (800-690-6720), is enrolling breast cancer patients who have been treated during pregnancy with ado-trastuzumab emtansine (Kadcyla), pertuzumab (Perjeta), or trastuzumab (Herceptin).



Epilepsy

The Antiepileptic Drug Pregnancy registry (888-233-2334) is studying eslicarbazepine (Aptiom) and pregabalin (Lyrica).



Fabry disease

The Fabry Registry, Genzyme Corp (617-591-5500) is studying the use in pregnancy of agalsidase beta (Fabrazyme) for Fabry disease.



Fibromyalgia

The Savella Pregnancy Registry (877-643-3010) is looking for patients with fibromyalgia who are being treated with milnacipran (Savella).



Hepatitis B

The Ribavirin Pregnancy Registry, INC Research (800-593-2214) is looking for subjects with hepatitis C who have been treated with ribavirin (Copegus).



Hypercholesterolemia

Lomitapide (Juxtapid) is being studied by the Global Lomitapide Pregnancy Exposure Registry managed by Aegerion (877-902-4099). The drug is used for homozygous familial hypercholesterolemia.



Mucopolysaccharidosis

The Mucopolysaccharidosis I (MPS I) registry, Genzyme (617-591-5500) is studying the use of laronidase (Aldurazyme) for Hurler syndrome, Scheie syndrome, and Hurler-Scheie syndrome.

The use of galsulfase (Naglazyme) for Maroteaux-Lamy syndrome during pregnancy is under study by the Mucopolysaccharidosis VI (MPS VI), clinical surveillance program (BioMarin Pharmaceutical) (415-506-6849 or 415-506-6703).

Multiple sclerosis

Novartis is conducting the Gilenya Pregnancy Registry (877-598-7237) for patients with multiple sclerosis who are taking fingolimod (Gilenya).

Alemtuzumab (Lemtrada), also indicated for multiple sclerosis, is the target agent for the LEMTRADA Pregnancy Exposure Registry (866-758-2990).

Narcolepsy and other sleep disorders

Armodafinil (Nuvigil), used for excessive sleepiness associated with narcolepsy and other sleep disorders, is being studied in the Nuvigil Pregnancy Registry (866-404-4106). A second drug with the same indication and telephone number, modafinil (Provigil), is in the Provigil Pregnancy Registry.



Osteoporosis

Amgen’s Pregnancy Surveillance Program (800-772-6436) is enrolling pregnant subjects with osteoporosis who are being treated with denosumab (Prolia).



Others

Two Merck pregnancy registries (800-986-8999) cover the following conditions: type 2 diabetes sitagliptin+metformin (Janumet) or sitagliptin (Januvia); and migraine headaches rizatriptan (Maxalt).

GlaxoSmithKline is conducting two registries: the Belimumab Pregnancy Registry for patients with systemic lupus erythematosus treated with belimumab (Benlysta) (877-681-6296); and Promacta Pregnancy Registry for women treated for thrombocytopenia with eltrombopag (Promacta) (888-825-5249).
 

Psychiatric Drugs

The National Pregnancy Registry for Atypical Antipsychotics (866-961-2388) is studying 10 drugs: aripiprazole (Abilify), asenapine (Saphris), clozapine (Clozaril), iloperidone (Fanapt), lurasidone (Latuda), olanzapine (Zyprexa), paliperidone (Invega), quetiapine (Seroquel), risperidone (Risperdal), and ziprasidone (Geodon).

The National Pregnancy Registry for Antidepressants (844-405-6185) is studying amitriptyline (Elavil), amoxapine (Asendin), bupropion (Forfivo XL and Wellbutrin), citalopram (Celexa), clomipramine (Anafranil), desipramine (Norpramin), desvenlafaxine (Prisiq), doxepin (Sinequan), escitalopram (Lexapro), fluvoxamine (Luvox), fluoxetine (Prozac), imipramine (Tofranil), isocarboxazid (Marplan), levomilnacipran (Fetzima), maprotiline (Ludiomil), mirtazapine (Remeron), nefazodone (Serzone), nortriptyline (Pamelor), paroxetine (Paxil), phenelzine (Nardill), protriptyline (Vivactil), selegiline (Emsam), sertraline (Zoloft), tranylcypromine (Pamate), trazodone (Desyrel), trimipramine (Surmontil), venlafaxine (Effexor), and vilazodone (Viibryd).

The National Pregnancy Registry of Psychostimulants (866-961-2388) is studying amphetamine (Adderall), dextroamphetamine (Dexedrine and Focalin), lisdexamfetamine (Vyvanse), methylphenidate (Concerta, Daytrana, Desoxyn, Ritalin), and modafinil (Provigil).

The antidepressant duloxetine (Cymbalta) is being studied by the Cymbalta Pregnancy Registry (866-814-6975).

Transplant patients

Renal transplant patients exposed to mycophenolate (CellCept) can be enrolled in the Transplantation Pregnancy Registry International (877-955-6877) or the Mycophenolate Pregnancy Registry (800-617-8191). The Transplantation Pregnancy Registry International also is enrolling renal transplant patients exposed to belatacept (Nulojix).



Vaccines

A quadrivalent influenza vaccine (Afluria) is being studied by the Seqirus Influenza Vaccine Pregnancy Registry (855-358-8972). A second vaccine for meningococcal disease meningococcal disease caused by Neisseria meningitidis serogroups A, C, Y and W-135 (Menactra) is under study by the Menactra Vaccine Pregnancy Registry (800-822-2463). The Bexsero Pregnancy Registry (877-413-4759) is open to patients who have received the meningococcal group B vaccine (Bexsero). The Hepatitis B Vaccine [Recombinant] Adjuvanted Pregnancy Registry, also listed as HEPLISAV-B, is enrolling patients who have received that vaccine (844-443-7734); it is supported by the Dynavax Technologies Corporation.

Mr. Briggs is clinical professor of pharmacy at the University of California, San Francisco, and adjunct professor of pharmacy at the University of Southern California, Los Angeles, as well as at Washington State University, Spokane. Mr. Briggs said he had no relevant financial disclosures. Email him at [email protected].