SAN DIEGO – Researchers say they’ve developed a novel blood-based assay that can differentiate patients with seropositive or seronegative rheumatoid arthritis from healthy people and those with other inflammatory diseases or osteoarthritis.

While cautioning that the results need to be confirmed, University of Oxford (England) rheumatologist Peter Taylor, PhD, MA, told an audience at the annual meeting of the American College of Rheumatology that the test has an overall mean sensitivity of 90.8% (standard deviation, 0.94%; 95% confidence interval, 83.2%-95.4%) and mean specificity of 96.1% (SD, 0.64%; 95% CI, 92.7%-97.9%). The mean area under the curve (AUC) is 0.991 (SD, 0.001; 95% CI, 97.2%-99.6%).

SAN DIEGO – Researchers say they’ve developed a novel blood-based assay that can differentiate patients with seropositive or seronegative rheumatoid arthritis from healthy people and those with other inflammatory diseases or osteoarthritis.

While cautioning that the results need to be confirmed, University of Oxford (England) rheumatologist Peter Taylor, PhD, MA, told an audience at the annual meeting of the American College of Rheumatology that the test has an overall mean sensitivity of 90.8% (standard deviation, 0.94%; 95% confidence interval, 83.2%-95.4%) and mean specificity of 96.1% (SD, 0.64%; 95% CI, 92.7%-97.9%). The mean area under the curve (AUC) is 0.991 (SD, 0.001; 95% CI, 97.2%-99.6%).

SAN DIEGO – Researchers say they’ve developed a novel blood-based assay that can differentiate patients with seropositive or seronegative rheumatoid arthritis from healthy people and those with other inflammatory diseases or osteoarthritis.

While cautioning that the results need to be confirmed, University of Oxford (England) rheumatologist Peter Taylor, PhD, MA, told an audience at the annual meeting of the American College of Rheumatology that the test has an overall mean sensitivity of 90.8% (standard deviation, 0.94%; 95% confidence interval, 83.2%-95.4%) and mean specificity of 96.1% (SD, 0.64%; 95% CI, 92.7%-97.9%). The mean area under the curve (AUC) is 0.991 (SD, 0.001; 95% CI, 97.2%-99.6%).

The patient was given a diagnosis of sialadenosis (also known as sialosis), a noninflammatory, non-neoplastic enlargement of the parotid glands. It can often manifest as fatty degeneration of the parotid glands, which may be associated with underlying conditions such as hypertriglyceridemia, diabetes, and metabolic syndrome.^1-3

Ultrasonography and a subsequent computed tomography with contrast demonstrated fatty hypertrophy of the parotid glands without any concerning parotid mass or enlarged cervical lymph nodes. No abnormalities of the ductal system (eg, stricture or obstruction with stone) were noted, so sialography and sialendoscopy were not indicated.

Evaluation for inflammatory, autoimmune, and granulomatous diseases was negative, including negative anti-Ro/SSA and anti-La/SSB antibodies and negative HIV screen. However, our patient had an elevated serum triglyceride level of 589 mg/dL (reference range, < 150 mg/dL), while serum total cholesterol was within the reference range (< 200 mg/dL). (Interestingly, his triglycerides were normal a year earlier.) The patient’s A1c level was normal.

The differential diagnosis for this patient included Sjögren syndrome, abscess, viral infection (eg, mumps, HIV sialopathy), Kimura disease, sarcoidosis, masseter hypertrophy, and tumors of the parotid gland (eg, Warthin tumor and pleomorphic adenoma). Drug-induced sialadenitis was another possibility, as several drugs may be associated with salivary gland enlargement.⁴ However, no association was found for our patient.

Primary management is focused on treating the underlying disorder. The application of heat, massage, and sialagogues (eg, pilocarpine 5 mg orally tid) can be used to stimulate salivation, which may help reduce the swelling. Bilateral parotid gland swelling in patients with increased triglyceride levels often resolves after treatment of hypertriglyceridemia.^3,5 Less common modalities include botulinum neurotoxin injection, tympanic neurectomy, and parotidectomy.⁶

The treatment plan for this patient included aggressive dietary modification and increasing his current dosage of atorvastatin from 20 mg to 80 mg at bedtime. Increasing the dosage of statin was preferred over adding another agent (such as fibrates) to decrease the risk of myopathy. Fine-needle aspiration biopsy may be considered if the swelling does not resolve after correction of lipid abnormalities, which can take between 6 months and 3 years.³

‌

Photo courtesy of Faryal Tahir, MD. Text courtesy of Faryal Tahir, MD, Assistant Professor, and Daniel Stulberg, MD, FAAFP, Professor and Chair, Department of Family and Community Medicine, Western Michigan University, Homer Stryker, MD School of Medicine, Kalamazoo.

The patient was given a diagnosis of sialadenosis (also known as sialosis), a noninflammatory, non-neoplastic enlargement of the parotid glands. It can often manifest as fatty degeneration of the parotid glands, which may be associated with underlying conditions such as hypertriglyceridemia, diabetes, and metabolic syndrome.^1-3

Ultrasonography and a subsequent computed tomography with contrast demonstrated fatty hypertrophy of the parotid glands without any concerning parotid mass or enlarged cervical lymph nodes. No abnormalities of the ductal system (eg, stricture or obstruction with stone) were noted, so sialography and sialendoscopy were not indicated.

Evaluation for inflammatory, autoimmune, and granulomatous diseases was negative, including negative anti-Ro/SSA and anti-La/SSB antibodies and negative HIV screen. However, our patient had an elevated serum triglyceride level of 589 mg/dL (reference range, < 150 mg/dL), while serum total cholesterol was within the reference range (< 200 mg/dL). (Interestingly, his triglycerides were normal a year earlier.) The patient’s A1c level was normal.

The differential diagnosis for this patient included Sjögren syndrome, abscess, viral infection (eg, mumps, HIV sialopathy), Kimura disease, sarcoidosis, masseter hypertrophy, and tumors of the parotid gland (eg, Warthin tumor and pleomorphic adenoma). Drug-induced sialadenitis was another possibility, as several drugs may be associated with salivary gland enlargement.⁴ However, no association was found for our patient.

Primary management is focused on treating the underlying disorder. The application of heat, massage, and sialagogues (eg, pilocarpine 5 mg orally tid) can be used to stimulate salivation, which may help reduce the swelling. Bilateral parotid gland swelling in patients with increased triglyceride levels often resolves after treatment of hypertriglyceridemia.^3,5 Less common modalities include botulinum neurotoxin injection, tympanic neurectomy, and parotidectomy.⁶

The treatment plan for this patient included aggressive dietary modification and increasing his current dosage of atorvastatin from 20 mg to 80 mg at bedtime. Increasing the dosage of statin was preferred over adding another agent (such as fibrates) to decrease the risk of myopathy. Fine-needle aspiration biopsy may be considered if the swelling does not resolve after correction of lipid abnormalities, which can take between 6 months and 3 years.³

‌

Photo courtesy of Faryal Tahir, MD. Text courtesy of Faryal Tahir, MD, Assistant Professor, and Daniel Stulberg, MD, FAAFP, Professor and Chair, Department of Family and Community Medicine, Western Michigan University, Homer Stryker, MD School of Medicine, Kalamazoo.

The patient was given a diagnosis of sialadenosis (also known as sialosis), a noninflammatory, non-neoplastic enlargement of the parotid glands. It can often manifest as fatty degeneration of the parotid glands, which may be associated with underlying conditions such as hypertriglyceridemia, diabetes, and metabolic syndrome.^1-3

Ultrasonography and a subsequent computed tomography with contrast demonstrated fatty hypertrophy of the parotid glands without any concerning parotid mass or enlarged cervical lymph nodes. No abnormalities of the ductal system (eg, stricture or obstruction with stone) were noted, so sialography and sialendoscopy were not indicated.

Evaluation for inflammatory, autoimmune, and granulomatous diseases was negative, including negative anti-Ro/SSA and anti-La/SSB antibodies and negative HIV screen. However, our patient had an elevated serum triglyceride level of 589 mg/dL (reference range, < 150 mg/dL), while serum total cholesterol was within the reference range (< 200 mg/dL). (Interestingly, his triglycerides were normal a year earlier.) The patient’s A1c level was normal.

The differential diagnosis for this patient included Sjögren syndrome, abscess, viral infection (eg, mumps, HIV sialopathy), Kimura disease, sarcoidosis, masseter hypertrophy, and tumors of the parotid gland (eg, Warthin tumor and pleomorphic adenoma). Drug-induced sialadenitis was another possibility, as several drugs may be associated with salivary gland enlargement.⁴ However, no association was found for our patient.

Primary management is focused on treating the underlying disorder. The application of heat, massage, and sialagogues (eg, pilocarpine 5 mg orally tid) can be used to stimulate salivation, which may help reduce the swelling. Bilateral parotid gland swelling in patients with increased triglyceride levels often resolves after treatment of hypertriglyceridemia.^3,5 Less common modalities include botulinum neurotoxin injection, tympanic neurectomy, and parotidectomy.⁶

The treatment plan for this patient included aggressive dietary modification and increasing his current dosage of atorvastatin from 20 mg to 80 mg at bedtime. Increasing the dosage of statin was preferred over adding another agent (such as fibrates) to decrease the risk of myopathy. Fine-needle aspiration biopsy may be considered if the swelling does not resolve after correction of lipid abnormalities, which can take between 6 months and 3 years.³

‌

Photo courtesy of Faryal Tahir, MD. Text courtesy of Faryal Tahir, MD, Assistant Professor, and Daniel Stulberg, MD, FAAFP, Professor and Chair, Department of Family and Community Medicine, Western Michigan University, Homer Stryker, MD School of Medicine, Kalamazoo.

SAN DIEGO – A split dose of methotrexate (MTX) given orally once per week showed significantly higher efficacy in patients with rheumatoid arthritis at 16 weeks, compared with a single MTX dose weekly, according to new research. By 24 weeks, efficacy measures were similar for both groups.

However, fewer patients in the split-dose group needed additional disease-modifying antirheumatic drugs (DMARDs) to control disease activity.

MTX is a highly utilized, inexpensive drug for RA, but only about 30% of patients can achieve low disease activity or remission on MTX monotherapy, said Varun Dhir, MD, MBBS, of the Postgraduate Institute of Medical Education and Research, Chandigarh, India. He co-authored and presented the research at the annual meeting of the American College of Rheumatology.

Part of the problem is that “oral methotrexate absorption from the gut reduces as the doses go up,” Dr. Dhir noted, because the transport mechanism gets saturated. MTX delivered subcutaneously is one way to improve efficacy, but patients can be needle-averse, and in some countries, like India, pre-filled syringes are not available, he said.

There is pharmacokinetic data dating back 20 years that suggest split-dose MTX could be more efficacious. “However, there are no randomized controlled trials to date, and the guidelines therefore are silent on this approach,” Dr. Dhir said.

To address this question, Dr. Dhir and colleagues recruited patients with RA from six centers across India. Patients were aged 18-60 years, seropositive (rheumatoid factor or anti-citrullinated protein antibodies), and had a disease duration of 5 years or fewer. Patients had active disease, defined as at least four tender joints and at least two swollen joints, and were not taking any DMARDs except for hydroxychloroquine and/or low-dose prednisolone.

A total of 253 patients were randomly assigned to a single 25-mg dose or a split-dose of MTX once weekly (10 mg in the morning and 15 mg in the evening on the same day). The primary outcome was a European Alliance of Associations for Rheumatology (EULAR) good response at 24 weeks. At the 16-week mark, if patients had not achieved low disease activity based on a 28-joint Disease Activity Score (DAS28) greater than 3.2, a blinded assessor could add either leflunomide or sulfasalazine to the continued MTX therapy.

At baseline, there was no difference between the groups’ DAS28, but after 16 weeks, DAS28 was significantly lower in the split-dose group, compared with the single-dose group (4.4 vs. 5.1; P < .001), and a higher percentage of patients in the split-dose group had a EULAR good response.

About three-quarters (76.6%) of patients in the split-dose group experienced an improvement of at least 20% in ACR response criteria (ACR20), compared with 52% in the single-dose group. The split-dose group also had higher proportion of patients achieving ACR50 and ACR70.

About one-third of the split-dose group (35%) added an additional DMARD at 16 weeks, compared with 54.5% of the single-dose group (P = .005).

After 24 weeks, DAS28 scores remained lower in the split-dose group (4.1 vs. 4.5; P = .03), but there were no other differences in treatment responses. Health Assessment Questionnaire scores were the same between both groups at 16 and 24 weeks.

The primary outcome was not met, although Dr. Dhir noted a flaw in the study design that could have affected the results. By allowing patients to add additional DMARDs at 16 weeks, “there were two factors which were affecting the primary outcome” at 24 weeks, he told this news organization. “I feel there was a robust result at least at 16 weeks.”

While there were no major adverse events, the split-dose group had higher rates of transaminitis (elevated liver enzymes) during the study, and low white blood cell count was higher in the single-dose group at 24 weeks. There was no difference in MTX intolerance between the two groups.

“It looks like [the split-dose group] gets out of the block faster. It’s a faster effect,” although the other group did catch up, Janet Pope, MD, MPH, of Western University, London, Ont., said in an interview. She was not involved with the research. Two positive results were the earlier ACR responses in the split-dose group as well as fewer patients in that same group needing to add another DMARD to therapy.

“In my opinion, if it’s equal cost, why not try it and see?” she said.

In a separate presentation referring to the abstract, Joan Bathon, MD, director of rheumatology at Columbia University, New York City, noted that these results align with ACR 2021 recommendations. Dr. Bathon was not involved with this study but was on the writing committee establishing those 2021 guidelines.

“The recommendation – with low certainty of evidence – was that for patients who are intolerant to MTX, that split-dose of oral MTX is worth trying before you switch to a different DMARD,” she said. “I think these data support that concept.”

Dr. Dhir and Dr. Bathon had no relevant financial relationships. Dr. Pope disclosed financial relationships with AbbVie/Abbott, Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Fresenius Kabi, GlaxoSmithKline, Janssen, Mallinckrodt, Novartis, Organon, Pfizer, Sandoz, and Viatris.

A version of this article first appeared on Medscape.com.

SAN DIEGO – A split dose of methotrexate (MTX) given orally once per week showed significantly higher efficacy in patients with rheumatoid arthritis at 16 weeks, compared with a single MTX dose weekly, according to new research. By 24 weeks, efficacy measures were similar for both groups.

However, fewer patients in the split-dose group needed additional disease-modifying antirheumatic drugs (DMARDs) to control disease activity.

MTX is a highly utilized, inexpensive drug for RA, but only about 30% of patients can achieve low disease activity or remission on MTX monotherapy, said Varun Dhir, MD, MBBS, of the Postgraduate Institute of Medical Education and Research, Chandigarh, India. He co-authored and presented the research at the annual meeting of the American College of Rheumatology.

Part of the problem is that “oral methotrexate absorption from the gut reduces as the doses go up,” Dr. Dhir noted, because the transport mechanism gets saturated. MTX delivered subcutaneously is one way to improve efficacy, but patients can be needle-averse, and in some countries, like India, pre-filled syringes are not available, he said.

There is pharmacokinetic data dating back 20 years that suggest split-dose MTX could be more efficacious. “However, there are no randomized controlled trials to date, and the guidelines therefore are silent on this approach,” Dr. Dhir said.

To address this question, Dr. Dhir and colleagues recruited patients with RA from six centers across India. Patients were aged 18-60 years, seropositive (rheumatoid factor or anti-citrullinated protein antibodies), and had a disease duration of 5 years or fewer. Patients had active disease, defined as at least four tender joints and at least two swollen joints, and were not taking any DMARDs except for hydroxychloroquine and/or low-dose prednisolone.

A total of 253 patients were randomly assigned to a single 25-mg dose or a split-dose of MTX once weekly (10 mg in the morning and 15 mg in the evening on the same day). The primary outcome was a European Alliance of Associations for Rheumatology (EULAR) good response at 24 weeks. At the 16-week mark, if patients had not achieved low disease activity based on a 28-joint Disease Activity Score (DAS28) greater than 3.2, a blinded assessor could add either leflunomide or sulfasalazine to the continued MTX therapy.

At baseline, there was no difference between the groups’ DAS28, but after 16 weeks, DAS28 was significantly lower in the split-dose group, compared with the single-dose group (4.4 vs. 5.1; P < .001), and a higher percentage of patients in the split-dose group had a EULAR good response.

About three-quarters (76.6%) of patients in the split-dose group experienced an improvement of at least 20% in ACR response criteria (ACR20), compared with 52% in the single-dose group. The split-dose group also had higher proportion of patients achieving ACR50 and ACR70.

About one-third of the split-dose group (35%) added an additional DMARD at 16 weeks, compared with 54.5% of the single-dose group (P = .005).

After 24 weeks, DAS28 scores remained lower in the split-dose group (4.1 vs. 4.5; P = .03), but there were no other differences in treatment responses. Health Assessment Questionnaire scores were the same between both groups at 16 and 24 weeks.

The primary outcome was not met, although Dr. Dhir noted a flaw in the study design that could have affected the results. By allowing patients to add additional DMARDs at 16 weeks, “there were two factors which were affecting the primary outcome” at 24 weeks, he told this news organization. “I feel there was a robust result at least at 16 weeks.”

While there were no major adverse events, the split-dose group had higher rates of transaminitis (elevated liver enzymes) during the study, and low white blood cell count was higher in the single-dose group at 24 weeks. There was no difference in MTX intolerance between the two groups.

“It looks like [the split-dose group] gets out of the block faster. It’s a faster effect,” although the other group did catch up, Janet Pope, MD, MPH, of Western University, London, Ont., said in an interview. She was not involved with the research. Two positive results were the earlier ACR responses in the split-dose group as well as fewer patients in that same group needing to add another DMARD to therapy.

“In my opinion, if it’s equal cost, why not try it and see?” she said.

In a separate presentation referring to the abstract, Joan Bathon, MD, director of rheumatology at Columbia University, New York City, noted that these results align with ACR 2021 recommendations. Dr. Bathon was not involved with this study but was on the writing committee establishing those 2021 guidelines.

“The recommendation – with low certainty of evidence – was that for patients who are intolerant to MTX, that split-dose of oral MTX is worth trying before you switch to a different DMARD,” she said. “I think these data support that concept.”

Dr. Dhir and Dr. Bathon had no relevant financial relationships. Dr. Pope disclosed financial relationships with AbbVie/Abbott, Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Fresenius Kabi, GlaxoSmithKline, Janssen, Mallinckrodt, Novartis, Organon, Pfizer, Sandoz, and Viatris.

A version of this article first appeared on Medscape.com.

SAN DIEGO – A split dose of methotrexate (MTX) given orally once per week showed significantly higher efficacy in patients with rheumatoid arthritis at 16 weeks, compared with a single MTX dose weekly, according to new research. By 24 weeks, efficacy measures were similar for both groups.

However, fewer patients in the split-dose group needed additional disease-modifying antirheumatic drugs (DMARDs) to control disease activity.

MTX is a highly utilized, inexpensive drug for RA, but only about 30% of patients can achieve low disease activity or remission on MTX monotherapy, said Varun Dhir, MD, MBBS, of the Postgraduate Institute of Medical Education and Research, Chandigarh, India. He co-authored and presented the research at the annual meeting of the American College of Rheumatology.

Part of the problem is that “oral methotrexate absorption from the gut reduces as the doses go up,” Dr. Dhir noted, because the transport mechanism gets saturated. MTX delivered subcutaneously is one way to improve efficacy, but patients can be needle-averse, and in some countries, like India, pre-filled syringes are not available, he said.

There is pharmacokinetic data dating back 20 years that suggest split-dose MTX could be more efficacious. “However, there are no randomized controlled trials to date, and the guidelines therefore are silent on this approach,” Dr. Dhir said.

To address this question, Dr. Dhir and colleagues recruited patients with RA from six centers across India. Patients were aged 18-60 years, seropositive (rheumatoid factor or anti-citrullinated protein antibodies), and had a disease duration of 5 years or fewer. Patients had active disease, defined as at least four tender joints and at least two swollen joints, and were not taking any DMARDs except for hydroxychloroquine and/or low-dose prednisolone.

A total of 253 patients were randomly assigned to a single 25-mg dose or a split-dose of MTX once weekly (10 mg in the morning and 15 mg in the evening on the same day). The primary outcome was a European Alliance of Associations for Rheumatology (EULAR) good response at 24 weeks. At the 16-week mark, if patients had not achieved low disease activity based on a 28-joint Disease Activity Score (DAS28) greater than 3.2, a blinded assessor could add either leflunomide or sulfasalazine to the continued MTX therapy.

At baseline, there was no difference between the groups’ DAS28, but after 16 weeks, DAS28 was significantly lower in the split-dose group, compared with the single-dose group (4.4 vs. 5.1; P < .001), and a higher percentage of patients in the split-dose group had a EULAR good response.

About three-quarters (76.6%) of patients in the split-dose group experienced an improvement of at least 20% in ACR response criteria (ACR20), compared with 52% in the single-dose group. The split-dose group also had higher proportion of patients achieving ACR50 and ACR70.

About one-third of the split-dose group (35%) added an additional DMARD at 16 weeks, compared with 54.5% of the single-dose group (P = .005).

After 24 weeks, DAS28 scores remained lower in the split-dose group (4.1 vs. 4.5; P = .03), but there were no other differences in treatment responses. Health Assessment Questionnaire scores were the same between both groups at 16 and 24 weeks.

The primary outcome was not met, although Dr. Dhir noted a flaw in the study design that could have affected the results. By allowing patients to add additional DMARDs at 16 weeks, “there were two factors which were affecting the primary outcome” at 24 weeks, he told this news organization. “I feel there was a robust result at least at 16 weeks.”

While there were no major adverse events, the split-dose group had higher rates of transaminitis (elevated liver enzymes) during the study, and low white blood cell count was higher in the single-dose group at 24 weeks. There was no difference in MTX intolerance between the two groups.

“It looks like [the split-dose group] gets out of the block faster. It’s a faster effect,” although the other group did catch up, Janet Pope, MD, MPH, of Western University, London, Ont., said in an interview. She was not involved with the research. Two positive results were the earlier ACR responses in the split-dose group as well as fewer patients in that same group needing to add another DMARD to therapy.

“In my opinion, if it’s equal cost, why not try it and see?” she said.

In a separate presentation referring to the abstract, Joan Bathon, MD, director of rheumatology at Columbia University, New York City, noted that these results align with ACR 2021 recommendations. Dr. Bathon was not involved with this study but was on the writing committee establishing those 2021 guidelines.

“The recommendation – with low certainty of evidence – was that for patients who are intolerant to MTX, that split-dose of oral MTX is worth trying before you switch to a different DMARD,” she said. “I think these data support that concept.”

Dr. Dhir and Dr. Bathon had no relevant financial relationships. Dr. Pope disclosed financial relationships with AbbVie/Abbott, Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Fresenius Kabi, GlaxoSmithKline, Janssen, Mallinckrodt, Novartis, Organon, Pfizer, Sandoz, and Viatris.

A version of this article first appeared on Medscape.com.

The European Commission has approved lebrikizumab for the treatment of moderate-to-severe atopic dermatitis (AD) in patients aged 12 years and older who have failed topical therapies, according to a press release from the manufacturer.

Lebrikizumab, which selectively targets interleukin-13 and inhibits its signaling pathway, will first be available in Germany, with a rollout in other European countries expected through 2024, according to Almirall, the manufacturer.

The European approval of lebrikizumab (Ebglyss) was based on data from a trio of pivotal phase 3 studies including ADvocate1 and ADvocate2, which evaluated lebrikizumab as monotherapy, and ADhere, which evaluated lebrikizumab in combination with topical corticosteroids. All three trials included adult and adolescent patients aged 12 years and older with moderate-to-severe AD.

In the two ADvocate studies, published in the New England Journal of Medicine, participants were randomized to a 250-mg injection of lebrikizumab or placebo every 2 weeks. The primary outcome was a score of clear or almost clear skin based on the Investigator’s Global Assessment with at least a 2-point reduction from baseline to 16 weeks. 

Compared with placebo, lebrikizumab showed significant clinical efficacy in both studies. In study 1, 43.1% of 283 patients treated with lebrikizumab versus 12.7% of 141 patients on placebo met the primary endpoint (P < .001), as did 33.2% of the 281 patients on lebrikizumab and 10.8% of 146 patients on placebo in study 2 (P < .001). In addition, 58.8% and 52.1% of patients on lebrikizumab in studies 1 and 2, respectively, met the secondary endpoint of a 75% reduction in the Eczema Area and Severity Index score (EASI-75), versus 16.2% and 18.1% of patients on placebo in study 1 and 2, respectively (P < .001 for both).

In the ADhere study, published in JAMA Dermatology, 41.2% of patients receiving a lebrikizumab/corticosteroid combination and 22.1% of those randomized to a placebo/corticosteroid combination met the primary endpoint of IGA scores of 0 or 1 at 16 weeks, and nearly 70% patients treated with a combination of lebrikizumab and topical corticosteroids achieved EASI-75, compared with 42% of those on the combination.

Nearly 80% of patients who responded at 16 weeks and continued treatment with lebrikizumab as monotherapy or combination therapy showed sustained results up to 52 weeks with maintenance monthly dosing, according to the Almirall press release.

Most adverse events across the studies were mild or moderate and were not associated with treatment discontinuation. The most common adverse reactions were conjunctivitis, injection site reactions, allergic conjunctivitis, and dry eye.

Further research has shown showed clinical efficacy and safety in patients who used lebrikizumab for up to 2 years, either as monotherapy or in combination with topical corticosteroids, according to the manufacturer.

Lebrikizumab remains under review in the United States after the Food and Drug Administration issued a complete response letter in October regarding findings made during an inspection of a third-party contract manufacturer that included the “monoclonal antibody drug substance” for lebrikizumab, although no concerns about clinical data or safety were raised, Eli Lilly announced in October. Eli Lilly has the rights to develop lebrikizumab in the United States and the rest of the world excluding Europe.

The European Commission has approved lebrikizumab for the treatment of moderate-to-severe atopic dermatitis (AD) in patients aged 12 years and older who have failed topical therapies, according to a press release from the manufacturer.

Lebrikizumab, which selectively targets interleukin-13 and inhibits its signaling pathway, will first be available in Germany, with a rollout in other European countries expected through 2024, according to Almirall, the manufacturer.

The European approval of lebrikizumab (Ebglyss) was based on data from a trio of pivotal phase 3 studies including ADvocate1 and ADvocate2, which evaluated lebrikizumab as monotherapy, and ADhere, which evaluated lebrikizumab in combination with topical corticosteroids. All three trials included adult and adolescent patients aged 12 years and older with moderate-to-severe AD.

In the two ADvocate studies, published in the New England Journal of Medicine, participants were randomized to a 250-mg injection of lebrikizumab or placebo every 2 weeks. The primary outcome was a score of clear or almost clear skin based on the Investigator’s Global Assessment with at least a 2-point reduction from baseline to 16 weeks. 

Compared with placebo, lebrikizumab showed significant clinical efficacy in both studies. In study 1, 43.1% of 283 patients treated with lebrikizumab versus 12.7% of 141 patients on placebo met the primary endpoint (P < .001), as did 33.2% of the 281 patients on lebrikizumab and 10.8% of 146 patients on placebo in study 2 (P < .001). In addition, 58.8% and 52.1% of patients on lebrikizumab in studies 1 and 2, respectively, met the secondary endpoint of a 75% reduction in the Eczema Area and Severity Index score (EASI-75), versus 16.2% and 18.1% of patients on placebo in study 1 and 2, respectively (P < .001 for both).

In the ADhere study, published in JAMA Dermatology, 41.2% of patients receiving a lebrikizumab/corticosteroid combination and 22.1% of those randomized to a placebo/corticosteroid combination met the primary endpoint of IGA scores of 0 or 1 at 16 weeks, and nearly 70% patients treated with a combination of lebrikizumab and topical corticosteroids achieved EASI-75, compared with 42% of those on the combination.

Nearly 80% of patients who responded at 16 weeks and continued treatment with lebrikizumab as monotherapy or combination therapy showed sustained results up to 52 weeks with maintenance monthly dosing, according to the Almirall press release.

Most adverse events across the studies were mild or moderate and were not associated with treatment discontinuation. The most common adverse reactions were conjunctivitis, injection site reactions, allergic conjunctivitis, and dry eye.

Further research has shown showed clinical efficacy and safety in patients who used lebrikizumab for up to 2 years, either as monotherapy or in combination with topical corticosteroids, according to the manufacturer.

Lebrikizumab remains under review in the United States after the Food and Drug Administration issued a complete response letter in October regarding findings made during an inspection of a third-party contract manufacturer that included the “monoclonal antibody drug substance” for lebrikizumab, although no concerns about clinical data or safety were raised, Eli Lilly announced in October. Eli Lilly has the rights to develop lebrikizumab in the United States and the rest of the world excluding Europe.

The European Commission has approved lebrikizumab for the treatment of moderate-to-severe atopic dermatitis (AD) in patients aged 12 years and older who have failed topical therapies, according to a press release from the manufacturer.

Lebrikizumab, which selectively targets interleukin-13 and inhibits its signaling pathway, will first be available in Germany, with a rollout in other European countries expected through 2024, according to Almirall, the manufacturer.

The European approval of lebrikizumab (Ebglyss) was based on data from a trio of pivotal phase 3 studies including ADvocate1 and ADvocate2, which evaluated lebrikizumab as monotherapy, and ADhere, which evaluated lebrikizumab in combination with topical corticosteroids. All three trials included adult and adolescent patients aged 12 years and older with moderate-to-severe AD.

In the two ADvocate studies, published in the New England Journal of Medicine, participants were randomized to a 250-mg injection of lebrikizumab or placebo every 2 weeks. The primary outcome was a score of clear or almost clear skin based on the Investigator’s Global Assessment with at least a 2-point reduction from baseline to 16 weeks. 

Compared with placebo, lebrikizumab showed significant clinical efficacy in both studies. In study 1, 43.1% of 283 patients treated with lebrikizumab versus 12.7% of 141 patients on placebo met the primary endpoint (P < .001), as did 33.2% of the 281 patients on lebrikizumab and 10.8% of 146 patients on placebo in study 2 (P < .001). In addition, 58.8% and 52.1% of patients on lebrikizumab in studies 1 and 2, respectively, met the secondary endpoint of a 75% reduction in the Eczema Area and Severity Index score (EASI-75), versus 16.2% and 18.1% of patients on placebo in study 1 and 2, respectively (P < .001 for both).

In the ADhere study, published in JAMA Dermatology, 41.2% of patients receiving a lebrikizumab/corticosteroid combination and 22.1% of those randomized to a placebo/corticosteroid combination met the primary endpoint of IGA scores of 0 or 1 at 16 weeks, and nearly 70% patients treated with a combination of lebrikizumab and topical corticosteroids achieved EASI-75, compared with 42% of those on the combination.

Nearly 80% of patients who responded at 16 weeks and continued treatment with lebrikizumab as monotherapy or combination therapy showed sustained results up to 52 weeks with maintenance monthly dosing, according to the Almirall press release.

Most adverse events across the studies were mild or moderate and were not associated with treatment discontinuation. The most common adverse reactions were conjunctivitis, injection site reactions, allergic conjunctivitis, and dry eye.

Further research has shown showed clinical efficacy and safety in patients who used lebrikizumab for up to 2 years, either as monotherapy or in combination with topical corticosteroids, according to the manufacturer.

Lebrikizumab remains under review in the United States after the Food and Drug Administration issued a complete response letter in October regarding findings made during an inspection of a third-party contract manufacturer that included the “monoclonal antibody drug substance” for lebrikizumab, although no concerns about clinical data or safety were raised, Eli Lilly announced in October. Eli Lilly has the rights to develop lebrikizumab in the United States and the rest of the world excluding Europe.

TOPLINE:

Overall, making comprehensive dietary changes in line with a Mediterranean diet did not reduce women’s risk for breast cancer recurrence or metastasis. However, women at high risk for recurrence who made the greatest improvements in their diet quality demonstrated a 41% lower risk for recurrence, compared with peers who made the fewest improvements.

METHODOLOGY:

• A growing body of evidence suggests that a better dietary quality may improve survival among patients with breast cancer, but whether diet impacts breast cancer–specific mortality remains controversial.
• To better understand the relationship between diet and breast cancer outcomes, investigators recruited 1,542 women with breast cancer who had undergone surgical resection in the past 5 years and were considered high risk for recurrence.
• All women received general recommendations for cancer prevention, while the intervention group received active support to adhere to a macro–Mediterranean-style diet, which encourages mainly consuming whole grains, legumes, and high-fiber vegetables and discourages eating foods high in saturated and trans fats, processed meats, and foods and beverages high in sugar.
• Diet was assessed at baseline, 1 year, and every few months in subsequent years via food frequency diaries. Compliance with dietary recommendations for the whole cohort was assessed using a dietary index developed for the trial.
• In addition to diet, women in the diet intervention group were encouraged to maintain moderate to intense physical activity – 30 minutes, on average, each day – and received pedometers to track steps, aiming for 10,000 per day.
•  

TAKEAWAY:

• Over 5 years of follow-up, the rate of breast cancer recurrence did not differ between women in the diet intervention group and those in the control group. Overall, 95 of 769 women in the intervention group and 98 of 773 in the control group had a breast cancer recurrence (hazard ratio, 0.99).
• When evaluating outcomes in the entire cohort, looking at everyone’s level of compliance with dietary recommendations, women who adhered the most to the dietary guidelines had a 41% lower recurrence risk compared with women who adhered the least (HR, 0.59).
• The greatest protective effect among women who demonstrated high compliance occurred in those with ER-positive cancers (HR, 0.42) and those with ER-positive cancers who received tamoxifen (HR, 0.30).
•  

IN PRACTICE:

This intervention trial “did not confirm the hypothesis that a comprehensive dietary modification reduces breast cancer recurrence and metastases,” but when looking at compliance to the Mediterranean diet overall, the analysis did find “a significantly better prognosis” for women with the best adherence.

SOURCE:

The study, with first author Franco Berrino, MD, PhD, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, was published online in Clinical Cancer Research. 

LIMITATIONS:

The study relied on self-reported dietary data. No dietary instrument was used to estimate nutrient intake and the dietary index developed for the trial remains unvalidated.

DISCLOSURES:

The study was supported by the Italian Department of Health, the Associazione Italiana per la Ricerca sul Cancro, and the Vita e Salute Foundation. The authors reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

TOPLINE:

Overall, making comprehensive dietary changes in line with a Mediterranean diet did not reduce women’s risk for breast cancer recurrence or metastasis. However, women at high risk for recurrence who made the greatest improvements in their diet quality demonstrated a 41% lower risk for recurrence, compared with peers who made the fewest improvements.

METHODOLOGY:

• A growing body of evidence suggests that a better dietary quality may improve survival among patients with breast cancer, but whether diet impacts breast cancer–specific mortality remains controversial.
• To better understand the relationship between diet and breast cancer outcomes, investigators recruited 1,542 women with breast cancer who had undergone surgical resection in the past 5 years and were considered high risk for recurrence.
• All women received general recommendations for cancer prevention, while the intervention group received active support to adhere to a macro–Mediterranean-style diet, which encourages mainly consuming whole grains, legumes, and high-fiber vegetables and discourages eating foods high in saturated and trans fats, processed meats, and foods and beverages high in sugar.
• Diet was assessed at baseline, 1 year, and every few months in subsequent years via food frequency diaries. Compliance with dietary recommendations for the whole cohort was assessed using a dietary index developed for the trial.
• In addition to diet, women in the diet intervention group were encouraged to maintain moderate to intense physical activity – 30 minutes, on average, each day – and received pedometers to track steps, aiming for 10,000 per day.
•  

TAKEAWAY:

• Over 5 years of follow-up, the rate of breast cancer recurrence did not differ between women in the diet intervention group and those in the control group. Overall, 95 of 769 women in the intervention group and 98 of 773 in the control group had a breast cancer recurrence (hazard ratio, 0.99).
• When evaluating outcomes in the entire cohort, looking at everyone’s level of compliance with dietary recommendations, women who adhered the most to the dietary guidelines had a 41% lower recurrence risk compared with women who adhered the least (HR, 0.59).
• The greatest protective effect among women who demonstrated high compliance occurred in those with ER-positive cancers (HR, 0.42) and those with ER-positive cancers who received tamoxifen (HR, 0.30).
•  

IN PRACTICE:

This intervention trial “did not confirm the hypothesis that a comprehensive dietary modification reduces breast cancer recurrence and metastases,” but when looking at compliance to the Mediterranean diet overall, the analysis did find “a significantly better prognosis” for women with the best adherence.

SOURCE:

The study, with first author Franco Berrino, MD, PhD, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, was published online in Clinical Cancer Research. 

LIMITATIONS:

The study relied on self-reported dietary data. No dietary instrument was used to estimate nutrient intake and the dietary index developed for the trial remains unvalidated.

DISCLOSURES:

The study was supported by the Italian Department of Health, the Associazione Italiana per la Ricerca sul Cancro, and the Vita e Salute Foundation. The authors reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

TOPLINE:

Overall, making comprehensive dietary changes in line with a Mediterranean diet did not reduce women’s risk for breast cancer recurrence or metastasis. However, women at high risk for recurrence who made the greatest improvements in their diet quality demonstrated a 41% lower risk for recurrence, compared with peers who made the fewest improvements.

METHODOLOGY:

• A growing body of evidence suggests that a better dietary quality may improve survival among patients with breast cancer, but whether diet impacts breast cancer–specific mortality remains controversial.
• To better understand the relationship between diet and breast cancer outcomes, investigators recruited 1,542 women with breast cancer who had undergone surgical resection in the past 5 years and were considered high risk for recurrence.
• All women received general recommendations for cancer prevention, while the intervention group received active support to adhere to a macro–Mediterranean-style diet, which encourages mainly consuming whole grains, legumes, and high-fiber vegetables and discourages eating foods high in saturated and trans fats, processed meats, and foods and beverages high in sugar.
• Diet was assessed at baseline, 1 year, and every few months in subsequent years via food frequency diaries. Compliance with dietary recommendations for the whole cohort was assessed using a dietary index developed for the trial.
• In addition to diet, women in the diet intervention group were encouraged to maintain moderate to intense physical activity – 30 minutes, on average, each day – and received pedometers to track steps, aiming for 10,000 per day.
•  

TAKEAWAY:

• Over 5 years of follow-up, the rate of breast cancer recurrence did not differ between women in the diet intervention group and those in the control group. Overall, 95 of 769 women in the intervention group and 98 of 773 in the control group had a breast cancer recurrence (hazard ratio, 0.99).
• When evaluating outcomes in the entire cohort, looking at everyone’s level of compliance with dietary recommendations, women who adhered the most to the dietary guidelines had a 41% lower recurrence risk compared with women who adhered the least (HR, 0.59).
• The greatest protective effect among women who demonstrated high compliance occurred in those with ER-positive cancers (HR, 0.42) and those with ER-positive cancers who received tamoxifen (HR, 0.30).
•  

IN PRACTICE:

This intervention trial “did not confirm the hypothesis that a comprehensive dietary modification reduces breast cancer recurrence and metastases,” but when looking at compliance to the Mediterranean diet overall, the analysis did find “a significantly better prognosis” for women with the best adherence.

SOURCE:

The study, with first author Franco Berrino, MD, PhD, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, was published online in Clinical Cancer Research. 

LIMITATIONS:

The study relied on self-reported dietary data. No dietary instrument was used to estimate nutrient intake and the dietary index developed for the trial remains unvalidated.

DISCLOSURES:

The study was supported by the Italian Department of Health, the Associazione Italiana per la Ricerca sul Cancro, and the Vita e Salute Foundation. The authors reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The Food and Drug Administration has approved capivasertib (Truqap, AstraZeneca Pharmaceuticals) with fulvestrant for certain previously treated adults with hormone receptor (HR)–positive, human epidermal growth factor receptor (HER2)–negative, locally advanced or metastatic breast cancer.

Specifically, the first-in-class AKT kinase inhibitor approval is for patients with one or more PIK3CA/AKT1/PTEN alterations, as detected by an FDA-approved test, whose metastatic disease progressed on at least one endocrine-based regimen or who experienced recurrence on or within 12 months of completing adjuvant therapy, according to the FDA approval announcement.

Olivier Le Moal/Getty Images

The FDA also approved a companion diagnostic device, the FoundationOne CDx assay, to identify patients who are eligible for treatment with capivasertib.

Approval of capivasertib was based on findings from the randomized, placebo-controlled, phase 3 CAPItello-291 trial, which involved 708 patients with locally advanced or metastatic HR-positive, HER2-negative breast cancer, including 289 whose tumors had PIK3CA/AKT1/PTEN alterations. All had progressed on aromatase inhibitor–based treatment and may have received up to two prior lines of endocrine therapy and up to one line of chemotherapy.

Patients were randomized to either 400 mg of oral capivasertib or placebo twice daily for 4 days, followed by 3 days off treatment each week over a 28-day treatment cycle. Patients in both arms received 500 mg intramuscular fulvestrant on cycle 1 days 1 and 15, and then every 28 days thereafter. Treatment continued until disease progression or unacceptable toxicity.

In the 289 patients with PIK3CA/AKT1/PTEN–altered tumors, median progression-free survival (PFS) in the capivasertib arm was 7.3 months versus 3.1 months in the placebo group (hazard ratio, 0.50).

An exploratory analysis of PFS in the 313 (44%) patients whose tumors did not have a PIK3CA/AKT1/PTEN alteration demonstrated a less notable benefit to the combination (HR, 0.79; 95% confidence interval, 0.61-1.02), indicating that “the difference in the overall population was primarily attributed to the results seen in the population of patients whose tumors have PIK3CA/AKT1/PTEN alteration,” the FDA explained.

Adverse reactions occurring in at least 20% of patients included decreased lymphocytes, leukocytes, hemoglobin, and neutrophils; increased fasting glucose, creatinine, and triglycerides; and diarrhea, nausea, fatigue, vomiting, and stomatitis.

The recommended capivasertib dose is 400 mg orally twice daily, given about 12 hours apart with or without food, for 4 days followed by 3 off days until disease progression or unacceptable toxicity, according to the prescribing information.

A version of this article first appeared on Medscape.com.

The Food and Drug Administration has approved capivasertib (Truqap, AstraZeneca Pharmaceuticals) with fulvestrant for certain previously treated adults with hormone receptor (HR)–positive, human epidermal growth factor receptor (HER2)–negative, locally advanced or metastatic breast cancer.

Specifically, the first-in-class AKT kinase inhibitor approval is for patients with one or more PIK3CA/AKT1/PTEN alterations, as detected by an FDA-approved test, whose metastatic disease progressed on at least one endocrine-based regimen or who experienced recurrence on or within 12 months of completing adjuvant therapy, according to the FDA approval announcement.

Olivier Le Moal/Getty Images

The FDA also approved a companion diagnostic device, the FoundationOne CDx assay, to identify patients who are eligible for treatment with capivasertib.

Approval of capivasertib was based on findings from the randomized, placebo-controlled, phase 3 CAPItello-291 trial, which involved 708 patients with locally advanced or metastatic HR-positive, HER2-negative breast cancer, including 289 whose tumors had PIK3CA/AKT1/PTEN alterations. All had progressed on aromatase inhibitor–based treatment and may have received up to two prior lines of endocrine therapy and up to one line of chemotherapy.

Patients were randomized to either 400 mg of oral capivasertib or placebo twice daily for 4 days, followed by 3 days off treatment each week over a 28-day treatment cycle. Patients in both arms received 500 mg intramuscular fulvestrant on cycle 1 days 1 and 15, and then every 28 days thereafter. Treatment continued until disease progression or unacceptable toxicity.

In the 289 patients with PIK3CA/AKT1/PTEN–altered tumors, median progression-free survival (PFS) in the capivasertib arm was 7.3 months versus 3.1 months in the placebo group (hazard ratio, 0.50).

An exploratory analysis of PFS in the 313 (44%) patients whose tumors did not have a PIK3CA/AKT1/PTEN alteration demonstrated a less notable benefit to the combination (HR, 0.79; 95% confidence interval, 0.61-1.02), indicating that “the difference in the overall population was primarily attributed to the results seen in the population of patients whose tumors have PIK3CA/AKT1/PTEN alteration,” the FDA explained.

Adverse reactions occurring in at least 20% of patients included decreased lymphocytes, leukocytes, hemoglobin, and neutrophils; increased fasting glucose, creatinine, and triglycerides; and diarrhea, nausea, fatigue, vomiting, and stomatitis.

The recommended capivasertib dose is 400 mg orally twice daily, given about 12 hours apart with or without food, for 4 days followed by 3 off days until disease progression or unacceptable toxicity, according to the prescribing information.

A version of this article first appeared on Medscape.com.

The Food and Drug Administration has approved capivasertib (Truqap, AstraZeneca Pharmaceuticals) with fulvestrant for certain previously treated adults with hormone receptor (HR)–positive, human epidermal growth factor receptor (HER2)–negative, locally advanced or metastatic breast cancer.

Specifically, the first-in-class AKT kinase inhibitor approval is for patients with one or more PIK3CA/AKT1/PTEN alterations, as detected by an FDA-approved test, whose metastatic disease progressed on at least one endocrine-based regimen or who experienced recurrence on or within 12 months of completing adjuvant therapy, according to the FDA approval announcement.

Olivier Le Moal/Getty Images

The FDA also approved a companion diagnostic device, the FoundationOne CDx assay, to identify patients who are eligible for treatment with capivasertib.

Approval of capivasertib was based on findings from the randomized, placebo-controlled, phase 3 CAPItello-291 trial, which involved 708 patients with locally advanced or metastatic HR-positive, HER2-negative breast cancer, including 289 whose tumors had PIK3CA/AKT1/PTEN alterations. All had progressed on aromatase inhibitor–based treatment and may have received up to two prior lines of endocrine therapy and up to one line of chemotherapy.

Patients were randomized to either 400 mg of oral capivasertib or placebo twice daily for 4 days, followed by 3 days off treatment each week over a 28-day treatment cycle. Patients in both arms received 500 mg intramuscular fulvestrant on cycle 1 days 1 and 15, and then every 28 days thereafter. Treatment continued until disease progression or unacceptable toxicity.

In the 289 patients with PIK3CA/AKT1/PTEN–altered tumors, median progression-free survival (PFS) in the capivasertib arm was 7.3 months versus 3.1 months in the placebo group (hazard ratio, 0.50).

An exploratory analysis of PFS in the 313 (44%) patients whose tumors did not have a PIK3CA/AKT1/PTEN alteration demonstrated a less notable benefit to the combination (HR, 0.79; 95% confidence interval, 0.61-1.02), indicating that “the difference in the overall population was primarily attributed to the results seen in the population of patients whose tumors have PIK3CA/AKT1/PTEN alteration,” the FDA explained.

Adverse reactions occurring in at least 20% of patients included decreased lymphocytes, leukocytes, hemoglobin, and neutrophils; increased fasting glucose, creatinine, and triglycerides; and diarrhea, nausea, fatigue, vomiting, and stomatitis.

The recommended capivasertib dose is 400 mg orally twice daily, given about 12 hours apart with or without food, for 4 days followed by 3 off days until disease progression or unacceptable toxicity, according to the prescribing information.

A version of this article first appeared on Medscape.com.

Money talks.

The United States faces a serious shortage of primary care physicians for many reasons, but one, in particular, is inescapable: compensation.

Substantial disparities between what primary care physicians earn relative to specialists like orthopedists and cardiologists can weigh into medical students’ decisions about which field to choose. Plus, the system that Medicare and other health plans use to pay doctors generally places more value on doing procedures like replacing a knee or inserting a stent than on delivering the whole-person, long-term health care management that primary care physicians provide.

As a result of those pay disparities, and the punishing workload typically faced by primary care physicians, more new doctors are becoming specialists, often leaving patients with fewer choices for primary care.

“There is a public out there that is dissatisfied with the lack of access to a routine source of care,” said Christopher Koller, president of the Milbank Memorial Fund, a foundation that focuses on improving population health and health equity. “That’s not going to be addressed until we pay for it.”

Primary care is the foundation of our health care system, the only area in which providing more services – such as childhood vaccines and regular blood pressure screenings – is linked to better population health and more equitable outcomes, according to the National Academies of Sciences, Engineering, and Medicine, in a recently published report on how to rebuild primary care. Without it, the national academies wrote, “minor health problems can spiral into chronic disease,” with poor disease management, ED overuse, and unsustainable costs. Yet for decades, the United States has underinvested in primary care. It accounted for less than 5% of health care spending in 2020 – significantly less than the average spending by countries that are members of the Organization for Economic Cooperation and Development, according to the report.

A $26 billion piece of bipartisan legislation proposed last month by Sen. Bernie Sanders (I-Vt.), chair of the Senate Health, Education, Labor, and Pensions Committee, and Sen. Roger Marshall (R-Kan.) would bolster primary care by increasing training opportunities for doctors and nurses and expanding access to community health centers. Policy experts say the bill would provide important support, but it’s not enough. It doesn’t touch compensation.

“We need primary care to be paid differently and to be paid more, and that starts with Medicare,” Mr. Koller said.
 

How Medicare drives payment

Medicare, which covers 65 million people who are 65 and older or who have certain long-term disabilities, finances more than a fifth of all health care spending — giving it significant muscle in the health care market. Private health plans typically base their payment amounts on the Medicare system, so what Medicare pays is crucial.

Under the Medicare payment system, the amount the program pays for a medical service is determined by three geographically weighted components: a physician’s work, including time and intensity; the practice’s expense, such as overhead and equipment; and professional insurance. It tends to reward specialties that emphasize procedures, such as repairing a hernia or removing a tumor, more than primary care, where the focus is on talking with patients, answering questions, and educating them about managing their chronic conditions.

Medical students may not be familiar with the particulars of how the payment system works, but their clinical training exposes them to a punishing workload and burnout that is contributing to the shortage of primary care physicians, projected to reach up to 48,000 by 2034, according to estimates from the Association of American Medical Colleges.

The earnings differential between primary care and other specialists is also not lost on them. Average annual compensation for doctors who focus on primary care – family medicine, internists, and pediatricians – ranges from an average of about $250,000 to $275,000, according to Medscape’s annual physician compensation report. Many specialists make more than twice as much: Plastic surgeons top the compensation list at $619,000 annually, followed by orthopedists ($573,000) and cardiologists ($507,000).

“I think the major issues in terms of the primary care physician pipeline are the compensation and the work of primary care,” said Russ Phillips, MD, an internist and the director of the Harvard Medical School Center for Primary Care, Boston. “You have to really want to be a primary care physician when that student will make one-third of what students going into dermatology will make.”

According to statistics from the National Resident Matching Program, which tracks the number of residency slots available for graduating medical students and the number of slots filled, 89% of 5,088 family medicine residency slots were filled in 2023, compared with a 93% residency fill rate overall. Internists had a higher fill rate, 96%, but a significant proportion of internal medicine residents eventually practice in a specialty area rather than in primary care.

No one would claim that doctors are poorly paid, but with the average medical student graduating with just over $200,000 in medical school debt, making a good salary matters.
 

Not in it for the money

Still, it’s a misperception that student debt always drives the decision whether to go into primary care, said Len Marquez, senior director of government relations and legislative advocacy at the Association of American Medical Colleges.

For Anitza Quintero, 24, a second-year medical student at the Geisinger Commonwealth School of Medicine in rural Pennsylvania, primary care is a logical extension of her interest in helping children and immigrants. Ms. Quintero’s family came to the United States on a raft from Cuba before she was born. She plans to focus on internal medicine and pediatrics.

“I want to keep going to help my family and other families,” Ms. Quintero said. “There’s obviously something attractive about having a specialty and a high pay grade,” Still, she wants to work “where the whole body is involved,” she said, adding that long-term doctor-patient relationships are “also attractive.”

Ms. Quintero is part of the Abigail Geisinger Scholars Program, which aims to recruit primary care physicians and psychiatrists to the rural health system in part with a promise of medical school loan forgiveness. Health care shortages tend to be more acute in rural areas.

These students’ education costs are covered, and they receive a $2,000 monthly stipend. They can do their residency elsewhere, but upon completing it they return to Geisinger for a primary care job with the health care system. Every year of work there erases one year of the debt covered by their award. If they don’t take a job with the health care system, they must repay the amount they received.
 

Payment imbalances a source of tension

In recent years, the Centers for Medicare & Medicaid Services, which administers the Medicare program, has made changes to address some of the payment imbalances between primary care and specialist services. The agency has expanded the office visit services for which providers can bill to manage their patients, including adding nonprocedural billing codes for providing transitional care, chronic care management, and advance care planning.

In 2024’s final physician fee schedule, the agency plans to allow another new code to take effect, G2211. It would let physicians bill for complex patient evaluation and management services. Any physician could use the code, but it is expected that primary care physicians would use it more frequently than specialists. Congress has delayed implementation of the code since 2021.

The new code is a tiny piece of overall payment reform, “but it is critically important, and it is our top priority on the Hill right now,” said Shari Erickson, chief advocacy officer for the American College of Physicians.

It also triggered a tussle that highlights ongoing tension in Medicare physician payment rules.

The American College of Surgeons and 18 other specialty groups published a statement describing the new code as “unnecessary.” They oppose its implementation because it would primarily benefit primary care providers who, they say, already have the flexibility to bill more for more complex visits.

But the real issue is that, under federal law, changes to Medicare physician payments must preserve budget neutrality, a zero-sum arrangement in which payment increases for primary care providers mean payment decreases elsewhere.

“If they want to keep it, they need to pay for it,” said Christian Shalgian, director of the division of advocacy and health policy for the American College of Surgeons, noting that his organization will continue to oppose implementation otherwise.

Still, there’s general agreement that strengthening the primary care system through payment reform won’t be accomplished by tinkering with billing codes.

The current fee-for-service system doesn’t fully accommodate the time and effort primary care physicians put into “small-ticket” activities like emails and phone calls, reviews of lab results, and consultation reports. A better arrangement, they say, would be to pay primary care physicians a set monthly amount per patient to provide all their care, a system called capitation.

“We’re much better off paying on a per capita basis, get that monthly payment paid in advance plus some extra amount for other things,” said Paul Ginsburg, PhD, a senior fellow at the University of Southern California Schaeffer Center for Health Policy and Economics and former commissioner of the Medicare Payment Advisory Commission.

But if adding a single five-character code to Medicare’s payment rules has proved challenging, imagine the heavy lift involved in overhauling the program’s entire physician payment system. MedPAC and the national academies, both of which provide advice to Congress, have weighed in on the broad outlines of what such a transformation might look like. And there are targeted efforts in Congress: For instance, a bill that would add an annual inflation update to Medicare physician payments and a proposal to address budget neutrality. But it’s unclear whether lawmakers have strong interest in taking action.

“The fact that Medicare has been squeezing physician payment rates for 2 decades is making reforming their structure more difficult,” said Dr. Ginsburg. “The losers are more sensitive to reductions in the rates for the procedures they do.”

KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF—an independent source of health policy research, polling, and journalism. Learn more about KFF.

Money talks.

The United States faces a serious shortage of primary care physicians for many reasons, but one, in particular, is inescapable: compensation.

Substantial disparities between what primary care physicians earn relative to specialists like orthopedists and cardiologists can weigh into medical students’ decisions about which field to choose. Plus, the system that Medicare and other health plans use to pay doctors generally places more value on doing procedures like replacing a knee or inserting a stent than on delivering the whole-person, long-term health care management that primary care physicians provide.

As a result of those pay disparities, and the punishing workload typically faced by primary care physicians, more new doctors are becoming specialists, often leaving patients with fewer choices for primary care.

“There is a public out there that is dissatisfied with the lack of access to a routine source of care,” said Christopher Koller, president of the Milbank Memorial Fund, a foundation that focuses on improving population health and health equity. “That’s not going to be addressed until we pay for it.”

Primary care is the foundation of our health care system, the only area in which providing more services – such as childhood vaccines and regular blood pressure screenings – is linked to better population health and more equitable outcomes, according to the National Academies of Sciences, Engineering, and Medicine, in a recently published report on how to rebuild primary care. Without it, the national academies wrote, “minor health problems can spiral into chronic disease,” with poor disease management, ED overuse, and unsustainable costs. Yet for decades, the United States has underinvested in primary care. It accounted for less than 5% of health care spending in 2020 – significantly less than the average spending by countries that are members of the Organization for Economic Cooperation and Development, according to the report.

A $26 billion piece of bipartisan legislation proposed last month by Sen. Bernie Sanders (I-Vt.), chair of the Senate Health, Education, Labor, and Pensions Committee, and Sen. Roger Marshall (R-Kan.) would bolster primary care by increasing training opportunities for doctors and nurses and expanding access to community health centers. Policy experts say the bill would provide important support, but it’s not enough. It doesn’t touch compensation.

“We need primary care to be paid differently and to be paid more, and that starts with Medicare,” Mr. Koller said.
 

How Medicare drives payment

Medicare, which covers 65 million people who are 65 and older or who have certain long-term disabilities, finances more than a fifth of all health care spending — giving it significant muscle in the health care market. Private health plans typically base their payment amounts on the Medicare system, so what Medicare pays is crucial.

Under the Medicare payment system, the amount the program pays for a medical service is determined by three geographically weighted components: a physician’s work, including time and intensity; the practice’s expense, such as overhead and equipment; and professional insurance. It tends to reward specialties that emphasize procedures, such as repairing a hernia or removing a tumor, more than primary care, where the focus is on talking with patients, answering questions, and educating them about managing their chronic conditions.

Medical students may not be familiar with the particulars of how the payment system works, but their clinical training exposes them to a punishing workload and burnout that is contributing to the shortage of primary care physicians, projected to reach up to 48,000 by 2034, according to estimates from the Association of American Medical Colleges.

The earnings differential between primary care and other specialists is also not lost on them. Average annual compensation for doctors who focus on primary care – family medicine, internists, and pediatricians – ranges from an average of about $250,000 to $275,000, according to Medscape’s annual physician compensation report. Many specialists make more than twice as much: Plastic surgeons top the compensation list at $619,000 annually, followed by orthopedists ($573,000) and cardiologists ($507,000).

“I think the major issues in terms of the primary care physician pipeline are the compensation and the work of primary care,” said Russ Phillips, MD, an internist and the director of the Harvard Medical School Center for Primary Care, Boston. “You have to really want to be a primary care physician when that student will make one-third of what students going into dermatology will make.”

According to statistics from the National Resident Matching Program, which tracks the number of residency slots available for graduating medical students and the number of slots filled, 89% of 5,088 family medicine residency slots were filled in 2023, compared with a 93% residency fill rate overall. Internists had a higher fill rate, 96%, but a significant proportion of internal medicine residents eventually practice in a specialty area rather than in primary care.

No one would claim that doctors are poorly paid, but with the average medical student graduating with just over $200,000 in medical school debt, making a good salary matters.
 

Not in it for the money

Still, it’s a misperception that student debt always drives the decision whether to go into primary care, said Len Marquez, senior director of government relations and legislative advocacy at the Association of American Medical Colleges.

For Anitza Quintero, 24, a second-year medical student at the Geisinger Commonwealth School of Medicine in rural Pennsylvania, primary care is a logical extension of her interest in helping children and immigrants. Ms. Quintero’s family came to the United States on a raft from Cuba before she was born. She plans to focus on internal medicine and pediatrics.

“I want to keep going to help my family and other families,” Ms. Quintero said. “There’s obviously something attractive about having a specialty and a high pay grade,” Still, she wants to work “where the whole body is involved,” she said, adding that long-term doctor-patient relationships are “also attractive.”

Ms. Quintero is part of the Abigail Geisinger Scholars Program, which aims to recruit primary care physicians and psychiatrists to the rural health system in part with a promise of medical school loan forgiveness. Health care shortages tend to be more acute in rural areas.

These students’ education costs are covered, and they receive a $2,000 monthly stipend. They can do their residency elsewhere, but upon completing it they return to Geisinger for a primary care job with the health care system. Every year of work there erases one year of the debt covered by their award. If they don’t take a job with the health care system, they must repay the amount they received.
 

Payment imbalances a source of tension

In recent years, the Centers for Medicare & Medicaid Services, which administers the Medicare program, has made changes to address some of the payment imbalances between primary care and specialist services. The agency has expanded the office visit services for which providers can bill to manage their patients, including adding nonprocedural billing codes for providing transitional care, chronic care management, and advance care planning.

In 2024’s final physician fee schedule, the agency plans to allow another new code to take effect, G2211. It would let physicians bill for complex patient evaluation and management services. Any physician could use the code, but it is expected that primary care physicians would use it more frequently than specialists. Congress has delayed implementation of the code since 2021.

The new code is a tiny piece of overall payment reform, “but it is critically important, and it is our top priority on the Hill right now,” said Shari Erickson, chief advocacy officer for the American College of Physicians.

It also triggered a tussle that highlights ongoing tension in Medicare physician payment rules.

The American College of Surgeons and 18 other specialty groups published a statement describing the new code as “unnecessary.” They oppose its implementation because it would primarily benefit primary care providers who, they say, already have the flexibility to bill more for more complex visits.

But the real issue is that, under federal law, changes to Medicare physician payments must preserve budget neutrality, a zero-sum arrangement in which payment increases for primary care providers mean payment decreases elsewhere.

“If they want to keep it, they need to pay for it,” said Christian Shalgian, director of the division of advocacy and health policy for the American College of Surgeons, noting that his organization will continue to oppose implementation otherwise.

Still, there’s general agreement that strengthening the primary care system through payment reform won’t be accomplished by tinkering with billing codes.

The current fee-for-service system doesn’t fully accommodate the time and effort primary care physicians put into “small-ticket” activities like emails and phone calls, reviews of lab results, and consultation reports. A better arrangement, they say, would be to pay primary care physicians a set monthly amount per patient to provide all their care, a system called capitation.

“We’re much better off paying on a per capita basis, get that monthly payment paid in advance plus some extra amount for other things,” said Paul Ginsburg, PhD, a senior fellow at the University of Southern California Schaeffer Center for Health Policy and Economics and former commissioner of the Medicare Payment Advisory Commission.

But if adding a single five-character code to Medicare’s payment rules has proved challenging, imagine the heavy lift involved in overhauling the program’s entire physician payment system. MedPAC and the national academies, both of which provide advice to Congress, have weighed in on the broad outlines of what such a transformation might look like. And there are targeted efforts in Congress: For instance, a bill that would add an annual inflation update to Medicare physician payments and a proposal to address budget neutrality. But it’s unclear whether lawmakers have strong interest in taking action.

“The fact that Medicare has been squeezing physician payment rates for 2 decades is making reforming their structure more difficult,” said Dr. Ginsburg. “The losers are more sensitive to reductions in the rates for the procedures they do.”

KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF—an independent source of health policy research, polling, and journalism. Learn more about KFF.

Money talks.

The United States faces a serious shortage of primary care physicians for many reasons, but one, in particular, is inescapable: compensation.

Substantial disparities between what primary care physicians earn relative to specialists like orthopedists and cardiologists can weigh into medical students’ decisions about which field to choose. Plus, the system that Medicare and other health plans use to pay doctors generally places more value on doing procedures like replacing a knee or inserting a stent than on delivering the whole-person, long-term health care management that primary care physicians provide.

As a result of those pay disparities, and the punishing workload typically faced by primary care physicians, more new doctors are becoming specialists, often leaving patients with fewer choices for primary care.

“There is a public out there that is dissatisfied with the lack of access to a routine source of care,” said Christopher Koller, president of the Milbank Memorial Fund, a foundation that focuses on improving population health and health equity. “That’s not going to be addressed until we pay for it.”

Primary care is the foundation of our health care system, the only area in which providing more services – such as childhood vaccines and regular blood pressure screenings – is linked to better population health and more equitable outcomes, according to the National Academies of Sciences, Engineering, and Medicine, in a recently published report on how to rebuild primary care. Without it, the national academies wrote, “minor health problems can spiral into chronic disease,” with poor disease management, ED overuse, and unsustainable costs. Yet for decades, the United States has underinvested in primary care. It accounted for less than 5% of health care spending in 2020 – significantly less than the average spending by countries that are members of the Organization for Economic Cooperation and Development, according to the report.

A $26 billion piece of bipartisan legislation proposed last month by Sen. Bernie Sanders (I-Vt.), chair of the Senate Health, Education, Labor, and Pensions Committee, and Sen. Roger Marshall (R-Kan.) would bolster primary care by increasing training opportunities for doctors and nurses and expanding access to community health centers. Policy experts say the bill would provide important support, but it’s not enough. It doesn’t touch compensation.

“We need primary care to be paid differently and to be paid more, and that starts with Medicare,” Mr. Koller said.
 

How Medicare drives payment

Medicare, which covers 65 million people who are 65 and older or who have certain long-term disabilities, finances more than a fifth of all health care spending — giving it significant muscle in the health care market. Private health plans typically base their payment amounts on the Medicare system, so what Medicare pays is crucial.

Under the Medicare payment system, the amount the program pays for a medical service is determined by three geographically weighted components: a physician’s work, including time and intensity; the practice’s expense, such as overhead and equipment; and professional insurance. It tends to reward specialties that emphasize procedures, such as repairing a hernia or removing a tumor, more than primary care, where the focus is on talking with patients, answering questions, and educating them about managing their chronic conditions.

Medical students may not be familiar with the particulars of how the payment system works, but their clinical training exposes them to a punishing workload and burnout that is contributing to the shortage of primary care physicians, projected to reach up to 48,000 by 2034, according to estimates from the Association of American Medical Colleges.

The earnings differential between primary care and other specialists is also not lost on them. Average annual compensation for doctors who focus on primary care – family medicine, internists, and pediatricians – ranges from an average of about $250,000 to $275,000, according to Medscape’s annual physician compensation report. Many specialists make more than twice as much: Plastic surgeons top the compensation list at $619,000 annually, followed by orthopedists ($573,000) and cardiologists ($507,000).

“I think the major issues in terms of the primary care physician pipeline are the compensation and the work of primary care,” said Russ Phillips, MD, an internist and the director of the Harvard Medical School Center for Primary Care, Boston. “You have to really want to be a primary care physician when that student will make one-third of what students going into dermatology will make.”

According to statistics from the National Resident Matching Program, which tracks the number of residency slots available for graduating medical students and the number of slots filled, 89% of 5,088 family medicine residency slots were filled in 2023, compared with a 93% residency fill rate overall. Internists had a higher fill rate, 96%, but a significant proportion of internal medicine residents eventually practice in a specialty area rather than in primary care.

No one would claim that doctors are poorly paid, but with the average medical student graduating with just over $200,000 in medical school debt, making a good salary matters.
 

Not in it for the money

Still, it’s a misperception that student debt always drives the decision whether to go into primary care, said Len Marquez, senior director of government relations and legislative advocacy at the Association of American Medical Colleges.

For Anitza Quintero, 24, a second-year medical student at the Geisinger Commonwealth School of Medicine in rural Pennsylvania, primary care is a logical extension of her interest in helping children and immigrants. Ms. Quintero’s family came to the United States on a raft from Cuba before she was born. She plans to focus on internal medicine and pediatrics.

“I want to keep going to help my family and other families,” Ms. Quintero said. “There’s obviously something attractive about having a specialty and a high pay grade,” Still, she wants to work “where the whole body is involved,” she said, adding that long-term doctor-patient relationships are “also attractive.”

Ms. Quintero is part of the Abigail Geisinger Scholars Program, which aims to recruit primary care physicians and psychiatrists to the rural health system in part with a promise of medical school loan forgiveness. Health care shortages tend to be more acute in rural areas.

These students’ education costs are covered, and they receive a $2,000 monthly stipend. They can do their residency elsewhere, but upon completing it they return to Geisinger for a primary care job with the health care system. Every year of work there erases one year of the debt covered by their award. If they don’t take a job with the health care system, they must repay the amount they received.
 

Payment imbalances a source of tension

In recent years, the Centers for Medicare & Medicaid Services, which administers the Medicare program, has made changes to address some of the payment imbalances between primary care and specialist services. The agency has expanded the office visit services for which providers can bill to manage their patients, including adding nonprocedural billing codes for providing transitional care, chronic care management, and advance care planning.

In 2024’s final physician fee schedule, the agency plans to allow another new code to take effect, G2211. It would let physicians bill for complex patient evaluation and management services. Any physician could use the code, but it is expected that primary care physicians would use it more frequently than specialists. Congress has delayed implementation of the code since 2021.

The new code is a tiny piece of overall payment reform, “but it is critically important, and it is our top priority on the Hill right now,” said Shari Erickson, chief advocacy officer for the American College of Physicians.

It also triggered a tussle that highlights ongoing tension in Medicare physician payment rules.

The American College of Surgeons and 18 other specialty groups published a statement describing the new code as “unnecessary.” They oppose its implementation because it would primarily benefit primary care providers who, they say, already have the flexibility to bill more for more complex visits.

But the real issue is that, under federal law, changes to Medicare physician payments must preserve budget neutrality, a zero-sum arrangement in which payment increases for primary care providers mean payment decreases elsewhere.

“If they want to keep it, they need to pay for it,” said Christian Shalgian, director of the division of advocacy and health policy for the American College of Surgeons, noting that his organization will continue to oppose implementation otherwise.

Still, there’s general agreement that strengthening the primary care system through payment reform won’t be accomplished by tinkering with billing codes.

The current fee-for-service system doesn’t fully accommodate the time and effort primary care physicians put into “small-ticket” activities like emails and phone calls, reviews of lab results, and consultation reports. A better arrangement, they say, would be to pay primary care physicians a set monthly amount per patient to provide all their care, a system called capitation.

“We’re much better off paying on a per capita basis, get that monthly payment paid in advance plus some extra amount for other things,” said Paul Ginsburg, PhD, a senior fellow at the University of Southern California Schaeffer Center for Health Policy and Economics and former commissioner of the Medicare Payment Advisory Commission.

But if adding a single five-character code to Medicare’s payment rules has proved challenging, imagine the heavy lift involved in overhauling the program’s entire physician payment system. MedPAC and the national academies, both of which provide advice to Congress, have weighed in on the broad outlines of what such a transformation might look like. And there are targeted efforts in Congress: For instance, a bill that would add an annual inflation update to Medicare physician payments and a proposal to address budget neutrality. But it’s unclear whether lawmakers have strong interest in taking action.

“The fact that Medicare has been squeezing physician payment rates for 2 decades is making reforming their structure more difficult,” said Dr. Ginsburg. “The losers are more sensitive to reductions in the rates for the procedures they do.”

KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF—an independent source of health policy research, polling, and journalism. Learn more about KFF.

A 40-year-old women is evaluated for liver abnormalities. She had elevated transaminases and alkaline phosphatase. A liver ultrasound showed multiple lesions. She underwent liver biopsy, which showed granulomas. What test results, if abnormal, would be most suggestive of sarcoidosis?

A. Erythrocyte sedimentation rate

B. C-reactive protein

C. Lymphocyte count

D. Antinuclear antibodies

The correct answer here is lymphocyte count. Sarcoidosis is in just about every differential diagnosis, as it can involve every organ system. I will share with you a few pearls I have learned over 30 years of taking care of patients with sarcoidosis. Lymphocyte counts drop with active sarcoidosis. Sarcoidosis should always be part of the differential when you see lymphopenia. El Jammal et al. studied 90 patients referred for possible granulomatous hepatitis.¹ Seventy-three patients had a final diagnosis of granulomatous hepatitis, and 38 of those patients had sarcoidosis. Lymphopenia had a high specificity (85.7%) for the diagnosis of sarcoidosis, with a specificity of 100% in the patients under 50 years old.

Morell and colleagues looked at whether low lymphocyte counts and low lymphocyte percentage were markers of active sarcoidosis.² Forty patients with biopsy-proven sarcoidosis were prospectively evaluated every 6 months. A low lymphocyte count and a low lymphocyte percentage (< 20%) were detected more frequently in patients with active sarcoidosis than in the patients with asymptomatic sarcoidosis (P < .02 and P < .0001).

Jones et al. looked at lymphopenia as a marker of sarcoidosis in patients presenting with uveitis.³ The study was a retrospective case-control study (112 patients with sarcoidosis-associated uveitis and 398 controls with other forms of uveitis). The mean lymphocyte count for patients with sarcoidosis was 1.43 vs. 2.04 for other causes of uveitis (P ≤ .0001).

Patients with sarcoidosis are at risk of hypercalciuria, hypercalcemia, and kidney stones. These are common in patients with sarcoidosis, with up to 50% of such patients having hypercalciuria. This is because in sarcoidosis patients 25(OH) vitamin D is converted in granulomas by activated macrophages to 1,25(OH)₂ vitamin D, which is the active form of vitamin D.

Several studies have looked at the diagnostic utility of 1,25(OH)₂ vitamin D levels in patients with suspected sarcoidosis. Rohmer and colleagues looked at whether 1,25(OH)₂ vitamin D levels could help with the diagnosis of sarcoidosis as the cause of uveitis.⁴ They found that the level of 25(OH) vitamin D in sarcoidosis patients with uveitis was lower than in patients with uveitis without sarcoidosis, 34 vs. 43 nmol/mL (P < .02), whereas the 1,25(OH)₂ vitamin D level was higher in patients with sarcoidosis than in those with uveitis without sarcoidosis, 132 vs. 108 pmol/L (P = .02). They looked at the 1,25(OH)₂D/25(OH)D ratio; a ratio > 3.5 was strongly associated with an abnormal chest CT-scan (OR = 5.7, P = .003) and granulomas on bronchial biopsy (OR = 14.7, P = .007).

Kavathia et al. looked at whether elevated 1,25(OH)₂ vitamin D levels predicted chronicity of sarcoidosis.⁵ A total of 59 sarcoidosis patients were recruited for the study. Higher serum 1,25(OH)₂ vitamin D levels were associated with patients requiring repeated systemic immunosuppressive therapy or > 1 year of therapy. Increasing quartiles of serum 1,25(OH)₂ vitamin D level were associated with increased odds of patients having chronic sarcoidosis (OR = 1.82; 95% CI, 1.11-2.99, P = .019).

Because of the higher activated vitamin D levels in sarcoidosis patients, they are at risk for problems with vitamin D supplementation. I have seen two patients develop large numbers of kidney stones after receiving high-dose vitamin D. Sodhi and Aldrich reported on a cohort of 196 sarcoidosis patients who had received vitamin D and compared them with 196 control patients with sarcoidosis who were not receiving vitamin D.⁶ Hypercalcemia was more frequent in the group that received vitamin D (42.3%) than in the group that did not (18.3%, P < .0001). In this study, only a minority (23%) of patients receiving vitamin D had their 1,25(OH)₂ vitamin D level checked.


Pearl: Lymphocyte count and 1,25(OH)₂ vitamin D levels can be helpful tests in assessing sarcoidosis activity. Patients with sarcoidosis who receive vitamin D should have their 1.25(OH)₂ vitamin D levels monitored.

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at [email protected].

References

1. El Jammal et al. Sarcoidosis Vasc Diffuse Lung Dis. 2023 Sep 13;40(3):e2023031.

2. Morell F et al. Chest. 2002 Apr;121(4):1239-44.

3. Jones NP et al. Br J Ophthalmol. 2016 Oct;100(10):1393-6.

4. Rohmer J et al. Ocul Immunol Inflamm. 2020 Apr 2;28(3):341-7.

5. Kavathia D et al. Respir Med. 2010 Apr;104(4):564–70.

6. Sodhi A and Aldrich T. Am J Med Sci. 2016 Sep;352(3):252-7.

A 40-year-old women is evaluated for liver abnormalities. She had elevated transaminases and alkaline phosphatase. A liver ultrasound showed multiple lesions. She underwent liver biopsy, which showed granulomas. What test results, if abnormal, would be most suggestive of sarcoidosis?

A. Erythrocyte sedimentation rate

B. C-reactive protein

C. Lymphocyte count

D. Antinuclear antibodies

The correct answer here is lymphocyte count. Sarcoidosis is in just about every differential diagnosis, as it can involve every organ system. I will share with you a few pearls I have learned over 30 years of taking care of patients with sarcoidosis. Lymphocyte counts drop with active sarcoidosis. Sarcoidosis should always be part of the differential when you see lymphopenia. El Jammal et al. studied 90 patients referred for possible granulomatous hepatitis.¹ Seventy-three patients had a final diagnosis of granulomatous hepatitis, and 38 of those patients had sarcoidosis. Lymphopenia had a high specificity (85.7%) for the diagnosis of sarcoidosis, with a specificity of 100% in the patients under 50 years old.

Morell and colleagues looked at whether low lymphocyte counts and low lymphocyte percentage were markers of active sarcoidosis.² Forty patients with biopsy-proven sarcoidosis were prospectively evaluated every 6 months. A low lymphocyte count and a low lymphocyte percentage (< 20%) were detected more frequently in patients with active sarcoidosis than in the patients with asymptomatic sarcoidosis (P < .02 and P < .0001).

Jones et al. looked at lymphopenia as a marker of sarcoidosis in patients presenting with uveitis.³ The study was a retrospective case-control study (112 patients with sarcoidosis-associated uveitis and 398 controls with other forms of uveitis). The mean lymphocyte count for patients with sarcoidosis was 1.43 vs. 2.04 for other causes of uveitis (P ≤ .0001).

Patients with sarcoidosis are at risk of hypercalciuria, hypercalcemia, and kidney stones. These are common in patients with sarcoidosis, with up to 50% of such patients having hypercalciuria. This is because in sarcoidosis patients 25(OH) vitamin D is converted in granulomas by activated macrophages to 1,25(OH)₂ vitamin D, which is the active form of vitamin D.

Several studies have looked at the diagnostic utility of 1,25(OH)₂ vitamin D levels in patients with suspected sarcoidosis. Rohmer and colleagues looked at whether 1,25(OH)₂ vitamin D levels could help with the diagnosis of sarcoidosis as the cause of uveitis.⁴ They found that the level of 25(OH) vitamin D in sarcoidosis patients with uveitis was lower than in patients with uveitis without sarcoidosis, 34 vs. 43 nmol/mL (P < .02), whereas the 1,25(OH)₂ vitamin D level was higher in patients with sarcoidosis than in those with uveitis without sarcoidosis, 132 vs. 108 pmol/L (P = .02). They looked at the 1,25(OH)₂D/25(OH)D ratio; a ratio > 3.5 was strongly associated with an abnormal chest CT-scan (OR = 5.7, P = .003) and granulomas on bronchial biopsy (OR = 14.7, P = .007).

Kavathia et al. looked at whether elevated 1,25(OH)₂ vitamin D levels predicted chronicity of sarcoidosis.⁵ A total of 59 sarcoidosis patients were recruited for the study. Higher serum 1,25(OH)₂ vitamin D levels were associated with patients requiring repeated systemic immunosuppressive therapy or > 1 year of therapy. Increasing quartiles of serum 1,25(OH)₂ vitamin D level were associated with increased odds of patients having chronic sarcoidosis (OR = 1.82; 95% CI, 1.11-2.99, P = .019).

Because of the higher activated vitamin D levels in sarcoidosis patients, they are at risk for problems with vitamin D supplementation. I have seen two patients develop large numbers of kidney stones after receiving high-dose vitamin D. Sodhi and Aldrich reported on a cohort of 196 sarcoidosis patients who had received vitamin D and compared them with 196 control patients with sarcoidosis who were not receiving vitamin D.⁶ Hypercalcemia was more frequent in the group that received vitamin D (42.3%) than in the group that did not (18.3%, P < .0001). In this study, only a minority (23%) of patients receiving vitamin D had their 1,25(OH)₂ vitamin D level checked.


Pearl: Lymphocyte count and 1,25(OH)₂ vitamin D levels can be helpful tests in assessing sarcoidosis activity. Patients with sarcoidosis who receive vitamin D should have their 1.25(OH)₂ vitamin D levels monitored.

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at [email protected].

References

1. El Jammal et al. Sarcoidosis Vasc Diffuse Lung Dis. 2023 Sep 13;40(3):e2023031.

2. Morell F et al. Chest. 2002 Apr;121(4):1239-44.

3. Jones NP et al. Br J Ophthalmol. 2016 Oct;100(10):1393-6.

4. Rohmer J et al. Ocul Immunol Inflamm. 2020 Apr 2;28(3):341-7.

5. Kavathia D et al. Respir Med. 2010 Apr;104(4):564–70.

6. Sodhi A and Aldrich T. Am J Med Sci. 2016 Sep;352(3):252-7.

A 40-year-old women is evaluated for liver abnormalities. She had elevated transaminases and alkaline phosphatase. A liver ultrasound showed multiple lesions. She underwent liver biopsy, which showed granulomas. What test results, if abnormal, would be most suggestive of sarcoidosis?

A. Erythrocyte sedimentation rate

B. C-reactive protein

C. Lymphocyte count

D. Antinuclear antibodies

The correct answer here is lymphocyte count. Sarcoidosis is in just about every differential diagnosis, as it can involve every organ system. I will share with you a few pearls I have learned over 30 years of taking care of patients with sarcoidosis. Lymphocyte counts drop with active sarcoidosis. Sarcoidosis should always be part of the differential when you see lymphopenia. El Jammal et al. studied 90 patients referred for possible granulomatous hepatitis.¹ Seventy-three patients had a final diagnosis of granulomatous hepatitis, and 38 of those patients had sarcoidosis. Lymphopenia had a high specificity (85.7%) for the diagnosis of sarcoidosis, with a specificity of 100% in the patients under 50 years old.

Morell and colleagues looked at whether low lymphocyte counts and low lymphocyte percentage were markers of active sarcoidosis.² Forty patients with biopsy-proven sarcoidosis were prospectively evaluated every 6 months. A low lymphocyte count and a low lymphocyte percentage (< 20%) were detected more frequently in patients with active sarcoidosis than in the patients with asymptomatic sarcoidosis (P < .02 and P < .0001).

Jones et al. looked at lymphopenia as a marker of sarcoidosis in patients presenting with uveitis.³ The study was a retrospective case-control study (112 patients with sarcoidosis-associated uveitis and 398 controls with other forms of uveitis). The mean lymphocyte count for patients with sarcoidosis was 1.43 vs. 2.04 for other causes of uveitis (P ≤ .0001).

Patients with sarcoidosis are at risk of hypercalciuria, hypercalcemia, and kidney stones. These are common in patients with sarcoidosis, with up to 50% of such patients having hypercalciuria. This is because in sarcoidosis patients 25(OH) vitamin D is converted in granulomas by activated macrophages to 1,25(OH)₂ vitamin D, which is the active form of vitamin D.

Several studies have looked at the diagnostic utility of 1,25(OH)₂ vitamin D levels in patients with suspected sarcoidosis. Rohmer and colleagues looked at whether 1,25(OH)₂ vitamin D levels could help with the diagnosis of sarcoidosis as the cause of uveitis.⁴ They found that the level of 25(OH) vitamin D in sarcoidosis patients with uveitis was lower than in patients with uveitis without sarcoidosis, 34 vs. 43 nmol/mL (P < .02), whereas the 1,25(OH)₂ vitamin D level was higher in patients with sarcoidosis than in those with uveitis without sarcoidosis, 132 vs. 108 pmol/L (P = .02). They looked at the 1,25(OH)₂D/25(OH)D ratio; a ratio > 3.5 was strongly associated with an abnormal chest CT-scan (OR = 5.7, P = .003) and granulomas on bronchial biopsy (OR = 14.7, P = .007).

Kavathia et al. looked at whether elevated 1,25(OH)₂ vitamin D levels predicted chronicity of sarcoidosis.⁵ A total of 59 sarcoidosis patients were recruited for the study. Higher serum 1,25(OH)₂ vitamin D levels were associated with patients requiring repeated systemic immunosuppressive therapy or > 1 year of therapy. Increasing quartiles of serum 1,25(OH)₂ vitamin D level were associated with increased odds of patients having chronic sarcoidosis (OR = 1.82; 95% CI, 1.11-2.99, P = .019).

Because of the higher activated vitamin D levels in sarcoidosis patients, they are at risk for problems with vitamin D supplementation. I have seen two patients develop large numbers of kidney stones after receiving high-dose vitamin D. Sodhi and Aldrich reported on a cohort of 196 sarcoidosis patients who had received vitamin D and compared them with 196 control patients with sarcoidosis who were not receiving vitamin D.⁶ Hypercalcemia was more frequent in the group that received vitamin D (42.3%) than in the group that did not (18.3%, P < .0001). In this study, only a minority (23%) of patients receiving vitamin D had their 1,25(OH)₂ vitamin D level checked.


Pearl: Lymphocyte count and 1,25(OH)₂ vitamin D levels can be helpful tests in assessing sarcoidosis activity. Patients with sarcoidosis who receive vitamin D should have their 1.25(OH)₂ vitamin D levels monitored.

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at [email protected].

References

1. El Jammal et al. Sarcoidosis Vasc Diffuse Lung Dis. 2023 Sep 13;40(3):e2023031.

2. Morell F et al. Chest. 2002 Apr;121(4):1239-44.

3. Jones NP et al. Br J Ophthalmol. 2016 Oct;100(10):1393-6.

4. Rohmer J et al. Ocul Immunol Inflamm. 2020 Apr 2;28(3):341-7.

5. Kavathia D et al. Respir Med. 2010 Apr;104(4):564–70.

6. Sodhi A and Aldrich T. Am J Med Sci. 2016 Sep;352(3):252-7.

Women with bipolar disorder were three times more likely than were healthy controls to experience polycystic ovarian syndrome, based on data from nearly 250 individuals.

Previous studies suggest that the prevalence of polycystic ovarian syndrome (PCOS) is higher in bipolar disorder (BD) patients compared with individuals not diagnosed with BD, wrote Jieyu Liu, PhD, of the Second Xiangya Hospital of Central South University, Hunan, China, and colleagues.

However, studies have been limited to drug-treated BD patients, and data on the effects of BD on the development of PCOS are limited, they said. Data from previous studies also indicate that serum testosterone levels, serum androstenedione levels, and polycystic ovarian morphology (PCOM) are increased in BD patients compared with women without BD.

In a study published in the Journal of Affective Disorders, the researchers recruited 72 BD patients on long-term medication, 72 drug-naive patients, and 98 healthy controls between March 2022 and November 2022.

PCOM was assessed using ≥ 8 MHz transvaginal transducers to determine the number of follicles and ovarian volume. PCOS was then defined using the Rotterdam criteria, in which patients met two of three qualifications: oligoovulation or anovulation; hyperandrogenemia; or PCOM (excluding other endocrine diseases).

In a multivariate analysis, drug-naive women with BD had significantly higher rates of PCOS compared with healthy controls (odds ratio 3.02). The drug-naive BD patients also had a greater prevalence of oligoamenorrhea compared with healthy controls (36.36% vs. 12.12%) and higher levels of anti-mullerian hormone, luteinizing hormone, and follicle stimulating hormone compared to the controls.

A further regression analysis showed that those on long-term valproate treatment had the highest risk (OR 3.89) and the prevalence of PCOS was significantly higher among patients treated with valproate compared with drug-naive patients (53.3% vs. 30.6%). Younger age and the presence of insulin resistance also were associated with increased risk of PCOS (OR 0.37 and OR 1.73, respectively).

“Unexpectedly, no significant differences in serum androgen levels, including TT, FAI, androstenedione, and [dehydroepiandrosterone sulfate] levels, were observed between drug-naive BD patients and the HCs,” the researchers wrote in their discussion. This difference may stem from multiple causes including demographic variables, inclusion of PCOM as a diagnostic criterion, and the impact of genetic and environmental factors, they said.

The findings were limited by several factors including the small study population, which prevented conclusions of causality and comparison of the effects of different mood stabilizers on PCOS, the researchers noted. Other limitations included the relatively homogeneous population from a single region in China, and the inability to account for the effects of diet and lifestyle.

More research is needed to explore the impact of mediations, but the results suggest that BD patients are susceptible to PCOS; therefore, they should evaluate their reproductive health before starting any medication, and review reproductive health regularly, the researchers concluded.

The study was supported by the National Natural Science Foundation of China. The researchers had no financial conflicts to disclose.

Women with bipolar disorder were three times more likely than were healthy controls to experience polycystic ovarian syndrome, based on data from nearly 250 individuals.

Previous studies suggest that the prevalence of polycystic ovarian syndrome (PCOS) is higher in bipolar disorder (BD) patients compared with individuals not diagnosed with BD, wrote Jieyu Liu, PhD, of the Second Xiangya Hospital of Central South University, Hunan, China, and colleagues.

However, studies have been limited to drug-treated BD patients, and data on the effects of BD on the development of PCOS are limited, they said. Data from previous studies also indicate that serum testosterone levels, serum androstenedione levels, and polycystic ovarian morphology (PCOM) are increased in BD patients compared with women without BD.

In a study published in the Journal of Affective Disorders, the researchers recruited 72 BD patients on long-term medication, 72 drug-naive patients, and 98 healthy controls between March 2022 and November 2022.

PCOM was assessed using ≥ 8 MHz transvaginal transducers to determine the number of follicles and ovarian volume. PCOS was then defined using the Rotterdam criteria, in which patients met two of three qualifications: oligoovulation or anovulation; hyperandrogenemia; or PCOM (excluding other endocrine diseases).

In a multivariate analysis, drug-naive women with BD had significantly higher rates of PCOS compared with healthy controls (odds ratio 3.02). The drug-naive BD patients also had a greater prevalence of oligoamenorrhea compared with healthy controls (36.36% vs. 12.12%) and higher levels of anti-mullerian hormone, luteinizing hormone, and follicle stimulating hormone compared to the controls.

A further regression analysis showed that those on long-term valproate treatment had the highest risk (OR 3.89) and the prevalence of PCOS was significantly higher among patients treated with valproate compared with drug-naive patients (53.3% vs. 30.6%). Younger age and the presence of insulin resistance also were associated with increased risk of PCOS (OR 0.37 and OR 1.73, respectively).

“Unexpectedly, no significant differences in serum androgen levels, including TT, FAI, androstenedione, and [dehydroepiandrosterone sulfate] levels, were observed between drug-naive BD patients and the HCs,” the researchers wrote in their discussion. This difference may stem from multiple causes including demographic variables, inclusion of PCOM as a diagnostic criterion, and the impact of genetic and environmental factors, they said.

The findings were limited by several factors including the small study population, which prevented conclusions of causality and comparison of the effects of different mood stabilizers on PCOS, the researchers noted. Other limitations included the relatively homogeneous population from a single region in China, and the inability to account for the effects of diet and lifestyle.

More research is needed to explore the impact of mediations, but the results suggest that BD patients are susceptible to PCOS; therefore, they should evaluate their reproductive health before starting any medication, and review reproductive health regularly, the researchers concluded.

The study was supported by the National Natural Science Foundation of China. The researchers had no financial conflicts to disclose.

Women with bipolar disorder were three times more likely than were healthy controls to experience polycystic ovarian syndrome, based on data from nearly 250 individuals.

Previous studies suggest that the prevalence of polycystic ovarian syndrome (PCOS) is higher in bipolar disorder (BD) patients compared with individuals not diagnosed with BD, wrote Jieyu Liu, PhD, of the Second Xiangya Hospital of Central South University, Hunan, China, and colleagues.

However, studies have been limited to drug-treated BD patients, and data on the effects of BD on the development of PCOS are limited, they said. Data from previous studies also indicate that serum testosterone levels, serum androstenedione levels, and polycystic ovarian morphology (PCOM) are increased in BD patients compared with women without BD.

In a study published in the Journal of Affective Disorders, the researchers recruited 72 BD patients on long-term medication, 72 drug-naive patients, and 98 healthy controls between March 2022 and November 2022.

PCOM was assessed using ≥ 8 MHz transvaginal transducers to determine the number of follicles and ovarian volume. PCOS was then defined using the Rotterdam criteria, in which patients met two of three qualifications: oligoovulation or anovulation; hyperandrogenemia; or PCOM (excluding other endocrine diseases).

In a multivariate analysis, drug-naive women with BD had significantly higher rates of PCOS compared with healthy controls (odds ratio 3.02). The drug-naive BD patients also had a greater prevalence of oligoamenorrhea compared with healthy controls (36.36% vs. 12.12%) and higher levels of anti-mullerian hormone, luteinizing hormone, and follicle stimulating hormone compared to the controls.

A further regression analysis showed that those on long-term valproate treatment had the highest risk (OR 3.89) and the prevalence of PCOS was significantly higher among patients treated with valproate compared with drug-naive patients (53.3% vs. 30.6%). Younger age and the presence of insulin resistance also were associated with increased risk of PCOS (OR 0.37 and OR 1.73, respectively).

“Unexpectedly, no significant differences in serum androgen levels, including TT, FAI, androstenedione, and [dehydroepiandrosterone sulfate] levels, were observed between drug-naive BD patients and the HCs,” the researchers wrote in their discussion. This difference may stem from multiple causes including demographic variables, inclusion of PCOM as a diagnostic criterion, and the impact of genetic and environmental factors, they said.

The findings were limited by several factors including the small study population, which prevented conclusions of causality and comparison of the effects of different mood stabilizers on PCOS, the researchers noted. Other limitations included the relatively homogeneous population from a single region in China, and the inability to account for the effects of diet and lifestyle.

More research is needed to explore the impact of mediations, but the results suggest that BD patients are susceptible to PCOS; therefore, they should evaluate their reproductive health before starting any medication, and review reproductive health regularly, the researchers concluded.

The study was supported by the National Natural Science Foundation of China. The researchers had no financial conflicts to disclose.

SAN DIEGO – Monthly use of intravenously administered secukinumab (Cosentyx) proved its efficacy over placebo in treating psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA) in two industry-sponsored, randomized, double-blinded, phase 3 trials of the drug’s second and newly approved route of administration.

The studies of the human monoclonal antibody secukinumab, an interleukin-17 inhibitor, were presented at the annual meeting of the American College of Rheumatology. A subcutaneously injectable formulation of the drug is available, and the Food and Drug Administration approved the IV form for the conditions in October, although at a recommended lower monthly dose than the new trials examined.

In the PsA trial, 191 patients took IV secukinumab, and 190 took placebo. For the primary endpoint, the percentages who reached at least a 50% improvement in American College of Rheumatology response criteria (ACR 50) at 16 weeks were 31.4% and 6.3%, respectively (P < .0001).

In the axSpA trial, 264 patients took IV secukinumab, and 262 took placebo. The primary endpoint, at least a 40% improvement in Assessment of the Spondyloarthritis International Society response criteria (ASAS 40), was met at 16 weeks by 40.9% and 22.9%, respectively (P < .0001).

“Both studies appear to present clear efficacy of IV route administration of secukinumab with no clear increase in safety signals,” consultant rheumatologist Nicola Goodson, MBChB, PhD, of Aintree University Hospital in Liverpool, England, said in an interview.

“Offering IV administration as an option to patients is helpful,” added Dr. Goodson, who was not involved with the study but is familiar with its findings.

As Dr. Goodson explained, secukinumab “was the first IL [interleukin]-17 inhibitor used to treat spondyloarthropathies, and we have been using subcutaneous secukinumab to treat psoriasis, psoriatic arthritis, and axial spondyloarthritis/ankylosing spondylitis since 2016 in the U.K. Our experience with this medication has been good with similar efficacy to anti-TNF [tumor necrosis factor] therapy in axial spondyloarthritis. The medication is generally well-tolerated, and the subcutaneous pen injection device is easy for patients to use.”

However, IV treatment may speed up onset of action, she said, and it may be useful in situations when compliance is a challenge.
 

PsA trial details

In the PsA trial, known as INVIGORATE-2, researchers recruited patients who met the CASPAR criteria for active PsA with symptoms for ≥ 6 months, and had ≥ 3 tender joints out of 78 joints and ≥ 3 swollen joints out of 76.

Participants with a mean age of 48, including 55% females, were randomized 1:1 to receive placebo or secukinumab (6 mg/kg at baseline followed by 3 mg/kg every 4 weeks). Those in the placebo group were switched to the same monthly doses of secukinumab at 16 weeks.

“Patients who switched from the placebo had a similar increase of efficacy as the original treated group,” rheumatologist Alan J. Kivitz, MD, of the Altoona Center for Clinical Research, in Duncansville, Penn., said in his presentation at the meeting. Specifically, at 52 weeks, the groups had similar ACR 50 response rates: 58% with secukinumab and 64% with placebo-to-secukinumab.

The fact that patients in the original placebo group who received 3 mg IV doses without 6-mg loading doses achieved ACR response rates similar to those who took secukinumab during the whole trial “could suggest that the IV loading dose may not be required. This would need to be explored in a randomized head-to-head study, but it’s an interesting observation that may reduce costs and exposure to higher doses of medication at the start of treatment,” Dr. Goodson said.

Among the patients who received secukinumab at any point in the study, 63% had a treatment-emergent adverse event, including 5.9% with serious events. One death was reported in the placebo group before week 16. No other deaths were reported.
 

AxSpA trial details

In the axSpA trial, called INVIGORATE-1, researchers recruited people aged ≥18 years with a diagnosis of active radiographic axSpA according to modified New York criteria or nonradiographic axSpA according to ASAS criteria, and all had inflammatory back pain for ≥6 months with an onset before age 45. They were randomized at a 1:1 ratio to receive IV secukinumab (6 mg/kg loading dose, followed by 3 mg/kg every 4 weeks) or placebo for 16 weeks. At that point, the placebo group switched to the same monthly doses of IV secukinumab.

Participants had a mean age of about 39, and about one-third were female.

Following the statistical superiority in ASAS 40 response rates seen with IV secukinumab at week 16, patients who from there switched from placebo to IV secukinumab achieved comparable ASAS 40 response rates to those of patients originally randomized to secukinumab by week 24, reaching 66.8% for those on secukinumab the whole time and 74.9% for those who switched.

Secondary outcome measures were similar in both groups at week 52.

Among all patients who took secukinumab – the percentage with any adverse event was 63.2%, and 6% had a nonfatal adverse event deemed serious. There was one death during secukinumab treatment not suspected to be related to treatment.

In a presentation about the axSpA study findings, Atul Deodhar, MD, of Oregon Health & Science University, noted that “having an IV biologic available in the U.S. has some advantages. There are certain insurance providers such as Medicare where it is more economical for the patient to have an IV drug available.”

Dr. Deodhar also noted that in October the FDA approved a recommended lower dose for the IV treatment than in the study: 1.75 mg/kg instead of 3 mg/kg following the loading dose. That’s because the 3 mg/kg dose caused blood levels to be higher than those in the subcutaneous form, he said.

The FDA made the same dose recommendation for PsA.
 

Study limitations

Dr. Goodson, the U.K. consultant rheumatologist, noted a limitation of the trials: “It would have been interesting to compare IV to subcutaneous route secukinumab.” Still, the findings suggest that “the safety and efficacy of IV administration appears comparable,” she said.

“IV administration will have associated costs of attending hospital or infusion clinics,” she added, “and the cost of additional staff and administration need to be considered.”

Novartis, the maker of secukinumab, funded both studies. The PsA study authors report multiple relationships with industry, and some, such as Dr. Kivitz, have connections to Novartis. The axSpA study authors also report multiple relationships with industry, and some, such as Dr. Deodhar, have connections to Novartis. Some authors of both studies are Novartis employees. Dr. Goodson disclosed financial relationships with UCB and AbbVie.

SAN DIEGO – Monthly use of intravenously administered secukinumab (Cosentyx) proved its efficacy over placebo in treating psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA) in two industry-sponsored, randomized, double-blinded, phase 3 trials of the drug’s second and newly approved route of administration.

The studies of the human monoclonal antibody secukinumab, an interleukin-17 inhibitor, were presented at the annual meeting of the American College of Rheumatology. A subcutaneously injectable formulation of the drug is available, and the Food and Drug Administration approved the IV form for the conditions in October, although at a recommended lower monthly dose than the new trials examined.

In the PsA trial, 191 patients took IV secukinumab, and 190 took placebo. For the primary endpoint, the percentages who reached at least a 50% improvement in American College of Rheumatology response criteria (ACR 50) at 16 weeks were 31.4% and 6.3%, respectively (P < .0001).

In the axSpA trial, 264 patients took IV secukinumab, and 262 took placebo. The primary endpoint, at least a 40% improvement in Assessment of the Spondyloarthritis International Society response criteria (ASAS 40), was met at 16 weeks by 40.9% and 22.9%, respectively (P < .0001).

“Both studies appear to present clear efficacy of IV route administration of secukinumab with no clear increase in safety signals,” consultant rheumatologist Nicola Goodson, MBChB, PhD, of Aintree University Hospital in Liverpool, England, said in an interview.

“Offering IV administration as an option to patients is helpful,” added Dr. Goodson, who was not involved with the study but is familiar with its findings.

As Dr. Goodson explained, secukinumab “was the first IL [interleukin]-17 inhibitor used to treat spondyloarthropathies, and we have been using subcutaneous secukinumab to treat psoriasis, psoriatic arthritis, and axial spondyloarthritis/ankylosing spondylitis since 2016 in the U.K. Our experience with this medication has been good with similar efficacy to anti-TNF [tumor necrosis factor] therapy in axial spondyloarthritis. The medication is generally well-tolerated, and the subcutaneous pen injection device is easy for patients to use.”

However, IV treatment may speed up onset of action, she said, and it may be useful in situations when compliance is a challenge.
 

PsA trial details

In the PsA trial, known as INVIGORATE-2, researchers recruited patients who met the CASPAR criteria for active PsA with symptoms for ≥ 6 months, and had ≥ 3 tender joints out of 78 joints and ≥ 3 swollen joints out of 76.

Participants with a mean age of 48, including 55% females, were randomized 1:1 to receive placebo or secukinumab (6 mg/kg at baseline followed by 3 mg/kg every 4 weeks). Those in the placebo group were switched to the same monthly doses of secukinumab at 16 weeks.

“Patients who switched from the placebo had a similar increase of efficacy as the original treated group,” rheumatologist Alan J. Kivitz, MD, of the Altoona Center for Clinical Research, in Duncansville, Penn., said in his presentation at the meeting. Specifically, at 52 weeks, the groups had similar ACR 50 response rates: 58% with secukinumab and 64% with placebo-to-secukinumab.

The fact that patients in the original placebo group who received 3 mg IV doses without 6-mg loading doses achieved ACR response rates similar to those who took secukinumab during the whole trial “could suggest that the IV loading dose may not be required. This would need to be explored in a randomized head-to-head study, but it’s an interesting observation that may reduce costs and exposure to higher doses of medication at the start of treatment,” Dr. Goodson said.

Among the patients who received secukinumab at any point in the study, 63% had a treatment-emergent adverse event, including 5.9% with serious events. One death was reported in the placebo group before week 16. No other deaths were reported.
 

AxSpA trial details

In the axSpA trial, called INVIGORATE-1, researchers recruited people aged ≥18 years with a diagnosis of active radiographic axSpA according to modified New York criteria or nonradiographic axSpA according to ASAS criteria, and all had inflammatory back pain for ≥6 months with an onset before age 45. They were randomized at a 1:1 ratio to receive IV secukinumab (6 mg/kg loading dose, followed by 3 mg/kg every 4 weeks) or placebo for 16 weeks. At that point, the placebo group switched to the same monthly doses of IV secukinumab.

Participants had a mean age of about 39, and about one-third were female.

Following the statistical superiority in ASAS 40 response rates seen with IV secukinumab at week 16, patients who from there switched from placebo to IV secukinumab achieved comparable ASAS 40 response rates to those of patients originally randomized to secukinumab by week 24, reaching 66.8% for those on secukinumab the whole time and 74.9% for those who switched.

Secondary outcome measures were similar in both groups at week 52.

Among all patients who took secukinumab – the percentage with any adverse event was 63.2%, and 6% had a nonfatal adverse event deemed serious. There was one death during secukinumab treatment not suspected to be related to treatment.

In a presentation about the axSpA study findings, Atul Deodhar, MD, of Oregon Health & Science University, noted that “having an IV biologic available in the U.S. has some advantages. There are certain insurance providers such as Medicare where it is more economical for the patient to have an IV drug available.”

Dr. Deodhar also noted that in October the FDA approved a recommended lower dose for the IV treatment than in the study: 1.75 mg/kg instead of 3 mg/kg following the loading dose. That’s because the 3 mg/kg dose caused blood levels to be higher than those in the subcutaneous form, he said.

The FDA made the same dose recommendation for PsA.
 

Study limitations

Dr. Goodson, the U.K. consultant rheumatologist, noted a limitation of the trials: “It would have been interesting to compare IV to subcutaneous route secukinumab.” Still, the findings suggest that “the safety and efficacy of IV administration appears comparable,” she said.

“IV administration will have associated costs of attending hospital or infusion clinics,” she added, “and the cost of additional staff and administration need to be considered.”

Novartis, the maker of secukinumab, funded both studies. The PsA study authors report multiple relationships with industry, and some, such as Dr. Kivitz, have connections to Novartis. The axSpA study authors also report multiple relationships with industry, and some, such as Dr. Deodhar, have connections to Novartis. Some authors of both studies are Novartis employees. Dr. Goodson disclosed financial relationships with UCB and AbbVie.

SAN DIEGO – Monthly use of intravenously administered secukinumab (Cosentyx) proved its efficacy over placebo in treating psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA) in two industry-sponsored, randomized, double-blinded, phase 3 trials of the drug’s second and newly approved route of administration.

The studies of the human monoclonal antibody secukinumab, an interleukin-17 inhibitor, were presented at the annual meeting of the American College of Rheumatology. A subcutaneously injectable formulation of the drug is available, and the Food and Drug Administration approved the IV form for the conditions in October, although at a recommended lower monthly dose than the new trials examined.

In the PsA trial, 191 patients took IV secukinumab, and 190 took placebo. For the primary endpoint, the percentages who reached at least a 50% improvement in American College of Rheumatology response criteria (ACR 50) at 16 weeks were 31.4% and 6.3%, respectively (P < .0001).

In the axSpA trial, 264 patients took IV secukinumab, and 262 took placebo. The primary endpoint, at least a 40% improvement in Assessment of the Spondyloarthritis International Society response criteria (ASAS 40), was met at 16 weeks by 40.9% and 22.9%, respectively (P < .0001).

“Both studies appear to present clear efficacy of IV route administration of secukinumab with no clear increase in safety signals,” consultant rheumatologist Nicola Goodson, MBChB, PhD, of Aintree University Hospital in Liverpool, England, said in an interview.

“Offering IV administration as an option to patients is helpful,” added Dr. Goodson, who was not involved with the study but is familiar with its findings.

As Dr. Goodson explained, secukinumab “was the first IL [interleukin]-17 inhibitor used to treat spondyloarthropathies, and we have been using subcutaneous secukinumab to treat psoriasis, psoriatic arthritis, and axial spondyloarthritis/ankylosing spondylitis since 2016 in the U.K. Our experience with this medication has been good with similar efficacy to anti-TNF [tumor necrosis factor] therapy in axial spondyloarthritis. The medication is generally well-tolerated, and the subcutaneous pen injection device is easy for patients to use.”

However, IV treatment may speed up onset of action, she said, and it may be useful in situations when compliance is a challenge.
 

PsA trial details

In the PsA trial, known as INVIGORATE-2, researchers recruited patients who met the CASPAR criteria for active PsA with symptoms for ≥ 6 months, and had ≥ 3 tender joints out of 78 joints and ≥ 3 swollen joints out of 76.

Participants with a mean age of 48, including 55% females, were randomized 1:1 to receive placebo or secukinumab (6 mg/kg at baseline followed by 3 mg/kg every 4 weeks). Those in the placebo group were switched to the same monthly doses of secukinumab at 16 weeks.

“Patients who switched from the placebo had a similar increase of efficacy as the original treated group,” rheumatologist Alan J. Kivitz, MD, of the Altoona Center for Clinical Research, in Duncansville, Penn., said in his presentation at the meeting. Specifically, at 52 weeks, the groups had similar ACR 50 response rates: 58% with secukinumab and 64% with placebo-to-secukinumab.

The fact that patients in the original placebo group who received 3 mg IV doses without 6-mg loading doses achieved ACR response rates similar to those who took secukinumab during the whole trial “could suggest that the IV loading dose may not be required. This would need to be explored in a randomized head-to-head study, but it’s an interesting observation that may reduce costs and exposure to higher doses of medication at the start of treatment,” Dr. Goodson said.

Among the patients who received secukinumab at any point in the study, 63% had a treatment-emergent adverse event, including 5.9% with serious events. One death was reported in the placebo group before week 16. No other deaths were reported.
 

AxSpA trial details

In the axSpA trial, called INVIGORATE-1, researchers recruited people aged ≥18 years with a diagnosis of active radiographic axSpA according to modified New York criteria or nonradiographic axSpA according to ASAS criteria, and all had inflammatory back pain for ≥6 months with an onset before age 45. They were randomized at a 1:1 ratio to receive IV secukinumab (6 mg/kg loading dose, followed by 3 mg/kg every 4 weeks) or placebo for 16 weeks. At that point, the placebo group switched to the same monthly doses of IV secukinumab.

Participants had a mean age of about 39, and about one-third were female.

Following the statistical superiority in ASAS 40 response rates seen with IV secukinumab at week 16, patients who from there switched from placebo to IV secukinumab achieved comparable ASAS 40 response rates to those of patients originally randomized to secukinumab by week 24, reaching 66.8% for those on secukinumab the whole time and 74.9% for those who switched.

Secondary outcome measures were similar in both groups at week 52.

Among all patients who took secukinumab – the percentage with any adverse event was 63.2%, and 6% had a nonfatal adverse event deemed serious. There was one death during secukinumab treatment not suspected to be related to treatment.

In a presentation about the axSpA study findings, Atul Deodhar, MD, of Oregon Health & Science University, noted that “having an IV biologic available in the U.S. has some advantages. There are certain insurance providers such as Medicare where it is more economical for the patient to have an IV drug available.”

Dr. Deodhar also noted that in October the FDA approved a recommended lower dose for the IV treatment than in the study: 1.75 mg/kg instead of 3 mg/kg following the loading dose. That’s because the 3 mg/kg dose caused blood levels to be higher than those in the subcutaneous form, he said.

The FDA made the same dose recommendation for PsA.
 

Study limitations

Dr. Goodson, the U.K. consultant rheumatologist, noted a limitation of the trials: “It would have been interesting to compare IV to subcutaneous route secukinumab.” Still, the findings suggest that “the safety and efficacy of IV administration appears comparable,” she said.

“IV administration will have associated costs of attending hospital or infusion clinics,” she added, “and the cost of additional staff and administration need to be considered.”

Novartis, the maker of secukinumab, funded both studies. The PsA study authors report multiple relationships with industry, and some, such as Dr. Kivitz, have connections to Novartis. The axSpA study authors also report multiple relationships with industry, and some, such as Dr. Deodhar, have connections to Novartis. Some authors of both studies are Novartis employees. Dr. Goodson disclosed financial relationships with UCB and AbbVie.