Spondyloarthropathies

MIAMI – Diabetes mellitus, hypothyroidism, Cushing’s disease, and osteoporosis occur more frequently in people with psoriatic arthritis than in controls, a large cohort study reveals. Prevalence of these endocrine conditions was greater in a group of 3,161 patients with psoriatic arthritis, compared with 31,610 matched controls.

“We recommend that physicians should be aware of comorbid associations to provide comprehensive medical care to patients with psoriatic arthritis,” said Amir Haddad, MD, of the department of rheumatology at Carmel Medical Center in Haifa, Israel.

Dr. Haddad and his colleagues, however, found no significant differences in the prevalence of hyperthyroidism, hypo- and hyperparathyroidism, hyperprolactinemia, Addison’s disease, diabetes insipidus, pituitary adenoma, or acromegaly between groups in this retrospective, cross-sectional study.

They identified 1,474 men and 1,687 women diagnosed with psoriatic disease from 2000 to 2013 using the Clalit health services database in Israel. This group was a mean of 58 years old and 53% were women. Each patient was matched with 10 age- and gender-matched controls without psoriatic disease for the study.

“This is, to our knowledge, one of the largest real-life cohorts of psoriatic patient registries,” Dr. Haddad said at the annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA).

In the psoriatic arthritis group versus controls, diabetes mellitus prevalence was 27.9% vs. 20.7%; for hypothyroidism it was 12.7% vs. 8.6%; and for Cushing’s disease it was 0.3% vs. 0.1%. All these differences were statically significant (P less than 0.0001). Osteoporosis prevalence also differed significantly between the psoriatic arthritis and control groups: 13.2% vs. 9.1% (P less than 0.001).

Greater awareness of nonskin and nonjoint comorbidities is important, Dr. Haddad said, because it can influence choice of therapy and management of patients with psoriatic arthritis.

The investigators also conducted univariate and multivariate regression analyses. Compared with controls, the results suggest psoriatic arthritis patients have a higher risk for diabetes mellitus (odds ratio, 1.48), hypothyroidism (OR, 1.56), and osteoporosis (OR, 1.52). The risk for Cushing’s disease was notably higher (OR, 5.31) in the univariate analysis.

Risks for these endocrine conditions remained higher for the psoriatic arthritis patients in a multivariate regression analysis as well. For example, risk for diabetes mellitus (OR, 1.30) remained after adjusting for age, gender, smoking, obesity, and steroid use. Risk of hypothyroidism (OR, 1.61) remained after adjusting for age and gender; risk of osteoporosis (OR, 1.50) after adjusting for age, gender, steroid use, and smoking; and risk of Cushing’s disease (OR, 3.79) after adjustment for age, gender, and steroid use.

The large, population-based cohort is a strength of the study. “We are now going back to see how many of these patients were seen by rheumatologists,” Dr. Haddad said. A lack of association with disease burden is a potential limitation, he added.

Thirty percent of patients were treated with biologics and about 67% with steroids. “That number treated with steroids seems high,” a meeting attendee commented. Dr. Haddad explained that it is the percentage ever treated with steroids, not necessarily currently on steroids.

In a separate session at the GRAPPA meeting addressing psoriatic disease treatment recommendations, an attendee asked about specific recommendations for comorbidities. For now, GRAPPA plans to include comorbidities within its overall recommendations, as it did in its most recent update, released in January 2016. A limited amount of data is a primary reason.

“As the evidence on comorbidities gets better, we may someday have separate recommendations for comorbidities,” said Laura Coates, MD, a clinical lecturer in rheumatology at the University of Leeds (England).

“The comorbidities are very important,” said Arthur F. Kavanaugh, MD, professor of medicine at the University of California, San Diego. “That’s trickier and deals with the international nature of GRAPPA. It’s hard to say, ‘Go see this specialist,’ because that might not be standard of care in that country.”

Dr. Haddad, Dr. Coates, and Dr. Kavanaugh reported having no relevant financial disclosures.

MIAMI – Diabetes mellitus, hypothyroidism, Cushing’s disease, and osteoporosis occur more frequently in people with psoriatic arthritis than in controls, a large cohort study reveals. Prevalence of these endocrine conditions was greater in a group of 3,161 patients with psoriatic arthritis, compared with 31,610 matched controls.

“We recommend that physicians should be aware of comorbid associations to provide comprehensive medical care to patients with psoriatic arthritis,” said Amir Haddad, MD, of the department of rheumatology at Carmel Medical Center in Haifa, Israel.

Dr. Haddad and his colleagues, however, found no significant differences in the prevalence of hyperthyroidism, hypo- and hyperparathyroidism, hyperprolactinemia, Addison’s disease, diabetes insipidus, pituitary adenoma, or acromegaly between groups in this retrospective, cross-sectional study.

They identified 1,474 men and 1,687 women diagnosed with psoriatic disease from 2000 to 2013 using the Clalit health services database in Israel. This group was a mean of 58 years old and 53% were women. Each patient was matched with 10 age- and gender-matched controls without psoriatic disease for the study.

“This is, to our knowledge, one of the largest real-life cohorts of psoriatic patient registries,” Dr. Haddad said at the annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA).

In the psoriatic arthritis group versus controls, diabetes mellitus prevalence was 27.9% vs. 20.7%; for hypothyroidism it was 12.7% vs. 8.6%; and for Cushing’s disease it was 0.3% vs. 0.1%. All these differences were statically significant (P less than 0.0001). Osteoporosis prevalence also differed significantly between the psoriatic arthritis and control groups: 13.2% vs. 9.1% (P less than 0.001).

Greater awareness of nonskin and nonjoint comorbidities is important, Dr. Haddad said, because it can influence choice of therapy and management of patients with psoriatic arthritis.

The investigators also conducted univariate and multivariate regression analyses. Compared with controls, the results suggest psoriatic arthritis patients have a higher risk for diabetes mellitus (odds ratio, 1.48), hypothyroidism (OR, 1.56), and osteoporosis (OR, 1.52). The risk for Cushing’s disease was notably higher (OR, 5.31) in the univariate analysis.

Risks for these endocrine conditions remained higher for the psoriatic arthritis patients in a multivariate regression analysis as well. For example, risk for diabetes mellitus (OR, 1.30) remained after adjusting for age, gender, smoking, obesity, and steroid use. Risk of hypothyroidism (OR, 1.61) remained after adjusting for age and gender; risk of osteoporosis (OR, 1.50) after adjusting for age, gender, steroid use, and smoking; and risk of Cushing’s disease (OR, 3.79) after adjustment for age, gender, and steroid use.

The large, population-based cohort is a strength of the study. “We are now going back to see how many of these patients were seen by rheumatologists,” Dr. Haddad said. A lack of association with disease burden is a potential limitation, he added.

Thirty percent of patients were treated with biologics and about 67% with steroids. “That number treated with steroids seems high,” a meeting attendee commented. Dr. Haddad explained that it is the percentage ever treated with steroids, not necessarily currently on steroids.

In a separate session at the GRAPPA meeting addressing psoriatic disease treatment recommendations, an attendee asked about specific recommendations for comorbidities. For now, GRAPPA plans to include comorbidities within its overall recommendations, as it did in its most recent update, released in January 2016. A limited amount of data is a primary reason.

“As the evidence on comorbidities gets better, we may someday have separate recommendations for comorbidities,” said Laura Coates, MD, a clinical lecturer in rheumatology at the University of Leeds (England).

“The comorbidities are very important,” said Arthur F. Kavanaugh, MD, professor of medicine at the University of California, San Diego. “That’s trickier and deals with the international nature of GRAPPA. It’s hard to say, ‘Go see this specialist,’ because that might not be standard of care in that country.”

Dr. Haddad, Dr. Coates, and Dr. Kavanaugh reported having no relevant financial disclosures.

MIAMI – Diabetes mellitus, hypothyroidism, Cushing’s disease, and osteoporosis occur more frequently in people with psoriatic arthritis than in controls, a large cohort study reveals. Prevalence of these endocrine conditions was greater in a group of 3,161 patients with psoriatic arthritis, compared with 31,610 matched controls.

“We recommend that physicians should be aware of comorbid associations to provide comprehensive medical care to patients with psoriatic arthritis,” said Amir Haddad, MD, of the department of rheumatology at Carmel Medical Center in Haifa, Israel.

Dr. Haddad and his colleagues, however, found no significant differences in the prevalence of hyperthyroidism, hypo- and hyperparathyroidism, hyperprolactinemia, Addison’s disease, diabetes insipidus, pituitary adenoma, or acromegaly between groups in this retrospective, cross-sectional study.

They identified 1,474 men and 1,687 women diagnosed with psoriatic disease from 2000 to 2013 using the Clalit health services database in Israel. This group was a mean of 58 years old and 53% were women. Each patient was matched with 10 age- and gender-matched controls without psoriatic disease for the study.

“This is, to our knowledge, one of the largest real-life cohorts of psoriatic patient registries,” Dr. Haddad said at the annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA).

In the psoriatic arthritis group versus controls, diabetes mellitus prevalence was 27.9% vs. 20.7%; for hypothyroidism it was 12.7% vs. 8.6%; and for Cushing’s disease it was 0.3% vs. 0.1%. All these differences were statically significant (P less than 0.0001). Osteoporosis prevalence also differed significantly between the psoriatic arthritis and control groups: 13.2% vs. 9.1% (P less than 0.001).

Greater awareness of nonskin and nonjoint comorbidities is important, Dr. Haddad said, because it can influence choice of therapy and management of patients with psoriatic arthritis.

The investigators also conducted univariate and multivariate regression analyses. Compared with controls, the results suggest psoriatic arthritis patients have a higher risk for diabetes mellitus (odds ratio, 1.48), hypothyroidism (OR, 1.56), and osteoporosis (OR, 1.52). The risk for Cushing’s disease was notably higher (OR, 5.31) in the univariate analysis.

Risks for these endocrine conditions remained higher for the psoriatic arthritis patients in a multivariate regression analysis as well. For example, risk for diabetes mellitus (OR, 1.30) remained after adjusting for age, gender, smoking, obesity, and steroid use. Risk of hypothyroidism (OR, 1.61) remained after adjusting for age and gender; risk of osteoporosis (OR, 1.50) after adjusting for age, gender, steroid use, and smoking; and risk of Cushing’s disease (OR, 3.79) after adjustment for age, gender, and steroid use.

The large, population-based cohort is a strength of the study. “We are now going back to see how many of these patients were seen by rheumatologists,” Dr. Haddad said. A lack of association with disease burden is a potential limitation, he added.

Thirty percent of patients were treated with biologics and about 67% with steroids. “That number treated with steroids seems high,” a meeting attendee commented. Dr. Haddad explained that it is the percentage ever treated with steroids, not necessarily currently on steroids.

In a separate session at the GRAPPA meeting addressing psoriatic disease treatment recommendations, an attendee asked about specific recommendations for comorbidities. For now, GRAPPA plans to include comorbidities within its overall recommendations, as it did in its most recent update, released in January 2016. A limited amount of data is a primary reason.

“As the evidence on comorbidities gets better, we may someday have separate recommendations for comorbidities,” said Laura Coates, MD, a clinical lecturer in rheumatology at the University of Leeds (England).

“The comorbidities are very important,” said Arthur F. Kavanaugh, MD, professor of medicine at the University of California, San Diego. “That’s trickier and deals with the international nature of GRAPPA. It’s hard to say, ‘Go see this specialist,’ because that might not be standard of care in that country.”

Dr. Haddad, Dr. Coates, and Dr. Kavanaugh reported having no relevant financial disclosures.

DENVER – Weight loss enhances responsiveness of patients with psoriatic arthritis to tumor necrosis factor inhibitors and should be part of routine care when using these drugs in this setting, Lianne Gensler, MD, said at an educational symposium organized by the Spondyloarthritis Research and Treatment Network.

She cited results from a randomized study conducted in Naples, Italy, with 138 patients and published in 2014, which showed the greater the weight loss of patients with psoriatic arthritis (PsA) during their first 6 months on treatment with a tumor necrosis factor (TNF) inhibitor, the greater their rate of achieving minimal disease activity by the end of the first 6 months.

Patients achieving a 5%-10% weight loss in the first 6 months on TNF-inhibitor treatment had a nearly fourfold increased rate of minimally active disease, compared with patients who had anything less than a 5% weight loss (including patients who may have had no weight change or gained weight). Those who lost more than 10% of their starting weight had a nearly sevenfold higher rate of achieving minimal disease activity, compared with those who had anything less than a 5% weight loss (Ann Rheum Dis. 2014 June;73[6]:1157-62).

“I use this result in my routine practice when starting patients on a TNF inhibitor or when patients are not responding to TNF-inhibitor treatment,” said Dr. Gensler, director of the ankylosing spondylitis clinic at the University of California, San Francisco.

“It’s a patient-centered approach to improving outcomes,” she said at the symposium, also organized by the Group for the Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA).

The 2015 guidelines (Arthritis Rheum. 2016 May;68[5]:1060-71) for managing psoriasis and PsA from GRAPPA cite the Naples data to recommend that all PsA patients be encouraged to achieve and maintain a healthy body weight, she noted.

The evidence that weight can affect TNF-inhibitor response in PsA patients first dates to a prior report from the same Naples group, which prospectively followed 270 PsA patients starting a TNF-inhibitor regimen, including 135 obese patients and 135 at normal weight. After 12 months, 36% of patients had minimal disease activity. The obese patients were nearly fivefold more likely to not achieve minimal disease activity during the first 12 months on treatment, compared with the normal-weight patients (Arthritis Care Res. 2013 Jan;65[1]:141-7). Obesity also was linked with a significantly increased risk that patients who achieved minimal disease activity after 1 year would relapse by 2-year follow-up.

“These studies have provided a new reason for [PsA] patients to lose weight,” agreed Atul A. Deodhar, MD, professor of medicine and medical director of the rheumatology clinics at the Oregon Health and Science University in Portland. “Before we counseled patients to lose weight for other reasons. Now there is a rheumatologic reason.”

Smoking cessation is another lifestyle step recently shown to improve TNF-inhibitor response in PsA patients, Dr. Deodhar added. For example, results from a recent Danish study of 1,388 PsA patients enrolled in the Danish national registry showed that smokers had significantly worse responses, compared with nonsmokers, during their first 6 months on a TNF-inhibitor regimen (Ann Rheum Dis. 2015 Dec;74[12]:2130-6).

Both weight loss and smoking cessation “have a powerful effect. I use these results in my practice to counsel patients to stop smoking and lose weight [for] those going on a TNF inhibitor, or when a TNF inhibitor is not working,” Dr. Deodhar said in an interview.

[email protected]

On Twitter @mitchelzoler

DENVER – Weight loss enhances responsiveness of patients with psoriatic arthritis to tumor necrosis factor inhibitors and should be part of routine care when using these drugs in this setting, Lianne Gensler, MD, said at an educational symposium organized by the Spondyloarthritis Research and Treatment Network.

She cited results from a randomized study conducted in Naples, Italy, with 138 patients and published in 2014, which showed the greater the weight loss of patients with psoriatic arthritis (PsA) during their first 6 months on treatment with a tumor necrosis factor (TNF) inhibitor, the greater their rate of achieving minimal disease activity by the end of the first 6 months.

Patients achieving a 5%-10% weight loss in the first 6 months on TNF-inhibitor treatment had a nearly fourfold increased rate of minimally active disease, compared with patients who had anything less than a 5% weight loss (including patients who may have had no weight change or gained weight). Those who lost more than 10% of their starting weight had a nearly sevenfold higher rate of achieving minimal disease activity, compared with those who had anything less than a 5% weight loss (Ann Rheum Dis. 2014 June;73[6]:1157-62).

“I use this result in my routine practice when starting patients on a TNF inhibitor or when patients are not responding to TNF-inhibitor treatment,” said Dr. Gensler, director of the ankylosing spondylitis clinic at the University of California, San Francisco.

“It’s a patient-centered approach to improving outcomes,” she said at the symposium, also organized by the Group for the Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA).

The 2015 guidelines (Arthritis Rheum. 2016 May;68[5]:1060-71) for managing psoriasis and PsA from GRAPPA cite the Naples data to recommend that all PsA patients be encouraged to achieve and maintain a healthy body weight, she noted.

The evidence that weight can affect TNF-inhibitor response in PsA patients first dates to a prior report from the same Naples group, which prospectively followed 270 PsA patients starting a TNF-inhibitor regimen, including 135 obese patients and 135 at normal weight. After 12 months, 36% of patients had minimal disease activity. The obese patients were nearly fivefold more likely to not achieve minimal disease activity during the first 12 months on treatment, compared with the normal-weight patients (Arthritis Care Res. 2013 Jan;65[1]:141-7). Obesity also was linked with a significantly increased risk that patients who achieved minimal disease activity after 1 year would relapse by 2-year follow-up.

“These studies have provided a new reason for [PsA] patients to lose weight,” agreed Atul A. Deodhar, MD, professor of medicine and medical director of the rheumatology clinics at the Oregon Health and Science University in Portland. “Before we counseled patients to lose weight for other reasons. Now there is a rheumatologic reason.”

Smoking cessation is another lifestyle step recently shown to improve TNF-inhibitor response in PsA patients, Dr. Deodhar added. For example, results from a recent Danish study of 1,388 PsA patients enrolled in the Danish national registry showed that smokers had significantly worse responses, compared with nonsmokers, during their first 6 months on a TNF-inhibitor regimen (Ann Rheum Dis. 2015 Dec;74[12]:2130-6).

Both weight loss and smoking cessation “have a powerful effect. I use these results in my practice to counsel patients to stop smoking and lose weight [for] those going on a TNF inhibitor, or when a TNF inhibitor is not working,” Dr. Deodhar said in an interview.

[email protected]

On Twitter @mitchelzoler

DENVER – Weight loss enhances responsiveness of patients with psoriatic arthritis to tumor necrosis factor inhibitors and should be part of routine care when using these drugs in this setting, Lianne Gensler, MD, said at an educational symposium organized by the Spondyloarthritis Research and Treatment Network.

She cited results from a randomized study conducted in Naples, Italy, with 138 patients and published in 2014, which showed the greater the weight loss of patients with psoriatic arthritis (PsA) during their first 6 months on treatment with a tumor necrosis factor (TNF) inhibitor, the greater their rate of achieving minimal disease activity by the end of the first 6 months.

Patients achieving a 5%-10% weight loss in the first 6 months on TNF-inhibitor treatment had a nearly fourfold increased rate of minimally active disease, compared with patients who had anything less than a 5% weight loss (including patients who may have had no weight change or gained weight). Those who lost more than 10% of their starting weight had a nearly sevenfold higher rate of achieving minimal disease activity, compared with those who had anything less than a 5% weight loss (Ann Rheum Dis. 2014 June;73[6]:1157-62).

“I use this result in my routine practice when starting patients on a TNF inhibitor or when patients are not responding to TNF-inhibitor treatment,” said Dr. Gensler, director of the ankylosing spondylitis clinic at the University of California, San Francisco.

“It’s a patient-centered approach to improving outcomes,” she said at the symposium, also organized by the Group for the Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA).

The 2015 guidelines (Arthritis Rheum. 2016 May;68[5]:1060-71) for managing psoriasis and PsA from GRAPPA cite the Naples data to recommend that all PsA patients be encouraged to achieve and maintain a healthy body weight, she noted.

The evidence that weight can affect TNF-inhibitor response in PsA patients first dates to a prior report from the same Naples group, which prospectively followed 270 PsA patients starting a TNF-inhibitor regimen, including 135 obese patients and 135 at normal weight. After 12 months, 36% of patients had minimal disease activity. The obese patients were nearly fivefold more likely to not achieve minimal disease activity during the first 12 months on treatment, compared with the normal-weight patients (Arthritis Care Res. 2013 Jan;65[1]:141-7). Obesity also was linked with a significantly increased risk that patients who achieved minimal disease activity after 1 year would relapse by 2-year follow-up.

“These studies have provided a new reason for [PsA] patients to lose weight,” agreed Atul A. Deodhar, MD, professor of medicine and medical director of the rheumatology clinics at the Oregon Health and Science University in Portland. “Before we counseled patients to lose weight for other reasons. Now there is a rheumatologic reason.”

Smoking cessation is another lifestyle step recently shown to improve TNF-inhibitor response in PsA patients, Dr. Deodhar added. For example, results from a recent Danish study of 1,388 PsA patients enrolled in the Danish national registry showed that smokers had significantly worse responses, compared with nonsmokers, during their first 6 months on a TNF-inhibitor regimen (Ann Rheum Dis. 2015 Dec;74[12]:2130-6).

Both weight loss and smoking cessation “have a powerful effect. I use these results in my practice to counsel patients to stop smoking and lose weight [for] those going on a TNF inhibitor, or when a TNF inhibitor is not working,” Dr. Deodhar said in an interview.

[email protected]

On Twitter @mitchelzoler

MIAMI – Combined rheumatology-dermatology clinics to help people with psoriasis, psoriatic arthritis, and other relevant overlapping conditions continue to evolve, with evidence suggesting advantages and challenges for both patients and physicians.

Physicians like the improved communication and greater collaboration but still have reservations about billing and scheduling, according to preliminary results of a survey conducted by the Psoriasis and Psoriatic Arthritis Clinic Multicenter Advancement Network (PPACMAN). For patients, the advantages go beyond convenience, according to a 1-year study of outcomes at a Rhode Island Hospital–Brown University combined clinic in Providence.

“The goal of the combined clinics survey is to gauge strengths, barriers, and challenges to creating these models, to learn from one another to improve current clinical care, and to support propagation of these models,” said Joseph F. Merola, MD, at the annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis.

Multiple clinic models

The clinic setups differ. In those settings where rheumatologists and dermatologists see patients on the same day, approximately three-quarters provide care together in the same room. The remaining clinics see patients through serial visits. Another 30% of respondents said dermatologists and rheumatologists generally see patients in a combined clinic on different days.

Jay Omobono

“Rheumatologists said it is a satisfying and rewarding endeavor, they form closer ties with colleagues, and it allows early, improved communication,” said Dr. Merola, a rheumatologist and dermatologist who is co-director of the Center for Skin and Related Musculoskeletal Diseases, a combined clinic at Brigham and Women’s Hospital in Boston.

Some common benefits, each cited by more than 80% of respondents, include a prompt and accurate diagnosis of psoriatic arthritis, the ability of physicians to learn from each other, and multiple training opportunities for residents and fellows. In fact, 72% said their combined clinic has rheumatology fellows, 82% have dermatology residents, and 27% incorporate internal medicine trainees.

Other than rheumatologists and dermatologists, 31% said their clinic has dedicated nursing, 15% have a cardiologist, and 15% have a psychiatrist.

A majority of physicians (92%) said they bill through their own department. At a subsequent roundtable discussion, Dr. Merola noted that patients pay separate copays at the combined clinic. “We’ve had some complaints from patients. They don’t like having two copayments.”

“You have to tell patients in advance,” suggested Soumya M. Reddy, MD, a rheumatologist at NYU Langone Medical Center in New York and co-director of its Psoriasis and Psoriatic Arthritis Center.

Common conditions and challenges

Not surprisingly, psoriasis and psoriatic arthritis are the most common conditions treated in these clinics, followed by lupus and dermatomyositis. Most clinics see patients either once weekly or once monthly.

A major concern expressed by 75% surrounds scheduling. More than half, 58%, worry about demonstrating value to their institution. Only a minority, 17%, responded that achieving consensus on patient management is a challenge.

In general, rheumatology evaluations take more time than dermatology assessments, presenting a challenge for scheduling and maximizing physician time. “You don’t really want the dermatologist sitting there for 20 minutes not really doing a lot,” said Alison Ehrlich, MD, professor and chair of dermatology at George Washington University in Washington.

The solution at Brigham and Women’s Hospital is to staff the clinic with two dermatologists and one rheumatologist. The two dermatologists see about 20 patients each in a half-day; the rheumatologist probably treats about 6 to 8 of those 40 patients, Dr. Merola said. At George Washington, Dr. Ehrlich sees patients along with the rheumatologist, leaves the room to treat other patients, later consults with her colleague, and they go back in together as necessary.

“The patients are incredibly appreciative” of the combined clinic, Dr. Ehrlich said. “They really love it.”

The survey is ongoing. The preliminary responses above are based on 17 responses, a 52% response rate. Of the respondents, 10 are dermatologists, 6 are rheumatologists, and 1 is dual trained. Since the meeting, Dr. Merola indicated that another two dermatologists and three rheumatologists have responded to the survey.

The Brown University experience

Charis Gn, MD, and colleagues studied outcomes for 167 patients treated at a combined clinic at Rhode Island Hospital. The ultimate goal of the clinic is “to identify patients with psoriatic arthritis early on,” Dr. Gn said at a poster presentation at the GRAPPA annual meeting. “We wanted to see what kind of outcomes [we get] for patients who see rheumatology and dermatology.”

About one-third of patients left the clinic with changes in diagnosis. About 1 in 5 patients with psoriasis were diagnosed with psoriatic arthritis as well. For the psoriasis patients newly diagnosed with psoriatic arthritis, 80% had an escalation in treatment, said Dr. Gn, an internal medicine resident.

Of the 41 patients with psoriasis, 17 (41%) had a treatment escalation. The same was true for 15 (79%) of the 19 patients with psoriatic arthritis post-evaluation.

Regarding the combined clinic, “it’s shown to be very beneficial for patients with psoriatic arthritis,” Dr. Gn said.

The record review from July 2014 to February 2016 shows the clinic also serves patients with cutaneous lupus, dermatomyositis, pyoderma gangrenosum, vasculitis, and rheumatoid arthritis, among others.

The presenters had no relevant disclosures.

MIAMI – Combined rheumatology-dermatology clinics to help people with psoriasis, psoriatic arthritis, and other relevant overlapping conditions continue to evolve, with evidence suggesting advantages and challenges for both patients and physicians.

Physicians like the improved communication and greater collaboration but still have reservations about billing and scheduling, according to preliminary results of a survey conducted by the Psoriasis and Psoriatic Arthritis Clinic Multicenter Advancement Network (PPACMAN). For patients, the advantages go beyond convenience, according to a 1-year study of outcomes at a Rhode Island Hospital–Brown University combined clinic in Providence.

“The goal of the combined clinics survey is to gauge strengths, barriers, and challenges to creating these models, to learn from one another to improve current clinical care, and to support propagation of these models,” said Joseph F. Merola, MD, at the annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis.

Multiple clinic models

The clinic setups differ. In those settings where rheumatologists and dermatologists see patients on the same day, approximately three-quarters provide care together in the same room. The remaining clinics see patients through serial visits. Another 30% of respondents said dermatologists and rheumatologists generally see patients in a combined clinic on different days.

Jay Omobono

“Rheumatologists said it is a satisfying and rewarding endeavor, they form closer ties with colleagues, and it allows early, improved communication,” said Dr. Merola, a rheumatologist and dermatologist who is co-director of the Center for Skin and Related Musculoskeletal Diseases, a combined clinic at Brigham and Women’s Hospital in Boston.

Some common benefits, each cited by more than 80% of respondents, include a prompt and accurate diagnosis of psoriatic arthritis, the ability of physicians to learn from each other, and multiple training opportunities for residents and fellows. In fact, 72% said their combined clinic has rheumatology fellows, 82% have dermatology residents, and 27% incorporate internal medicine trainees.

Other than rheumatologists and dermatologists, 31% said their clinic has dedicated nursing, 15% have a cardiologist, and 15% have a psychiatrist.

A majority of physicians (92%) said they bill through their own department. At a subsequent roundtable discussion, Dr. Merola noted that patients pay separate copays at the combined clinic. “We’ve had some complaints from patients. They don’t like having two copayments.”

“You have to tell patients in advance,” suggested Soumya M. Reddy, MD, a rheumatologist at NYU Langone Medical Center in New York and co-director of its Psoriasis and Psoriatic Arthritis Center.

Common conditions and challenges

Not surprisingly, psoriasis and psoriatic arthritis are the most common conditions treated in these clinics, followed by lupus and dermatomyositis. Most clinics see patients either once weekly or once monthly.

A major concern expressed by 75% surrounds scheduling. More than half, 58%, worry about demonstrating value to their institution. Only a minority, 17%, responded that achieving consensus on patient management is a challenge.

In general, rheumatology evaluations take more time than dermatology assessments, presenting a challenge for scheduling and maximizing physician time. “You don’t really want the dermatologist sitting there for 20 minutes not really doing a lot,” said Alison Ehrlich, MD, professor and chair of dermatology at George Washington University in Washington.

The solution at Brigham and Women’s Hospital is to staff the clinic with two dermatologists and one rheumatologist. The two dermatologists see about 20 patients each in a half-day; the rheumatologist probably treats about 6 to 8 of those 40 patients, Dr. Merola said. At George Washington, Dr. Ehrlich sees patients along with the rheumatologist, leaves the room to treat other patients, later consults with her colleague, and they go back in together as necessary.

“The patients are incredibly appreciative” of the combined clinic, Dr. Ehrlich said. “They really love it.”

The survey is ongoing. The preliminary responses above are based on 17 responses, a 52% response rate. Of the respondents, 10 are dermatologists, 6 are rheumatologists, and 1 is dual trained. Since the meeting, Dr. Merola indicated that another two dermatologists and three rheumatologists have responded to the survey.

The Brown University experience

Charis Gn, MD, and colleagues studied outcomes for 167 patients treated at a combined clinic at Rhode Island Hospital. The ultimate goal of the clinic is “to identify patients with psoriatic arthritis early on,” Dr. Gn said at a poster presentation at the GRAPPA annual meeting. “We wanted to see what kind of outcomes [we get] for patients who see rheumatology and dermatology.”

About one-third of patients left the clinic with changes in diagnosis. About 1 in 5 patients with psoriasis were diagnosed with psoriatic arthritis as well. For the psoriasis patients newly diagnosed with psoriatic arthritis, 80% had an escalation in treatment, said Dr. Gn, an internal medicine resident.

Of the 41 patients with psoriasis, 17 (41%) had a treatment escalation. The same was true for 15 (79%) of the 19 patients with psoriatic arthritis post-evaluation.

Regarding the combined clinic, “it’s shown to be very beneficial for patients with psoriatic arthritis,” Dr. Gn said.

The record review from July 2014 to February 2016 shows the clinic also serves patients with cutaneous lupus, dermatomyositis, pyoderma gangrenosum, vasculitis, and rheumatoid arthritis, among others.

The presenters had no relevant disclosures.

MIAMI – Combined rheumatology-dermatology clinics to help people with psoriasis, psoriatic arthritis, and other relevant overlapping conditions continue to evolve, with evidence suggesting advantages and challenges for both patients and physicians.

Physicians like the improved communication and greater collaboration but still have reservations about billing and scheduling, according to preliminary results of a survey conducted by the Psoriasis and Psoriatic Arthritis Clinic Multicenter Advancement Network (PPACMAN). For patients, the advantages go beyond convenience, according to a 1-year study of outcomes at a Rhode Island Hospital–Brown University combined clinic in Providence.

“The goal of the combined clinics survey is to gauge strengths, barriers, and challenges to creating these models, to learn from one another to improve current clinical care, and to support propagation of these models,” said Joseph F. Merola, MD, at the annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis.

Multiple clinic models

The clinic setups differ. In those settings where rheumatologists and dermatologists see patients on the same day, approximately three-quarters provide care together in the same room. The remaining clinics see patients through serial visits. Another 30% of respondents said dermatologists and rheumatologists generally see patients in a combined clinic on different days.

Jay Omobono

“Rheumatologists said it is a satisfying and rewarding endeavor, they form closer ties with colleagues, and it allows early, improved communication,” said Dr. Merola, a rheumatologist and dermatologist who is co-director of the Center for Skin and Related Musculoskeletal Diseases, a combined clinic at Brigham and Women’s Hospital in Boston.

Some common benefits, each cited by more than 80% of respondents, include a prompt and accurate diagnosis of psoriatic arthritis, the ability of physicians to learn from each other, and multiple training opportunities for residents and fellows. In fact, 72% said their combined clinic has rheumatology fellows, 82% have dermatology residents, and 27% incorporate internal medicine trainees.

Other than rheumatologists and dermatologists, 31% said their clinic has dedicated nursing, 15% have a cardiologist, and 15% have a psychiatrist.

A majority of physicians (92%) said they bill through their own department. At a subsequent roundtable discussion, Dr. Merola noted that patients pay separate copays at the combined clinic. “We’ve had some complaints from patients. They don’t like having two copayments.”

“You have to tell patients in advance,” suggested Soumya M. Reddy, MD, a rheumatologist at NYU Langone Medical Center in New York and co-director of its Psoriasis and Psoriatic Arthritis Center.

Common conditions and challenges

Not surprisingly, psoriasis and psoriatic arthritis are the most common conditions treated in these clinics, followed by lupus and dermatomyositis. Most clinics see patients either once weekly or once monthly.

A major concern expressed by 75% surrounds scheduling. More than half, 58%, worry about demonstrating value to their institution. Only a minority, 17%, responded that achieving consensus on patient management is a challenge.

In general, rheumatology evaluations take more time than dermatology assessments, presenting a challenge for scheduling and maximizing physician time. “You don’t really want the dermatologist sitting there for 20 minutes not really doing a lot,” said Alison Ehrlich, MD, professor and chair of dermatology at George Washington University in Washington.

The solution at Brigham and Women’s Hospital is to staff the clinic with two dermatologists and one rheumatologist. The two dermatologists see about 20 patients each in a half-day; the rheumatologist probably treats about 6 to 8 of those 40 patients, Dr. Merola said. At George Washington, Dr. Ehrlich sees patients along with the rheumatologist, leaves the room to treat other patients, later consults with her colleague, and they go back in together as necessary.

“The patients are incredibly appreciative” of the combined clinic, Dr. Ehrlich said. “They really love it.”

The survey is ongoing. The preliminary responses above are based on 17 responses, a 52% response rate. Of the respondents, 10 are dermatologists, 6 are rheumatologists, and 1 is dual trained. Since the meeting, Dr. Merola indicated that another two dermatologists and three rheumatologists have responded to the survey.

The Brown University experience

Charis Gn, MD, and colleagues studied outcomes for 167 patients treated at a combined clinic at Rhode Island Hospital. The ultimate goal of the clinic is “to identify patients with psoriatic arthritis early on,” Dr. Gn said at a poster presentation at the GRAPPA annual meeting. “We wanted to see what kind of outcomes [we get] for patients who see rheumatology and dermatology.”

About one-third of patients left the clinic with changes in diagnosis. About 1 in 5 patients with psoriasis were diagnosed with psoriatic arthritis as well. For the psoriasis patients newly diagnosed with psoriatic arthritis, 80% had an escalation in treatment, said Dr. Gn, an internal medicine resident.

Of the 41 patients with psoriasis, 17 (41%) had a treatment escalation. The same was true for 15 (79%) of the 19 patients with psoriatic arthritis post-evaluation.

Regarding the combined clinic, “it’s shown to be very beneficial for patients with psoriatic arthritis,” Dr. Gn said.

The record review from July 2014 to February 2016 shows the clinic also serves patients with cutaneous lupus, dermatomyositis, pyoderma gangrenosum, vasculitis, and rheumatoid arthritis, among others.

The presenters had no relevant disclosures.

MIAMI – Patients with psoriatic arthritis had a higher prevalence and greater extent of coronary artery plaque in a pilot study comparison with healthy control patients that may point to increased risk independent of traditional cardiovascular risk factors.

In the study, coronary artery plaque as assessed by cardiac computed tomography angiography (CCTA) occurred in 39 (78%) of 50 patients with psoriatic arthritis, a significantly higher rate than that observed for healthy controls (11 of 25, 44%).

©vizualis/thinkstockphotos.com

Investigators not only measured plaque volume, but also assessed the type of plaque: calcified, noncalcified, or mixed. Mixed plaque predominated. This could be important because “noncalcified and mixed carry higher risk for rupture and later cardiovascular events,” Agnes Szentpetery, MD, a research fellow at St. Vincent’s University Hospital in Dublin, said at the annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis.

She and her colleagues also found more clinically significant stenosis among the 50 participants with psoriatic arthritis, compared with 25 healthy controls matched for age, sex, smoking status, and presence of metabolic syndrome. “This pilot study is the first to assess coronary plaques in asymptomatic patients with psoriatic arthritis with CCTA,” Dr. Szentpetery said.

Total plaque volume was higher in the psoriatic arthritis group versus controls, and higher in the left main artery for psoriatic arthritis patients, both with and without metabolic syndrome.

The study points to increased risk independent of traditional cardiovascular risk factors. For example, CCTA revealed no difference in plaque volume between patients with and without metabolic disease. In addition, a previous study suggests “the burden of carotid artery plaques is higher in patients with psoriatic arthritis compared to those with psoriasis alone,” Dr. Szentpetery said, citing a cross-sectional study comparing 125 people with psoriasis to 114 others with psoriatic arthritis (Ann Rheum Dis. 2013 May;72[5]:715-20).

Perhaps not surprisingly, inflammation could be driving the association between psoriatic and cardiovascular disease risk. Other investigators suggest chronic, low-grade inflammation leads to atherosclerosis through a maladaptive immune response and altered lipid metabolism, for example (Nat Med. 2011 Nov;17[11]:1410-22).

In the current study, the patients with psoriatic arthritis had well-established disease, occurring for a mean duration of 19 years. Mean age was 58 years, and 54% were men. Approximately 60% were taking disease-modifying antirheumatic drugs, two-thirds were taking biologics, and about one-third were on combination treatment. Controls were similar demographically with a mean age of 57 years, and 52% were men.

Interestingly, Psoriasis Area and Severity Index (PASI) scores did not correlate with increased risk. During discussion after the presentation of the study, a researcher unaffiliated with the study offered an answer. “It could be their skin disease was controlled by the biologics. You had 67% on biologics,” said Nehal Mehta, MD, Clinical Research Scholar in the section of inflammation and cardiometabolic disease at the National Heart, Lung, and Blood Institute. “We at the NIH see a strong correlation between PASI and coronary artery disease risk.”

“We know methotrexate and anti-TNF agents can have a protective effect on atherosclerosis, but we did not look at this specifically,” Dr. Szentpetery said. Overall, PASI scores were relatively low in the study population, she added, which “may explain why we did not see the correlation with PASI scores.”

Dr. Szentpetery and Dr. Mehta had no relevant financial disclosures.

MIAMI – Patients with psoriatic arthritis had a higher prevalence and greater extent of coronary artery plaque in a pilot study comparison with healthy control patients that may point to increased risk independent of traditional cardiovascular risk factors.

In the study, coronary artery plaque as assessed by cardiac computed tomography angiography (CCTA) occurred in 39 (78%) of 50 patients with psoriatic arthritis, a significantly higher rate than that observed for healthy controls (11 of 25, 44%).

©vizualis/thinkstockphotos.com

Investigators not only measured plaque volume, but also assessed the type of plaque: calcified, noncalcified, or mixed. Mixed plaque predominated. This could be important because “noncalcified and mixed carry higher risk for rupture and later cardiovascular events,” Agnes Szentpetery, MD, a research fellow at St. Vincent’s University Hospital in Dublin, said at the annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis.

She and her colleagues also found more clinically significant stenosis among the 50 participants with psoriatic arthritis, compared with 25 healthy controls matched for age, sex, smoking status, and presence of metabolic syndrome. “This pilot study is the first to assess coronary plaques in asymptomatic patients with psoriatic arthritis with CCTA,” Dr. Szentpetery said.

Total plaque volume was higher in the psoriatic arthritis group versus controls, and higher in the left main artery for psoriatic arthritis patients, both with and without metabolic syndrome.

The study points to increased risk independent of traditional cardiovascular risk factors. For example, CCTA revealed no difference in plaque volume between patients with and without metabolic disease. In addition, a previous study suggests “the burden of carotid artery plaques is higher in patients with psoriatic arthritis compared to those with psoriasis alone,” Dr. Szentpetery said, citing a cross-sectional study comparing 125 people with psoriasis to 114 others with psoriatic arthritis (Ann Rheum Dis. 2013 May;72[5]:715-20).

Perhaps not surprisingly, inflammation could be driving the association between psoriatic and cardiovascular disease risk. Other investigators suggest chronic, low-grade inflammation leads to atherosclerosis through a maladaptive immune response and altered lipid metabolism, for example (Nat Med. 2011 Nov;17[11]:1410-22).

In the current study, the patients with psoriatic arthritis had well-established disease, occurring for a mean duration of 19 years. Mean age was 58 years, and 54% were men. Approximately 60% were taking disease-modifying antirheumatic drugs, two-thirds were taking biologics, and about one-third were on combination treatment. Controls were similar demographically with a mean age of 57 years, and 52% were men.

Interestingly, Psoriasis Area and Severity Index (PASI) scores did not correlate with increased risk. During discussion after the presentation of the study, a researcher unaffiliated with the study offered an answer. “It could be their skin disease was controlled by the biologics. You had 67% on biologics,” said Nehal Mehta, MD, Clinical Research Scholar in the section of inflammation and cardiometabolic disease at the National Heart, Lung, and Blood Institute. “We at the NIH see a strong correlation between PASI and coronary artery disease risk.”

“We know methotrexate and anti-TNF agents can have a protective effect on atherosclerosis, but we did not look at this specifically,” Dr. Szentpetery said. Overall, PASI scores were relatively low in the study population, she added, which “may explain why we did not see the correlation with PASI scores.”

Dr. Szentpetery and Dr. Mehta had no relevant financial disclosures.

MIAMI – Patients with psoriatic arthritis had a higher prevalence and greater extent of coronary artery plaque in a pilot study comparison with healthy control patients that may point to increased risk independent of traditional cardiovascular risk factors.

In the study, coronary artery plaque as assessed by cardiac computed tomography angiography (CCTA) occurred in 39 (78%) of 50 patients with psoriatic arthritis, a significantly higher rate than that observed for healthy controls (11 of 25, 44%).

©vizualis/thinkstockphotos.com

Investigators not only measured plaque volume, but also assessed the type of plaque: calcified, noncalcified, or mixed. Mixed plaque predominated. This could be important because “noncalcified and mixed carry higher risk for rupture and later cardiovascular events,” Agnes Szentpetery, MD, a research fellow at St. Vincent’s University Hospital in Dublin, said at the annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis.

She and her colleagues also found more clinically significant stenosis among the 50 participants with psoriatic arthritis, compared with 25 healthy controls matched for age, sex, smoking status, and presence of metabolic syndrome. “This pilot study is the first to assess coronary plaques in asymptomatic patients with psoriatic arthritis with CCTA,” Dr. Szentpetery said.

Total plaque volume was higher in the psoriatic arthritis group versus controls, and higher in the left main artery for psoriatic arthritis patients, both with and without metabolic syndrome.

The study points to increased risk independent of traditional cardiovascular risk factors. For example, CCTA revealed no difference in plaque volume between patients with and without metabolic disease. In addition, a previous study suggests “the burden of carotid artery plaques is higher in patients with psoriatic arthritis compared to those with psoriasis alone,” Dr. Szentpetery said, citing a cross-sectional study comparing 125 people with psoriasis to 114 others with psoriatic arthritis (Ann Rheum Dis. 2013 May;72[5]:715-20).

Perhaps not surprisingly, inflammation could be driving the association between psoriatic and cardiovascular disease risk. Other investigators suggest chronic, low-grade inflammation leads to atherosclerosis through a maladaptive immune response and altered lipid metabolism, for example (Nat Med. 2011 Nov;17[11]:1410-22).

In the current study, the patients with psoriatic arthritis had well-established disease, occurring for a mean duration of 19 years. Mean age was 58 years, and 54% were men. Approximately 60% were taking disease-modifying antirheumatic drugs, two-thirds were taking biologics, and about one-third were on combination treatment. Controls were similar demographically with a mean age of 57 years, and 52% were men.

Interestingly, Psoriasis Area and Severity Index (PASI) scores did not correlate with increased risk. During discussion after the presentation of the study, a researcher unaffiliated with the study offered an answer. “It could be their skin disease was controlled by the biologics. You had 67% on biologics,” said Nehal Mehta, MD, Clinical Research Scholar in the section of inflammation and cardiometabolic disease at the National Heart, Lung, and Blood Institute. “We at the NIH see a strong correlation between PASI and coronary artery disease risk.”

“We know methotrexate and anti-TNF agents can have a protective effect on atherosclerosis, but we did not look at this specifically,” Dr. Szentpetery said. Overall, PASI scores were relatively low in the study population, she added, which “may explain why we did not see the correlation with PASI scores.”

Dr. Szentpetery and Dr. Mehta had no relevant financial disclosures.

A Food and Drug Administration advisory committee has unanimously supported approval of the monoclonal antibody brodalumab for the treatment of moderate to severe plaque psoriasis, with the majority recommending risk management options beyond labeling to address concerns about the six completed suicides among patients treated with brodalumab in clinical trials.

Though no members of the FDA’s Dermatologic and Ophthalmic Drugs Advisory Committee disputed the drug’s efficacy for plaque psoriasis, the possibility of a signal for suicidal ideation and behavior (SIB) among the brodalumab group prompted the committee’s chair, Michael Bigby, M.D., to remark, “The big problem is that you have six completed suicides. … I would say it’s a fairly big number for a randomized controlled trial. Patients and clinicians need to be aware of this as a fact.”

Dr. Bigby, professor of dermatology at Harvard Medical School, Boston, headed the 18-member panel, which included dermatologists, psychiatrists, and cardiologists. Fourteen members voted in favor of approval with risk management measures beyond labeling; four members voted for approval with labeling alone.

Brodalumab targets interleukin-17 receptors, inhibiting IL-17 uptake and thus blocking the pathway responsible for the cutaneous and systemic signs and symptoms of psoriasis. The pivotal phase III brodalumab studies, AMAGINE-1, -2, and -3, enrolled a total of 4,373 patients with moderate to severe plaque psoriasis. AMAGINE-1 enrolled 661 patients in a 1:1:1 ratio to a randomized, double-blind placebo-controlled study that included two doses of brodalumab: 210 mg and 140 mg. The placebo-controlled phase of the study ran for 12 weeks, followed by a withdrawal and retreatment phase, and after 52 weeks, by an open label long-term extension phase.

AMAGINE-2 (1,831 patients) and AMAGINE-3 (1,881 patients) were identically designed studies that pitted both doses of brodalumab against an active comparator, ustekinumab (Stelara), as well as placebo, in a 2:2:1:1 ratio. This double-blind phase of the study also lasted 12 weeks. During weeks 12-52, patients on the brodalumab arms continued, with an exploration of wider-dose intervals for the 140-mg dose. Patients also continued with ustekinumab, with a rescue option to transition to brodalumab 210 mg. The placebo group could continue on brodalumab 210 mg as well. These two studies also had an open label long-term extension phase.

At the 12-week mark in AMAGINE-1, 41.9% of patients achieved the coprimary endpoint of 100% reduction in the Psoriasis Area and Severity Index (PASI 100) score, compared with 0.5% of those on placebo (P less than .001). AMAGINE-2 and -3 saw 44.4% and 36.7% of the brodalumab 210-mg arms achieving PASI 100 at the 12-week mark, respectively. These figures were significantly higher than the 21.7% and 18.5% reaching PASI 100 on ustekinumab (P less than .001), as well as significantly higher than the less than 1% of patients in the placebo arm who reached that endpoint.

At the end of 52 weeks, 51% of those on brodalumab 210 mg had completely clear skin, compared with 28.1% of the patients receiving ustekinumab (P less than .001).

The safety analysis for brodalumab showed that the most common adverse events were nasopharyngitis, upper respiratory tract infection, headache, and arthralgia; of these, the last two were considered adverse drug reactions. At 52 weeks, those on brodalumab had a slightly greater risk of having nonserious fungal infections than did those on ustekinumab. Overall, however, there was no difference between the brodalumab and ustekinumab arms at week 52 for treatment-emergent adverse events or for serious adverse events.

A cluster of SIB events occurred in 2013 and 2014 during the clinical trials, and the sponsor consulted the FDA. Additional monitoring for suicidal ideation and depression via the Columbia Suicide Severity Rating Scale (C-SSRS) and the Patient Health Questionnaire (PHQ) were implemented at a point where 84% of trial patients were already in the uncontrolled open label extension stage of the trial; in addition, a retrospective data review searched for suicidal ideation and attempts before the implementation of these two tools.

A total of six brodalumab patients completed suicide in all clinical trials, including those for psoriatic arthritis and RA. Suicides included two during the 12- to 52-week follow-up and four during the long-term follow-up phase. Another 29 patients attempted suicide, had intentional self-injury, or had suicidal ideation during these phases of the study, for a total of 35 SIB events. (SIB includes completed suicide, suicide attempt, suicide behavior, and suicide ideation.)*

The significance of the number of completed suicides was difficult to ascertain, given the increased baseline prevalence of depression and related illnesses among patients with psoriasis. Compared with the general population, individuals with psoriasis have hazard ratios of 1.39, 1.31, and 1.44 for depression, anxiety, and suicidality, according to a cohort study cited by Robert Levin, M.D. , director of the division of pharmacovigilance I at the FDA’s Center for Drug Evaluation and Research (CDER).

In addition, monitoring for suicidal ideation and attempts was stepped up during the course of the clinical trials. Brodalumab’s sponsor, Valeant Pharmaceuticals, noted that the rates of suicidal ideation and attempts increased after implementation of the C-SSRS, while other neuropsychiatric symptoms remained stable or declined during the course of the studies. “This makes us think this is ascertainment bias,” said Valeant consultant Lauren Marangell, M.D., a psychiatrist and president of Brain Health Consultants.

Dr. Marangell also reported that, after stratification for preexisting psychiatric comorbidities and risk factors, “there is no question that the rate of SIB is higher in both arms with patients with baseline risk factors.” The FDA’s data analysis showed an 18-fold increase in the rate of SIB for brodalumab arm participants with a prior history of suicidality.

During its presentation, Valeant also pointed out that patients with histories of drug and alcohol abuse, depression, and suicidality were not specifically excluded from the clinical trials. This differentiates the brodalumab program from other biologic studies, “making the studies more characteristic of the real world,” said R.K. Pillai, Ph.D., Valeant vice president.

Dr. Levin’s analysis, one of several independent analyses conducted by different FDA divisions, found that the data were inconclusive. “We currently can’t conclude whether or not these are drug-related risks,” he said. Considering the critical severity of suicide as an outcome, “we must consider the application and regulatory actions carefully.”

Jean Kim, M.D., medical officer in CDER’s division of psychiatry products (DPP), noted that the number of suicides seen in the brodalumab trials “is higher than typically seen in DPP’s large psychiatric drug trials, which involve populations with higher psychiatric morbidity than patients with psoriasis.”

Patients with psoriasis are also known to have a baseline elevated risk of cardiovascular disease, and no committee member felt the brodalumab data showed any additional signal for major adverse cardiovascular events (MACEs) beyond what would be suspected in this population. “I don’t right now see a safety signal for MACE,” said panelist Michael Blaha, M.D., a cardiologist and director of clinical research at Johns Hopkins Ciccarone Center for Prevention of Heart Disease, Baltimore. He noted, however, that research is ongoing to elucidate the relationship between cytokine levels and MACE. “This question about whether cytokines raise or reduce rates for [cardiovascular] events is an open one.”

One of the dermatologists on the committee, Lynn Drake, M.D., said that her decision making was influenced by the disease burden psoriasis inflicts on the patients she sees in her daily practice. “These patients are ill. People tend to think it’s just skin disease. It is not just skin disease. … I’d hate to see our patients deprived of a drug that might help alleviate their symptoms,” said Dr. Drake.

Though committee members voiced some disagreement about whether a patient registry should be established, and if it should be voluntary, they were in agreement that patients and prescribers both be aware of the potential risks of brodalumab, without making any risk management strategy so burdensome that appropriate patients would be deterred from considering the medication. Psoriasis, Dr. Drake said, “is a devastating disease. We need this in our armamentarium.”

The proposed dosing for brodalumab is 210 mg injected subcutaneously weekly for 3 weeks, followed by 210 mg every 2 weeks thereafter.

The FDA usually follows the recommendations of its advisory committees. The panelists had no relevant financial disclosures.

[email protected]

On Twitter @karioakes

*A previous version of this article misstated the number of patients who experienced SIB events.

A Food and Drug Administration advisory committee has unanimously supported approval of the monoclonal antibody brodalumab for the treatment of moderate to severe plaque psoriasis, with the majority recommending risk management options beyond labeling to address concerns about the six completed suicides among patients treated with brodalumab in clinical trials.

Though no members of the FDA’s Dermatologic and Ophthalmic Drugs Advisory Committee disputed the drug’s efficacy for plaque psoriasis, the possibility of a signal for suicidal ideation and behavior (SIB) among the brodalumab group prompted the committee’s chair, Michael Bigby, M.D., to remark, “The big problem is that you have six completed suicides. … I would say it’s a fairly big number for a randomized controlled trial. Patients and clinicians need to be aware of this as a fact.”

Dr. Bigby, professor of dermatology at Harvard Medical School, Boston, headed the 18-member panel, which included dermatologists, psychiatrists, and cardiologists. Fourteen members voted in favor of approval with risk management measures beyond labeling; four members voted for approval with labeling alone.

Brodalumab targets interleukin-17 receptors, inhibiting IL-17 uptake and thus blocking the pathway responsible for the cutaneous and systemic signs and symptoms of psoriasis. The pivotal phase III brodalumab studies, AMAGINE-1, -2, and -3, enrolled a total of 4,373 patients with moderate to severe plaque psoriasis. AMAGINE-1 enrolled 661 patients in a 1:1:1 ratio to a randomized, double-blind placebo-controlled study that included two doses of brodalumab: 210 mg and 140 mg. The placebo-controlled phase of the study ran for 12 weeks, followed by a withdrawal and retreatment phase, and after 52 weeks, by an open label long-term extension phase.

AMAGINE-2 (1,831 patients) and AMAGINE-3 (1,881 patients) were identically designed studies that pitted both doses of brodalumab against an active comparator, ustekinumab (Stelara), as well as placebo, in a 2:2:1:1 ratio. This double-blind phase of the study also lasted 12 weeks. During weeks 12-52, patients on the brodalumab arms continued, with an exploration of wider-dose intervals for the 140-mg dose. Patients also continued with ustekinumab, with a rescue option to transition to brodalumab 210 mg. The placebo group could continue on brodalumab 210 mg as well. These two studies also had an open label long-term extension phase.

At the 12-week mark in AMAGINE-1, 41.9% of patients achieved the coprimary endpoint of 100% reduction in the Psoriasis Area and Severity Index (PASI 100) score, compared with 0.5% of those on placebo (P less than .001). AMAGINE-2 and -3 saw 44.4% and 36.7% of the brodalumab 210-mg arms achieving PASI 100 at the 12-week mark, respectively. These figures were significantly higher than the 21.7% and 18.5% reaching PASI 100 on ustekinumab (P less than .001), as well as significantly higher than the less than 1% of patients in the placebo arm who reached that endpoint.

At the end of 52 weeks, 51% of those on brodalumab 210 mg had completely clear skin, compared with 28.1% of the patients receiving ustekinumab (P less than .001).

The safety analysis for brodalumab showed that the most common adverse events were nasopharyngitis, upper respiratory tract infection, headache, and arthralgia; of these, the last two were considered adverse drug reactions. At 52 weeks, those on brodalumab had a slightly greater risk of having nonserious fungal infections than did those on ustekinumab. Overall, however, there was no difference between the brodalumab and ustekinumab arms at week 52 for treatment-emergent adverse events or for serious adverse events.

A cluster of SIB events occurred in 2013 and 2014 during the clinical trials, and the sponsor consulted the FDA. Additional monitoring for suicidal ideation and depression via the Columbia Suicide Severity Rating Scale (C-SSRS) and the Patient Health Questionnaire (PHQ) were implemented at a point where 84% of trial patients were already in the uncontrolled open label extension stage of the trial; in addition, a retrospective data review searched for suicidal ideation and attempts before the implementation of these two tools.

A total of six brodalumab patients completed suicide in all clinical trials, including those for psoriatic arthritis and RA. Suicides included two during the 12- to 52-week follow-up and four during the long-term follow-up phase. Another 29 patients attempted suicide, had intentional self-injury, or had suicidal ideation during these phases of the study, for a total of 35 SIB events. (SIB includes completed suicide, suicide attempt, suicide behavior, and suicide ideation.)*

The significance of the number of completed suicides was difficult to ascertain, given the increased baseline prevalence of depression and related illnesses among patients with psoriasis. Compared with the general population, individuals with psoriasis have hazard ratios of 1.39, 1.31, and 1.44 for depression, anxiety, and suicidality, according to a cohort study cited by Robert Levin, M.D. , director of the division of pharmacovigilance I at the FDA’s Center for Drug Evaluation and Research (CDER).

In addition, monitoring for suicidal ideation and attempts was stepped up during the course of the clinical trials. Brodalumab’s sponsor, Valeant Pharmaceuticals, noted that the rates of suicidal ideation and attempts increased after implementation of the C-SSRS, while other neuropsychiatric symptoms remained stable or declined during the course of the studies. “This makes us think this is ascertainment bias,” said Valeant consultant Lauren Marangell, M.D., a psychiatrist and president of Brain Health Consultants.

Dr. Marangell also reported that, after stratification for preexisting psychiatric comorbidities and risk factors, “there is no question that the rate of SIB is higher in both arms with patients with baseline risk factors.” The FDA’s data analysis showed an 18-fold increase in the rate of SIB for brodalumab arm participants with a prior history of suicidality.

During its presentation, Valeant also pointed out that patients with histories of drug and alcohol abuse, depression, and suicidality were not specifically excluded from the clinical trials. This differentiates the brodalumab program from other biologic studies, “making the studies more characteristic of the real world,” said R.K. Pillai, Ph.D., Valeant vice president.

Dr. Levin’s analysis, one of several independent analyses conducted by different FDA divisions, found that the data were inconclusive. “We currently can’t conclude whether or not these are drug-related risks,” he said. Considering the critical severity of suicide as an outcome, “we must consider the application and regulatory actions carefully.”

Jean Kim, M.D., medical officer in CDER’s division of psychiatry products (DPP), noted that the number of suicides seen in the brodalumab trials “is higher than typically seen in DPP’s large psychiatric drug trials, which involve populations with higher psychiatric morbidity than patients with psoriasis.”

Patients with psoriasis are also known to have a baseline elevated risk of cardiovascular disease, and no committee member felt the brodalumab data showed any additional signal for major adverse cardiovascular events (MACEs) beyond what would be suspected in this population. “I don’t right now see a safety signal for MACE,” said panelist Michael Blaha, M.D., a cardiologist and director of clinical research at Johns Hopkins Ciccarone Center for Prevention of Heart Disease, Baltimore. He noted, however, that research is ongoing to elucidate the relationship between cytokine levels and MACE. “This question about whether cytokines raise or reduce rates for [cardiovascular] events is an open one.”

One of the dermatologists on the committee, Lynn Drake, M.D., said that her decision making was influenced by the disease burden psoriasis inflicts on the patients she sees in her daily practice. “These patients are ill. People tend to think it’s just skin disease. It is not just skin disease. … I’d hate to see our patients deprived of a drug that might help alleviate their symptoms,” said Dr. Drake.

Though committee members voiced some disagreement about whether a patient registry should be established, and if it should be voluntary, they were in agreement that patients and prescribers both be aware of the potential risks of brodalumab, without making any risk management strategy so burdensome that appropriate patients would be deterred from considering the medication. Psoriasis, Dr. Drake said, “is a devastating disease. We need this in our armamentarium.”

The proposed dosing for brodalumab is 210 mg injected subcutaneously weekly for 3 weeks, followed by 210 mg every 2 weeks thereafter.

The FDA usually follows the recommendations of its advisory committees. The panelists had no relevant financial disclosures.

[email protected]

On Twitter @karioakes

*A previous version of this article misstated the number of patients who experienced SIB events.

A Food and Drug Administration advisory committee has unanimously supported approval of the monoclonal antibody brodalumab for the treatment of moderate to severe plaque psoriasis, with the majority recommending risk management options beyond labeling to address concerns about the six completed suicides among patients treated with brodalumab in clinical trials.

Though no members of the FDA’s Dermatologic and Ophthalmic Drugs Advisory Committee disputed the drug’s efficacy for plaque psoriasis, the possibility of a signal for suicidal ideation and behavior (SIB) among the brodalumab group prompted the committee’s chair, Michael Bigby, M.D., to remark, “The big problem is that you have six completed suicides. … I would say it’s a fairly big number for a randomized controlled trial. Patients and clinicians need to be aware of this as a fact.”

Dr. Bigby, professor of dermatology at Harvard Medical School, Boston, headed the 18-member panel, which included dermatologists, psychiatrists, and cardiologists. Fourteen members voted in favor of approval with risk management measures beyond labeling; four members voted for approval with labeling alone.

Brodalumab targets interleukin-17 receptors, inhibiting IL-17 uptake and thus blocking the pathway responsible for the cutaneous and systemic signs and symptoms of psoriasis. The pivotal phase III brodalumab studies, AMAGINE-1, -2, and -3, enrolled a total of 4,373 patients with moderate to severe plaque psoriasis. AMAGINE-1 enrolled 661 patients in a 1:1:1 ratio to a randomized, double-blind placebo-controlled study that included two doses of brodalumab: 210 mg and 140 mg. The placebo-controlled phase of the study ran for 12 weeks, followed by a withdrawal and retreatment phase, and after 52 weeks, by an open label long-term extension phase.

AMAGINE-2 (1,831 patients) and AMAGINE-3 (1,881 patients) were identically designed studies that pitted both doses of brodalumab against an active comparator, ustekinumab (Stelara), as well as placebo, in a 2:2:1:1 ratio. This double-blind phase of the study also lasted 12 weeks. During weeks 12-52, patients on the brodalumab arms continued, with an exploration of wider-dose intervals for the 140-mg dose. Patients also continued with ustekinumab, with a rescue option to transition to brodalumab 210 mg. The placebo group could continue on brodalumab 210 mg as well. These two studies also had an open label long-term extension phase.

At the 12-week mark in AMAGINE-1, 41.9% of patients achieved the coprimary endpoint of 100% reduction in the Psoriasis Area and Severity Index (PASI 100) score, compared with 0.5% of those on placebo (P less than .001). AMAGINE-2 and -3 saw 44.4% and 36.7% of the brodalumab 210-mg arms achieving PASI 100 at the 12-week mark, respectively. These figures were significantly higher than the 21.7% and 18.5% reaching PASI 100 on ustekinumab (P less than .001), as well as significantly higher than the less than 1% of patients in the placebo arm who reached that endpoint.

At the end of 52 weeks, 51% of those on brodalumab 210 mg had completely clear skin, compared with 28.1% of the patients receiving ustekinumab (P less than .001).

The safety analysis for brodalumab showed that the most common adverse events were nasopharyngitis, upper respiratory tract infection, headache, and arthralgia; of these, the last two were considered adverse drug reactions. At 52 weeks, those on brodalumab had a slightly greater risk of having nonserious fungal infections than did those on ustekinumab. Overall, however, there was no difference between the brodalumab and ustekinumab arms at week 52 for treatment-emergent adverse events or for serious adverse events.

A cluster of SIB events occurred in 2013 and 2014 during the clinical trials, and the sponsor consulted the FDA. Additional monitoring for suicidal ideation and depression via the Columbia Suicide Severity Rating Scale (C-SSRS) and the Patient Health Questionnaire (PHQ) were implemented at a point where 84% of trial patients were already in the uncontrolled open label extension stage of the trial; in addition, a retrospective data review searched for suicidal ideation and attempts before the implementation of these two tools.

A total of six brodalumab patients completed suicide in all clinical trials, including those for psoriatic arthritis and RA. Suicides included two during the 12- to 52-week follow-up and four during the long-term follow-up phase. Another 29 patients attempted suicide, had intentional self-injury, or had suicidal ideation during these phases of the study, for a total of 35 SIB events. (SIB includes completed suicide, suicide attempt, suicide behavior, and suicide ideation.)*

The significance of the number of completed suicides was difficult to ascertain, given the increased baseline prevalence of depression and related illnesses among patients with psoriasis. Compared with the general population, individuals with psoriasis have hazard ratios of 1.39, 1.31, and 1.44 for depression, anxiety, and suicidality, according to a cohort study cited by Robert Levin, M.D. , director of the division of pharmacovigilance I at the FDA’s Center for Drug Evaluation and Research (CDER).

In addition, monitoring for suicidal ideation and attempts was stepped up during the course of the clinical trials. Brodalumab’s sponsor, Valeant Pharmaceuticals, noted that the rates of suicidal ideation and attempts increased after implementation of the C-SSRS, while other neuropsychiatric symptoms remained stable or declined during the course of the studies. “This makes us think this is ascertainment bias,” said Valeant consultant Lauren Marangell, M.D., a psychiatrist and president of Brain Health Consultants.

Dr. Marangell also reported that, after stratification for preexisting psychiatric comorbidities and risk factors, “there is no question that the rate of SIB is higher in both arms with patients with baseline risk factors.” The FDA’s data analysis showed an 18-fold increase in the rate of SIB for brodalumab arm participants with a prior history of suicidality.

During its presentation, Valeant also pointed out that patients with histories of drug and alcohol abuse, depression, and suicidality were not specifically excluded from the clinical trials. This differentiates the brodalumab program from other biologic studies, “making the studies more characteristic of the real world,” said R.K. Pillai, Ph.D., Valeant vice president.

Dr. Levin’s analysis, one of several independent analyses conducted by different FDA divisions, found that the data were inconclusive. “We currently can’t conclude whether or not these are drug-related risks,” he said. Considering the critical severity of suicide as an outcome, “we must consider the application and regulatory actions carefully.”

Jean Kim, M.D., medical officer in CDER’s division of psychiatry products (DPP), noted that the number of suicides seen in the brodalumab trials “is higher than typically seen in DPP’s large psychiatric drug trials, which involve populations with higher psychiatric morbidity than patients with psoriasis.”

Patients with psoriasis are also known to have a baseline elevated risk of cardiovascular disease, and no committee member felt the brodalumab data showed any additional signal for major adverse cardiovascular events (MACEs) beyond what would be suspected in this population. “I don’t right now see a safety signal for MACE,” said panelist Michael Blaha, M.D., a cardiologist and director of clinical research at Johns Hopkins Ciccarone Center for Prevention of Heart Disease, Baltimore. He noted, however, that research is ongoing to elucidate the relationship between cytokine levels and MACE. “This question about whether cytokines raise or reduce rates for [cardiovascular] events is an open one.”

One of the dermatologists on the committee, Lynn Drake, M.D., said that her decision making was influenced by the disease burden psoriasis inflicts on the patients she sees in her daily practice. “These patients are ill. People tend to think it’s just skin disease. It is not just skin disease. … I’d hate to see our patients deprived of a drug that might help alleviate their symptoms,” said Dr. Drake.

Though committee members voiced some disagreement about whether a patient registry should be established, and if it should be voluntary, they were in agreement that patients and prescribers both be aware of the potential risks of brodalumab, without making any risk management strategy so burdensome that appropriate patients would be deterred from considering the medication. Psoriasis, Dr. Drake said, “is a devastating disease. We need this in our armamentarium.”

The proposed dosing for brodalumab is 210 mg injected subcutaneously weekly for 3 weeks, followed by 210 mg every 2 weeks thereafter.

The FDA usually follows the recommendations of its advisory committees. The panelists had no relevant financial disclosures.

[email protected]

On Twitter @karioakes

*A previous version of this article misstated the number of patients who experienced SIB events.

The Food and Drug Administration is currently accepting public comments on the agency’s proposed plans to implement a law that will restrict compounding of human drug products.

A statement issued by the FDA provides links to two draft guidances that describe how the agency “would implement provisions of federal law that restrict compounding human drug products that are essentially copies of commercially available or approved drug products.” One draft guidance and the legal restrictions referenced therein are relevant to physicians and pharmacists, as well as state-licensed pharmacies or federal facilities that compound drugs, according to the FDA. The other guidance applies to outsourcing facilities.

Although compounded drug products, such as a medication made without a dye for a patient allergic to that dye, or a medication made into liquid form for a patient who cannot swallow a pill, “may benefit certain patients whose medical needs cannot be met by a commercially available or an FDA-approved drug product,” the FDA statement said. “Taking compounded drug products that are essentially copies of a commercially available or approved drug needlessly exposes patients to drug products that FDA has not evaluated for safety, effectiveness, and quality. In addition, the compounded drugs may not have been produced according to appropriate quality standards. Such compounding would also undermine the new drug approval and over-the-counter drug monograph systems in the United States.”

The statement refers to serious adverse events, including infections and deaths that have resulted from “poor-quality” compounded drugs.

Written or electronic comments can be submitted until Oct. 11, and information on submitting comments is available at regulations.gov.

[email protected]

The Food and Drug Administration is currently accepting public comments on the agency’s proposed plans to implement a law that will restrict compounding of human drug products.

A statement issued by the FDA provides links to two draft guidances that describe how the agency “would implement provisions of federal law that restrict compounding human drug products that are essentially copies of commercially available or approved drug products.” One draft guidance and the legal restrictions referenced therein are relevant to physicians and pharmacists, as well as state-licensed pharmacies or federal facilities that compound drugs, according to the FDA. The other guidance applies to outsourcing facilities.

Although compounded drug products, such as a medication made without a dye for a patient allergic to that dye, or a medication made into liquid form for a patient who cannot swallow a pill, “may benefit certain patients whose medical needs cannot be met by a commercially available or an FDA-approved drug product,” the FDA statement said. “Taking compounded drug products that are essentially copies of a commercially available or approved drug needlessly exposes patients to drug products that FDA has not evaluated for safety, effectiveness, and quality. In addition, the compounded drugs may not have been produced according to appropriate quality standards. Such compounding would also undermine the new drug approval and over-the-counter drug monograph systems in the United States.”

The statement refers to serious adverse events, including infections and deaths that have resulted from “poor-quality” compounded drugs.

Written or electronic comments can be submitted until Oct. 11, and information on submitting comments is available at regulations.gov.

[email protected]

The Food and Drug Administration is currently accepting public comments on the agency’s proposed plans to implement a law that will restrict compounding of human drug products.

A statement issued by the FDA provides links to two draft guidances that describe how the agency “would implement provisions of federal law that restrict compounding human drug products that are essentially copies of commercially available or approved drug products.” One draft guidance and the legal restrictions referenced therein are relevant to physicians and pharmacists, as well as state-licensed pharmacies or federal facilities that compound drugs, according to the FDA. The other guidance applies to outsourcing facilities.

Although compounded drug products, such as a medication made without a dye for a patient allergic to that dye, or a medication made into liquid form for a patient who cannot swallow a pill, “may benefit certain patients whose medical needs cannot be met by a commercially available or an FDA-approved drug product,” the FDA statement said. “Taking compounded drug products that are essentially copies of a commercially available or approved drug needlessly exposes patients to drug products that FDA has not evaluated for safety, effectiveness, and quality. In addition, the compounded drugs may not have been produced according to appropriate quality standards. Such compounding would also undermine the new drug approval and over-the-counter drug monograph systems in the United States.”

The statement refers to serious adverse events, including infections and deaths that have resulted from “poor-quality” compounded drugs.

Written or electronic comments can be submitted until Oct. 11, and information on submitting comments is available at regulations.gov.

[email protected]

The Food and Drug Administration’s Arthritis Advisory Committee, together with an added complement of dermatologists and gastroenterologists, unanimously recommended during meetings on July 12 and 13 that the agency license a biosimilar Humira (adalimumab) that is made by Amgen and a biosimilar Enbrel (etanercept) that is made by Sandoz for many of the same indications held by the reference drugs.

The FDA advisory panel that endorsed biosimilar Humira recommended the agent’s approval in a 26-0 vote for many, but not all of the indications currently assigned to Humira itself: rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, juvenile idiopathic arthritis in patients at least 4 years old, plaque psoriasis, adult Crohn’s disease, and adult ulcerative colitis.

A slightly different group of 20 advisory panel members (without any gastroenterologists) voted 20-0 in favor of the FDA granting biosimilar Enbrel all five of the indications now held by Enbrel: rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, juvenile idiopathic arthritis, and plaque psoriasis.

The biosimilar Humira and the biosimilar Enbrel are, respectively, the third and fourth candidate biosimilars to emerge from the FDA’s development program and receive advisory committee scrutiny and support. The first agent through the process, biosimilar filgrastim (Zarxio) received FDA approval in 2015 and is available in the United States. Although the second biosimilar through the process, the tumor necrosis factor inhibitor Inflectra that is biosimilar Remicade (infliximab), received FDA approval in April of this year, it has not yet become available for sale, although a spokeswoman for the company that will market it, Pfizer, said that the company expects to start U.S. sales of Inflectra before the end of 2016.

While the Arthritis Advisory Committee ended each of its daylong deliberations for each of the two candidate biosimilars with unanimous support, the panelists’ discussions among themselves and with FDA staffers reflected some uncertainty with the biosimilar concept, especially during the first day when they focused on biosimilar Humira. The major sticking point revolved around the regulatory pathway to approval first established by the Biologics Price Competition and Innovation Act of 2009 and subsequently refined by the FDA that allows a candidate biosimilar to establish its biosimilarity primarily though the results of analytical studies that establish that the candidate molecule is highly similar to the reference molecule. This approval scheme uses clinical trials in a confirmatory role to establish biosimilarity rather than as the linchpin of approval.

It also means that the FDA can grant clinical indications to the biosimilar drug based not on the results from clinical trials, but based entirely on what have already been demonstrated as safe and effective clinical applications for the reference drug. For example, the biosimilar Humira underwent testing in two clinical studies showing similar efficacy and safety as Humira in patients with rheumatoid arthritis and in patients with plaque psoriasis, but received endorsements based on extrapolations for an additional five indications. Biosimilar Enbrel was compared with Enbrel in patients with plaque psoriasis only and still received extrapolated indications for the additional four rheumatologic conditions.

“This is a new level of extrapolation, across indications,” noted Sarah E. Streett, MD, a gastroenterologist at Stanford (Calif.) University, one of several panelists who initially voiced uncertainty about the concept.

But FDA staffer Nikolay P. Nikolov, MD, who led the agency’s presentation, assured the panelists that the concept of extrapolation was at the heart of biosimilar development and regulatory assessment.

“We have confidence from the data that the two molecules [the reference drug and biosimilar drug] are so similar that we can rely on the safety and efficacy of the reference product. The premise of our approach to biosimilars is that this is not a new molecule that we know nothing about.”

The other uncertainty about biosimilar Humira and biosimilar Enbrel that raised concerns of many panelists were the prospects for nonmedical switching once these drugs reach the market. Nonmedical switching refers to when an insurance company or pharmacy benefit manager substitutes a biosimilar for a reference drug without approval from or even the knowledge of the prescribing physician or the patient. Many of the people who spoke during the public forum period on both days of hearings voiced their concerns about this prospect.

“Nonmedical switching is a major concern of clinicians and policy makers, and we need greater clarification from the FDA,” said committee chair Daniel H. Solomon, MD, a rheumatologist and professor of medicine at Harvard Medical School in Boston.

“I see a remarkable disconnect between the public’s concerns [about nonmedical switching] and the charge to the committee. These are essential issues that need a forum to be aired out,” said panelist Steven F. Solga, MD, chief of gastroenterology at St. Luke’s Hospital in Bethlehem, Pa.

Dr. Nikolov assured committee members that the FDA recognized this concern and was working on it. “We appreciate the disconnect between the charge and the concerns of the community. I assure you that the issues brought up will be part of our discussions so we can get this [biosimilar pathway] implemented the right way.”

According to the FDA’s regulations, a biosimilar designation does not allow for nonmedical switching, something that could only happen under a related but distinct designation known as interchangeability. During the committee meeting on July 13, a FDA staffer said that the agency is currently developing guidance for an “interchangeable” designation and plans to have it available before then end of 2016.

[email protected]

On Twitter @mitchelzoler

The Food and Drug Administration’s Arthritis Advisory Committee, together with an added complement of dermatologists and gastroenterologists, unanimously recommended during meetings on July 12 and 13 that the agency license a biosimilar Humira (adalimumab) that is made by Amgen and a biosimilar Enbrel (etanercept) that is made by Sandoz for many of the same indications held by the reference drugs.

The FDA advisory panel that endorsed biosimilar Humira recommended the agent’s approval in a 26-0 vote for many, but not all of the indications currently assigned to Humira itself: rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, juvenile idiopathic arthritis in patients at least 4 years old, plaque psoriasis, adult Crohn’s disease, and adult ulcerative colitis.

A slightly different group of 20 advisory panel members (without any gastroenterologists) voted 20-0 in favor of the FDA granting biosimilar Enbrel all five of the indications now held by Enbrel: rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, juvenile idiopathic arthritis, and plaque psoriasis.

The biosimilar Humira and the biosimilar Enbrel are, respectively, the third and fourth candidate biosimilars to emerge from the FDA’s development program and receive advisory committee scrutiny and support. The first agent through the process, biosimilar filgrastim (Zarxio) received FDA approval in 2015 and is available in the United States. Although the second biosimilar through the process, the tumor necrosis factor inhibitor Inflectra that is biosimilar Remicade (infliximab), received FDA approval in April of this year, it has not yet become available for sale, although a spokeswoman for the company that will market it, Pfizer, said that the company expects to start U.S. sales of Inflectra before the end of 2016.

While the Arthritis Advisory Committee ended each of its daylong deliberations for each of the two candidate biosimilars with unanimous support, the panelists’ discussions among themselves and with FDA staffers reflected some uncertainty with the biosimilar concept, especially during the first day when they focused on biosimilar Humira. The major sticking point revolved around the regulatory pathway to approval first established by the Biologics Price Competition and Innovation Act of 2009 and subsequently refined by the FDA that allows a candidate biosimilar to establish its biosimilarity primarily though the results of analytical studies that establish that the candidate molecule is highly similar to the reference molecule. This approval scheme uses clinical trials in a confirmatory role to establish biosimilarity rather than as the linchpin of approval.

It also means that the FDA can grant clinical indications to the biosimilar drug based not on the results from clinical trials, but based entirely on what have already been demonstrated as safe and effective clinical applications for the reference drug. For example, the biosimilar Humira underwent testing in two clinical studies showing similar efficacy and safety as Humira in patients with rheumatoid arthritis and in patients with plaque psoriasis, but received endorsements based on extrapolations for an additional five indications. Biosimilar Enbrel was compared with Enbrel in patients with plaque psoriasis only and still received extrapolated indications for the additional four rheumatologic conditions.

“This is a new level of extrapolation, across indications,” noted Sarah E. Streett, MD, a gastroenterologist at Stanford (Calif.) University, one of several panelists who initially voiced uncertainty about the concept.

But FDA staffer Nikolay P. Nikolov, MD, who led the agency’s presentation, assured the panelists that the concept of extrapolation was at the heart of biosimilar development and regulatory assessment.

“We have confidence from the data that the two molecules [the reference drug and biosimilar drug] are so similar that we can rely on the safety and efficacy of the reference product. The premise of our approach to biosimilars is that this is not a new molecule that we know nothing about.”

The other uncertainty about biosimilar Humira and biosimilar Enbrel that raised concerns of many panelists were the prospects for nonmedical switching once these drugs reach the market. Nonmedical switching refers to when an insurance company or pharmacy benefit manager substitutes a biosimilar for a reference drug without approval from or even the knowledge of the prescribing physician or the patient. Many of the people who spoke during the public forum period on both days of hearings voiced their concerns about this prospect.

“Nonmedical switching is a major concern of clinicians and policy makers, and we need greater clarification from the FDA,” said committee chair Daniel H. Solomon, MD, a rheumatologist and professor of medicine at Harvard Medical School in Boston.

“I see a remarkable disconnect between the public’s concerns [about nonmedical switching] and the charge to the committee. These are essential issues that need a forum to be aired out,” said panelist Steven F. Solga, MD, chief of gastroenterology at St. Luke’s Hospital in Bethlehem, Pa.

Dr. Nikolov assured committee members that the FDA recognized this concern and was working on it. “We appreciate the disconnect between the charge and the concerns of the community. I assure you that the issues brought up will be part of our discussions so we can get this [biosimilar pathway] implemented the right way.”

According to the FDA’s regulations, a biosimilar designation does not allow for nonmedical switching, something that could only happen under a related but distinct designation known as interchangeability. During the committee meeting on July 13, a FDA staffer said that the agency is currently developing guidance for an “interchangeable” designation and plans to have it available before then end of 2016.

[email protected]

On Twitter @mitchelzoler

The Food and Drug Administration’s Arthritis Advisory Committee, together with an added complement of dermatologists and gastroenterologists, unanimously recommended during meetings on July 12 and 13 that the agency license a biosimilar Humira (adalimumab) that is made by Amgen and a biosimilar Enbrel (etanercept) that is made by Sandoz for many of the same indications held by the reference drugs.

The FDA advisory panel that endorsed biosimilar Humira recommended the agent’s approval in a 26-0 vote for many, but not all of the indications currently assigned to Humira itself: rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, juvenile idiopathic arthritis in patients at least 4 years old, plaque psoriasis, adult Crohn’s disease, and adult ulcerative colitis.

A slightly different group of 20 advisory panel members (without any gastroenterologists) voted 20-0 in favor of the FDA granting biosimilar Enbrel all five of the indications now held by Enbrel: rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, juvenile idiopathic arthritis, and plaque psoriasis.

The biosimilar Humira and the biosimilar Enbrel are, respectively, the third and fourth candidate biosimilars to emerge from the FDA’s development program and receive advisory committee scrutiny and support. The first agent through the process, biosimilar filgrastim (Zarxio) received FDA approval in 2015 and is available in the United States. Although the second biosimilar through the process, the tumor necrosis factor inhibitor Inflectra that is biosimilar Remicade (infliximab), received FDA approval in April of this year, it has not yet become available for sale, although a spokeswoman for the company that will market it, Pfizer, said that the company expects to start U.S. sales of Inflectra before the end of 2016.

While the Arthritis Advisory Committee ended each of its daylong deliberations for each of the two candidate biosimilars with unanimous support, the panelists’ discussions among themselves and with FDA staffers reflected some uncertainty with the biosimilar concept, especially during the first day when they focused on biosimilar Humira. The major sticking point revolved around the regulatory pathway to approval first established by the Biologics Price Competition and Innovation Act of 2009 and subsequently refined by the FDA that allows a candidate biosimilar to establish its biosimilarity primarily though the results of analytical studies that establish that the candidate molecule is highly similar to the reference molecule. This approval scheme uses clinical trials in a confirmatory role to establish biosimilarity rather than as the linchpin of approval.

It also means that the FDA can grant clinical indications to the biosimilar drug based not on the results from clinical trials, but based entirely on what have already been demonstrated as safe and effective clinical applications for the reference drug. For example, the biosimilar Humira underwent testing in two clinical studies showing similar efficacy and safety as Humira in patients with rheumatoid arthritis and in patients with plaque psoriasis, but received endorsements based on extrapolations for an additional five indications. Biosimilar Enbrel was compared with Enbrel in patients with plaque psoriasis only and still received extrapolated indications for the additional four rheumatologic conditions.

“This is a new level of extrapolation, across indications,” noted Sarah E. Streett, MD, a gastroenterologist at Stanford (Calif.) University, one of several panelists who initially voiced uncertainty about the concept.

But FDA staffer Nikolay P. Nikolov, MD, who led the agency’s presentation, assured the panelists that the concept of extrapolation was at the heart of biosimilar development and regulatory assessment.

“We have confidence from the data that the two molecules [the reference drug and biosimilar drug] are so similar that we can rely on the safety and efficacy of the reference product. The premise of our approach to biosimilars is that this is not a new molecule that we know nothing about.”

The other uncertainty about biosimilar Humira and biosimilar Enbrel that raised concerns of many panelists were the prospects for nonmedical switching once these drugs reach the market. Nonmedical switching refers to when an insurance company or pharmacy benefit manager substitutes a biosimilar for a reference drug without approval from or even the knowledge of the prescribing physician or the patient. Many of the people who spoke during the public forum period on both days of hearings voiced their concerns about this prospect.

“Nonmedical switching is a major concern of clinicians and policy makers, and we need greater clarification from the FDA,” said committee chair Daniel H. Solomon, MD, a rheumatologist and professor of medicine at Harvard Medical School in Boston.

“I see a remarkable disconnect between the public’s concerns [about nonmedical switching] and the charge to the committee. These are essential issues that need a forum to be aired out,” said panelist Steven F. Solga, MD, chief of gastroenterology at St. Luke’s Hospital in Bethlehem, Pa.

Dr. Nikolov assured committee members that the FDA recognized this concern and was working on it. “We appreciate the disconnect between the charge and the concerns of the community. I assure you that the issues brought up will be part of our discussions so we can get this [biosimilar pathway] implemented the right way.”

According to the FDA’s regulations, a biosimilar designation does not allow for nonmedical switching, something that could only happen under a related but distinct designation known as interchangeability. During the committee meeting on July 13, a FDA staffer said that the agency is currently developing guidance for an “interchangeable” designation and plans to have it available before then end of 2016.

[email protected]

On Twitter @mitchelzoler

Radiographic vertebral fractures occur frequently in patients with ankylosing spondylitis, according to Dr. Fiona Maas and her associates.

At baseline, 59 (20%) of the 292 patients included in a prospective cohort study had radiographic vertebral fractures. During a 2-year follow-up period, 15 patients developed new fractures and 7 patients experienced an increase in severity of current fractures. A significant majority of fractures were defined as mild, and most were located in the mid-thoracic and thoracolumbar regions of the spine.

Fractures were more likely in patients who were older, had a higher body mass index, had smoked for long durations, had larger occiput-to-wall distances, had more spinal radiographic damage, and had lower hip bone mineral density (BMD). Patients who developed new fractures during the study period were older and had lower hip BMD. Incidence and prevalence of fractures was reduced in patients who were receiving nonsteroidal anti-inflammatory drugs (NSAIDs) at baseline.

“The influence of anti-inflammatory drugs (e.g. NSAIDs, TNF-alpha inhibitors), anti-osteoporotic treatment (e.g. calcium/vitamin D supplements, bisphosphonates), and lifestyle changes (e.g. smoking cessation, body weight control, physical exercise) on the development of vertebral fractures in AS should be further investigated in a large study population with long-term follow-up,” the investigators concluded.

Find the full study in Arthritis Care & Research (doi: 10.1002/acr.22980).

[email protected]

Radiographic vertebral fractures occur frequently in patients with ankylosing spondylitis, according to Dr. Fiona Maas and her associates.

At baseline, 59 (20%) of the 292 patients included in a prospective cohort study had radiographic vertebral fractures. During a 2-year follow-up period, 15 patients developed new fractures and 7 patients experienced an increase in severity of current fractures. A significant majority of fractures were defined as mild, and most were located in the mid-thoracic and thoracolumbar regions of the spine.

Fractures were more likely in patients who were older, had a higher body mass index, had smoked for long durations, had larger occiput-to-wall distances, had more spinal radiographic damage, and had lower hip bone mineral density (BMD). Patients who developed new fractures during the study period were older and had lower hip BMD. Incidence and prevalence of fractures was reduced in patients who were receiving nonsteroidal anti-inflammatory drugs (NSAIDs) at baseline.

“The influence of anti-inflammatory drugs (e.g. NSAIDs, TNF-alpha inhibitors), anti-osteoporotic treatment (e.g. calcium/vitamin D supplements, bisphosphonates), and lifestyle changes (e.g. smoking cessation, body weight control, physical exercise) on the development of vertebral fractures in AS should be further investigated in a large study population with long-term follow-up,” the investigators concluded.

Find the full study in Arthritis Care & Research (doi: 10.1002/acr.22980).

[email protected]

Radiographic vertebral fractures occur frequently in patients with ankylosing spondylitis, according to Dr. Fiona Maas and her associates.

At baseline, 59 (20%) of the 292 patients included in a prospective cohort study had radiographic vertebral fractures. During a 2-year follow-up period, 15 patients developed new fractures and 7 patients experienced an increase in severity of current fractures. A significant majority of fractures were defined as mild, and most were located in the mid-thoracic and thoracolumbar regions of the spine.

Fractures were more likely in patients who were older, had a higher body mass index, had smoked for long durations, had larger occiput-to-wall distances, had more spinal radiographic damage, and had lower hip bone mineral density (BMD). Patients who developed new fractures during the study period were older and had lower hip BMD. Incidence and prevalence of fractures was reduced in patients who were receiving nonsteroidal anti-inflammatory drugs (NSAIDs) at baseline.

“The influence of anti-inflammatory drugs (e.g. NSAIDs, TNF-alpha inhibitors), anti-osteoporotic treatment (e.g. calcium/vitamin D supplements, bisphosphonates), and lifestyle changes (e.g. smoking cessation, body weight control, physical exercise) on the development of vertebral fractures in AS should be further investigated in a large study population with long-term follow-up,” the investigators concluded.

Find the full study in Arthritis Care & Research (doi: 10.1002/acr.22980).

[email protected]

In a 26-0 vote, the Food and Drug Administration’s arthritis advisory committee recommended July 12 that the agency license an Amgen product as biosimilar to Humira (adalimumab) for seven distinct indications: rheumatoid arthritis, juvenile idiopathic arthritis (in patients at least 4 years old), psoriatic arthritis, ankylosing spondylitis, plaque psoriasis, adult Crohn’s disease, and adult ulcerative colitis.

Developing Story

In a 26-0 vote, the Food and Drug Administration’s arthritis advisory committee recommended July 12 that the agency license an Amgen product as biosimilar to Humira (adalimumab) for seven distinct indications: rheumatoid arthritis, juvenile idiopathic arthritis (in patients at least 4 years old), psoriatic arthritis, ankylosing spondylitis, plaque psoriasis, adult Crohn’s disease, and adult ulcerative colitis.

Developing Story

In a 26-0 vote, the Food and Drug Administration’s arthritis advisory committee recommended July 12 that the agency license an Amgen product as biosimilar to Humira (adalimumab) for seven distinct indications: rheumatoid arthritis, juvenile idiopathic arthritis (in patients at least 4 years old), psoriatic arthritis, ankylosing spondylitis, plaque psoriasis, adult Crohn’s disease, and adult ulcerative colitis.

Developing Story

SCOTTSDALE, ARIZ. – Psoriasis of all severities was linked to a 3.5-fold increase in risk of cutaneous T-cell lymphoma, and severe psoriasis upped the associated risk of Hodgkin lymphoma by about 2.5 times, in a large, longitudinal, population-based cohort study.

Psoriasis also was tied to a smaller but statistically significant increase in the risk of non-Hodgkin lymphoma, said Zelma Chiesa Fuxench, MD, of the department of dermatology, the University of Pennsylvania, Philadelphia. Overall, lymphoma risk was highest in people with severe psoriasis, independent of traditional risk factors and exposure to immunosuppressive medications, Dr. Fuxench said at the annual meeting of the Society for Investigative Dermatology.

Courtesy of the Centers for Disease Control and Prevention (CDC)

Psoriasis affects more than 125 million people worldwide, and severe cases are a major cause of cancer-related mortality. “Prior studies have suggested an increased risk of lymphoma in psoriasis patients, but it is unclear if this due to chronic inflammation, exposure to immunosuppressive therapies, or a combination of both factors,” Dr. Fuxench said.

To further explore these links, she and her associates analyzed electronic medical records from THIN (The Health Information Network), which includes about 12 million patients across the United Kingdom. Adults with psoriasis were matched to up to five nonpsoriatic controls based on date and clinic location. Patients who needed systemic medications or phototherapy were categorized as having severe psoriasis. The final dataset included more than 12,000 such patients, as well as 184,000 patients with mild psoriasis and more than 965,000 patients without psoriasis.

Psoriasis patients were younger and more likely to be overweight, male, and smoke and drink alcohol than patients without psoriasis, Dr. Fuxench said. Almost 80% of patients with severe disease had received systemic therapies, most often methotrexate (70% of systemic treatments) or cyclosporine (10%), while only 1% had received biologics.

Patients with severe psoriasis were more likely to be diagnosed with Hodgkin disease, non-Hodgkin lymphoma, and cutaneous T-cell lymphoma than were patients with mild psoriasis or controls. Over a median follow-up of 5.3 years, 34 patients with severe psoriasis were diagnosed with any type of lymphoma, for an incidence of 5.2 cases per 10,000 person-years (95% confidence interval, 3.7-7.3). In contrast, incidence rates for patients with mild psoriasis and controls were 3.3 and 3.2 cases per 10,000 person-years, respectively, Dr. Fuxench said.

In the multivariable analysis, patients with psoriasis were about 18% more likely to develop any type of lymphoma than were controls, an association that reached statistical significance (adjusted hazard ratio, 1.18; 95% CI, 1.06-1.31). Mild psoriasis increased lymphoma risk by 14%, and severe psoriasis upped it by about 83%, and both associations were statistically significant.

The increase in risk of non-Hodgkin lymphoma was 13% greater with mild psoriasis and 56% greater with severe disease, compared with controls, and these associations also reached statistical significance. Mild psoriasis was not linked to Hodgkin lymphoma, but patients with severe psoriasis were about 250% more likely to develop it than controls, with a trend toward statistical significance (aHR, 2.54; 95% CI, 0.94-6.87).

Finally, severe psoriasis was linked to a more than ninefold increase in risk of cutaneous T-cell lymphoma (aHR, 9.3; 95% CI, 4.1-21.4), while mild psoriasis was linked to about a threefold increase in risk.

“These results were robust in multiple sensitivity analyses, including analyses that excluded patients with rheumatoid arthritis, psoriatic arthritis, or a history of exposure to methotrexate, cyclosporine, or biologics,” Dr. Fuxench said. Future studies should explore the effect of treatment timing and selection on cancer risk, she added. “For those of us who care for these patients, we are increasingly using systemic agents that selectively target the immune system, and these questions will arise in clinics.”

The study’s design made it possible to pinpoint dates of diagnosis more effectively than investigators could estimate disease duration or confirm whether patients initially diagnosed with psoriasis actually had cutaneous T-cell lymphoma, Dr. Fuxench noted. “Ideally, we could have another cohort study of incident psoriasis with prospective follow-up, but lymphoma is so rare that there is currently not enough power [in the THIN database] to determine associations.”

The study was funded by grants from the National Institutes of Health and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Dr. Fuxench disclosed unrestricted research funding from Pfizer outside the submitted work.

SCOTTSDALE, ARIZ. – Psoriasis of all severities was linked to a 3.5-fold increase in risk of cutaneous T-cell lymphoma, and severe psoriasis upped the associated risk of Hodgkin lymphoma by about 2.5 times, in a large, longitudinal, population-based cohort study.

Psoriasis also was tied to a smaller but statistically significant increase in the risk of non-Hodgkin lymphoma, said Zelma Chiesa Fuxench, MD, of the department of dermatology, the University of Pennsylvania, Philadelphia. Overall, lymphoma risk was highest in people with severe psoriasis, independent of traditional risk factors and exposure to immunosuppressive medications, Dr. Fuxench said at the annual meeting of the Society for Investigative Dermatology.

Courtesy of the Centers for Disease Control and Prevention (CDC)

Psoriasis affects more than 125 million people worldwide, and severe cases are a major cause of cancer-related mortality. “Prior studies have suggested an increased risk of lymphoma in psoriasis patients, but it is unclear if this due to chronic inflammation, exposure to immunosuppressive therapies, or a combination of both factors,” Dr. Fuxench said.

To further explore these links, she and her associates analyzed electronic medical records from THIN (The Health Information Network), which includes about 12 million patients across the United Kingdom. Adults with psoriasis were matched to up to five nonpsoriatic controls based on date and clinic location. Patients who needed systemic medications or phototherapy were categorized as having severe psoriasis. The final dataset included more than 12,000 such patients, as well as 184,000 patients with mild psoriasis and more than 965,000 patients without psoriasis.

Psoriasis patients were younger and more likely to be overweight, male, and smoke and drink alcohol than patients without psoriasis, Dr. Fuxench said. Almost 80% of patients with severe disease had received systemic therapies, most often methotrexate (70% of systemic treatments) or cyclosporine (10%), while only 1% had received biologics.

Patients with severe psoriasis were more likely to be diagnosed with Hodgkin disease, non-Hodgkin lymphoma, and cutaneous T-cell lymphoma than were patients with mild psoriasis or controls. Over a median follow-up of 5.3 years, 34 patients with severe psoriasis were diagnosed with any type of lymphoma, for an incidence of 5.2 cases per 10,000 person-years (95% confidence interval, 3.7-7.3). In contrast, incidence rates for patients with mild psoriasis and controls were 3.3 and 3.2 cases per 10,000 person-years, respectively, Dr. Fuxench said.

In the multivariable analysis, patients with psoriasis were about 18% more likely to develop any type of lymphoma than were controls, an association that reached statistical significance (adjusted hazard ratio, 1.18; 95% CI, 1.06-1.31). Mild psoriasis increased lymphoma risk by 14%, and severe psoriasis upped it by about 83%, and both associations were statistically significant.

The increase in risk of non-Hodgkin lymphoma was 13% greater with mild psoriasis and 56% greater with severe disease, compared with controls, and these associations also reached statistical significance. Mild psoriasis was not linked to Hodgkin lymphoma, but patients with severe psoriasis were about 250% more likely to develop it than controls, with a trend toward statistical significance (aHR, 2.54; 95% CI, 0.94-6.87).

Finally, severe psoriasis was linked to a more than ninefold increase in risk of cutaneous T-cell lymphoma (aHR, 9.3; 95% CI, 4.1-21.4), while mild psoriasis was linked to about a threefold increase in risk.

“These results were robust in multiple sensitivity analyses, including analyses that excluded patients with rheumatoid arthritis, psoriatic arthritis, or a history of exposure to methotrexate, cyclosporine, or biologics,” Dr. Fuxench said. Future studies should explore the effect of treatment timing and selection on cancer risk, she added. “For those of us who care for these patients, we are increasingly using systemic agents that selectively target the immune system, and these questions will arise in clinics.”

The study’s design made it possible to pinpoint dates of diagnosis more effectively than investigators could estimate disease duration or confirm whether patients initially diagnosed with psoriasis actually had cutaneous T-cell lymphoma, Dr. Fuxench noted. “Ideally, we could have another cohort study of incident psoriasis with prospective follow-up, but lymphoma is so rare that there is currently not enough power [in the THIN database] to determine associations.”

The study was funded by grants from the National Institutes of Health and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Dr. Fuxench disclosed unrestricted research funding from Pfizer outside the submitted work.

SCOTTSDALE, ARIZ. – Psoriasis of all severities was linked to a 3.5-fold increase in risk of cutaneous T-cell lymphoma, and severe psoriasis upped the associated risk of Hodgkin lymphoma by about 2.5 times, in a large, longitudinal, population-based cohort study.

Psoriasis also was tied to a smaller but statistically significant increase in the risk of non-Hodgkin lymphoma, said Zelma Chiesa Fuxench, MD, of the department of dermatology, the University of Pennsylvania, Philadelphia. Overall, lymphoma risk was highest in people with severe psoriasis, independent of traditional risk factors and exposure to immunosuppressive medications, Dr. Fuxench said at the annual meeting of the Society for Investigative Dermatology.

Courtesy of the Centers for Disease Control and Prevention (CDC)

Psoriasis affects more than 125 million people worldwide, and severe cases are a major cause of cancer-related mortality. “Prior studies have suggested an increased risk of lymphoma in psoriasis patients, but it is unclear if this due to chronic inflammation, exposure to immunosuppressive therapies, or a combination of both factors,” Dr. Fuxench said.

To further explore these links, she and her associates analyzed electronic medical records from THIN (The Health Information Network), which includes about 12 million patients across the United Kingdom. Adults with psoriasis were matched to up to five nonpsoriatic controls based on date and clinic location. Patients who needed systemic medications or phototherapy were categorized as having severe psoriasis. The final dataset included more than 12,000 such patients, as well as 184,000 patients with mild psoriasis and more than 965,000 patients without psoriasis.

Psoriasis patients were younger and more likely to be overweight, male, and smoke and drink alcohol than patients without psoriasis, Dr. Fuxench said. Almost 80% of patients with severe disease had received systemic therapies, most often methotrexate (70% of systemic treatments) or cyclosporine (10%), while only 1% had received biologics.

Patients with severe psoriasis were more likely to be diagnosed with Hodgkin disease, non-Hodgkin lymphoma, and cutaneous T-cell lymphoma than were patients with mild psoriasis or controls. Over a median follow-up of 5.3 years, 34 patients with severe psoriasis were diagnosed with any type of lymphoma, for an incidence of 5.2 cases per 10,000 person-years (95% confidence interval, 3.7-7.3). In contrast, incidence rates for patients with mild psoriasis and controls were 3.3 and 3.2 cases per 10,000 person-years, respectively, Dr. Fuxench said.

In the multivariable analysis, patients with psoriasis were about 18% more likely to develop any type of lymphoma than were controls, an association that reached statistical significance (adjusted hazard ratio, 1.18; 95% CI, 1.06-1.31). Mild psoriasis increased lymphoma risk by 14%, and severe psoriasis upped it by about 83%, and both associations were statistically significant.

The increase in risk of non-Hodgkin lymphoma was 13% greater with mild psoriasis and 56% greater with severe disease, compared with controls, and these associations also reached statistical significance. Mild psoriasis was not linked to Hodgkin lymphoma, but patients with severe psoriasis were about 250% more likely to develop it than controls, with a trend toward statistical significance (aHR, 2.54; 95% CI, 0.94-6.87).

Finally, severe psoriasis was linked to a more than ninefold increase in risk of cutaneous T-cell lymphoma (aHR, 9.3; 95% CI, 4.1-21.4), while mild psoriasis was linked to about a threefold increase in risk.

“These results were robust in multiple sensitivity analyses, including analyses that excluded patients with rheumatoid arthritis, psoriatic arthritis, or a history of exposure to methotrexate, cyclosporine, or biologics,” Dr. Fuxench said. Future studies should explore the effect of treatment timing and selection on cancer risk, she added. “For those of us who care for these patients, we are increasingly using systemic agents that selectively target the immune system, and these questions will arise in clinics.”

The study’s design made it possible to pinpoint dates of diagnosis more effectively than investigators could estimate disease duration or confirm whether patients initially diagnosed with psoriasis actually had cutaneous T-cell lymphoma, Dr. Fuxench noted. “Ideally, we could have another cohort study of incident psoriasis with prospective follow-up, but lymphoma is so rare that there is currently not enough power [in the THIN database] to determine associations.”

The study was funded by grants from the National Institutes of Health and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Dr. Fuxench disclosed unrestricted research funding from Pfizer outside the submitted work.