Spondyloarthropathies

AMSTERDAM – Does pushing for a PASI 90 response instead of settling for a PASI 75 matter to patients being treated for moderate-to-severe chronic plaque psoriasis?

You bet it does, Dr. Mark G. Lebwohl asserted at the annual congress of the European Academy of Dermatology and Venereology.

He presented a pooled analysis of data from two large pivotal phase III randomized trials of secukinumab for psoriasis. The primary endpoints in the analysis were how often and how soon patients who achieved a PASI 75 or PASI 90 response at 12 weeks reported obtaining a Dermatology Life Quality Index (DLQI) response, defined as a score of 0 or 1.

The answer: More patients who had a PASI 90 response (meaning almost clear at 12 weeks) had a DLQI response, and it occurred a full 4 weeks faster than in PASI 75 responders – at a median of 8 weeks, compared with 12 weeks, reported Dr. Lebwohl, professor and chairman of the department of dermatology at Mt. Sinai Medical Center in New York.

Scores on the DLQI can range from 0, meaning no psoriasis-related impairment of the patient’s quality of life, up to 30. The average baseline score in this study population was 13.5, so a DLQI response dropping the score down to 0 or 1 represents a dramatic improvement in this patient-reported outcome.

Study participants completed the DLQI questionnaire at weeks 4, 8, 12, 24, 36, and again at week 52. The subjects’ mean baseline PASI score was 23.2.

The two double-blind, randomized, placebo-controlled clinical trials that formed the basis for this analysis were the recently published 52-week ERASURE (Efficacy of Response and Safety of Two Fixed Secukinumab Regimens in Psoriasis) and FIXTURE (Full Year Investigative Examination of Secukinumab vs. Etanercept Using Two Dosing Regimens to Determine Efficacy in Psoriasis) studies (N. Engl. J. Med. 2014;371:326-38), in which patients were assigned to secukinumab at a dose of either 150 mg or 300 mg, placebo, or in the case of FIXTURE, to etanercept. The PASI 75 and 90 response rates at 12 weeks were markedly higher at both doses of secukinumab than with etanercept.

Dr. Lebwohl’s pooled analysis was restricted to the 1,470 study participants in the two studies who were randomized to active therapy. A total of 612 patients achieved a PASI 90 response by week 12. Another 365 had a PASI 75 response. Fully 89% of PASI 90 responders also had a DLQI response maintained out to week 52, as did 77% of PASI 75 responders.

The key finding: The median time to a DLQI response in the PASI 90 responders was 8 weeks, compared with 12 weeks in the PASI 75 responders. Thus, patients with a PASI 90 response obtained virtually total relief from what had previously been a debilitating disease a full month sooner than PASI 75 responders. And that, as reported by the patients themselves, constitutes a meaningful advantage, Dr. Lebwohl stated.

Secukinumab is a fully human monoclonal antibody directed against a novel target: interleukin-17A. Novartis has filed for marketing approval of the biologic agent with an indication for psoriasis both with the Food and Drug Administration and European regulators. Secukinumab is also being developed as a treatment for psoriatic arthritis, rheumatoid arthritis, and ankylosing spondylitis.

Novartis funded the analysis. Dr. Lebwohl reported serving as a consultant to Novartis and more than a dozen other pharmaceutical companies.

bjancin@frontlinemedcom.com

AMSTERDAM – Does pushing for a PASI 90 response instead of settling for a PASI 75 matter to patients being treated for moderate-to-severe chronic plaque psoriasis?

You bet it does, Dr. Mark G. Lebwohl asserted at the annual congress of the European Academy of Dermatology and Venereology.

He presented a pooled analysis of data from two large pivotal phase III randomized trials of secukinumab for psoriasis. The primary endpoints in the analysis were how often and how soon patients who achieved a PASI 75 or PASI 90 response at 12 weeks reported obtaining a Dermatology Life Quality Index (DLQI) response, defined as a score of 0 or 1.

The answer: More patients who had a PASI 90 response (meaning almost clear at 12 weeks) had a DLQI response, and it occurred a full 4 weeks faster than in PASI 75 responders – at a median of 8 weeks, compared with 12 weeks, reported Dr. Lebwohl, professor and chairman of the department of dermatology at Mt. Sinai Medical Center in New York.

Scores on the DLQI can range from 0, meaning no psoriasis-related impairment of the patient’s quality of life, up to 30. The average baseline score in this study population was 13.5, so a DLQI response dropping the score down to 0 or 1 represents a dramatic improvement in this patient-reported outcome.

Study participants completed the DLQI questionnaire at weeks 4, 8, 12, 24, 36, and again at week 52. The subjects’ mean baseline PASI score was 23.2.

The two double-blind, randomized, placebo-controlled clinical trials that formed the basis for this analysis were the recently published 52-week ERASURE (Efficacy of Response and Safety of Two Fixed Secukinumab Regimens in Psoriasis) and FIXTURE (Full Year Investigative Examination of Secukinumab vs. Etanercept Using Two Dosing Regimens to Determine Efficacy in Psoriasis) studies (N. Engl. J. Med. 2014;371:326-38), in which patients were assigned to secukinumab at a dose of either 150 mg or 300 mg, placebo, or in the case of FIXTURE, to etanercept. The PASI 75 and 90 response rates at 12 weeks were markedly higher at both doses of secukinumab than with etanercept.

Dr. Lebwohl’s pooled analysis was restricted to the 1,470 study participants in the two studies who were randomized to active therapy. A total of 612 patients achieved a PASI 90 response by week 12. Another 365 had a PASI 75 response. Fully 89% of PASI 90 responders also had a DLQI response maintained out to week 52, as did 77% of PASI 75 responders.

The key finding: The median time to a DLQI response in the PASI 90 responders was 8 weeks, compared with 12 weeks in the PASI 75 responders. Thus, patients with a PASI 90 response obtained virtually total relief from what had previously been a debilitating disease a full month sooner than PASI 75 responders. And that, as reported by the patients themselves, constitutes a meaningful advantage, Dr. Lebwohl stated.

Secukinumab is a fully human monoclonal antibody directed against a novel target: interleukin-17A. Novartis has filed for marketing approval of the biologic agent with an indication for psoriasis both with the Food and Drug Administration and European regulators. Secukinumab is also being developed as a treatment for psoriatic arthritis, rheumatoid arthritis, and ankylosing spondylitis.

Novartis funded the analysis. Dr. Lebwohl reported serving as a consultant to Novartis and more than a dozen other pharmaceutical companies.

bjancin@frontlinemedcom.com

AMSTERDAM – Does pushing for a PASI 90 response instead of settling for a PASI 75 matter to patients being treated for moderate-to-severe chronic plaque psoriasis?

You bet it does, Dr. Mark G. Lebwohl asserted at the annual congress of the European Academy of Dermatology and Venereology.

He presented a pooled analysis of data from two large pivotal phase III randomized trials of secukinumab for psoriasis. The primary endpoints in the analysis were how often and how soon patients who achieved a PASI 75 or PASI 90 response at 12 weeks reported obtaining a Dermatology Life Quality Index (DLQI) response, defined as a score of 0 or 1.

The answer: More patients who had a PASI 90 response (meaning almost clear at 12 weeks) had a DLQI response, and it occurred a full 4 weeks faster than in PASI 75 responders – at a median of 8 weeks, compared with 12 weeks, reported Dr. Lebwohl, professor and chairman of the department of dermatology at Mt. Sinai Medical Center in New York.

Scores on the DLQI can range from 0, meaning no psoriasis-related impairment of the patient’s quality of life, up to 30. The average baseline score in this study population was 13.5, so a DLQI response dropping the score down to 0 or 1 represents a dramatic improvement in this patient-reported outcome.

Study participants completed the DLQI questionnaire at weeks 4, 8, 12, 24, 36, and again at week 52. The subjects’ mean baseline PASI score was 23.2.

The two double-blind, randomized, placebo-controlled clinical trials that formed the basis for this analysis were the recently published 52-week ERASURE (Efficacy of Response and Safety of Two Fixed Secukinumab Regimens in Psoriasis) and FIXTURE (Full Year Investigative Examination of Secukinumab vs. Etanercept Using Two Dosing Regimens to Determine Efficacy in Psoriasis) studies (N. Engl. J. Med. 2014;371:326-38), in which patients were assigned to secukinumab at a dose of either 150 mg or 300 mg, placebo, or in the case of FIXTURE, to etanercept. The PASI 75 and 90 response rates at 12 weeks were markedly higher at both doses of secukinumab than with etanercept.

Dr. Lebwohl’s pooled analysis was restricted to the 1,470 study participants in the two studies who were randomized to active therapy. A total of 612 patients achieved a PASI 90 response by week 12. Another 365 had a PASI 75 response. Fully 89% of PASI 90 responders also had a DLQI response maintained out to week 52, as did 77% of PASI 75 responders.

The key finding: The median time to a DLQI response in the PASI 90 responders was 8 weeks, compared with 12 weeks in the PASI 75 responders. Thus, patients with a PASI 90 response obtained virtually total relief from what had previously been a debilitating disease a full month sooner than PASI 75 responders. And that, as reported by the patients themselves, constitutes a meaningful advantage, Dr. Lebwohl stated.

Secukinumab is a fully human monoclonal antibody directed against a novel target: interleukin-17A. Novartis has filed for marketing approval of the biologic agent with an indication for psoriasis both with the Food and Drug Administration and European regulators. Secukinumab is also being developed as a treatment for psoriatic arthritis, rheumatoid arthritis, and ankylosing spondylitis.

Novartis funded the analysis. Dr. Lebwohl reported serving as a consultant to Novartis and more than a dozen other pharmaceutical companies.

bjancin@frontlinemedcom.com

The biosimilar age for rheumatology has arrived, and experts expect wider use of previously expensive biologic drugs as biosimilar competition drives prices down and makes biologics more affordable.

An infliximab biosimilar became the first such agent to arrive onto the European market in the second half of 2013, and by the start of 2014, it was already having an impact by, for example, dropping the cost of infliximab by a third in Norway. Norway may have received the biggest biosimilar effect so far because it runs an annual auction for the best prices on competing drugs from manufacturers and then mandates Norwegian clinicians to prescribe the lowest-price option when starting a new therapy.

A U.S. version of this scenario may soon follow. In August 2014, Celltrion and Hospira, the two companies jointly producing and marketing biosimilar forms of infliximab under the names Remsima and Inflectra (in parts of eastern Europe and elsewhere), announced they had submitted a marketing application to the Food and Drug Administration. In the announcement, Celltrion officials said they expected Food and Drug Administration approval within a year. If that were to happen, and if Celltrion mounts a successful patent challenge, the Remsima form of infliximab could become one of the first biosimilars on the U.S. market. (In July, Sandoz – a subsidiary of Novartis – announced it submitted an FDA application for Zarzio, a biosimilar version of filgrastim that until now has been only available as Neupogen, a granulocyte colony–stimulating factor. Biosimilar filgrastim seems like the only contender that could edge out Remsima as the first biosimilar on the U.S. market.)

At least two more biosimilars – a third form of infliximab, and a new form of etanercept – may come next, although rheumatologists following the field caution that additional studies are needed on top of what was reported for these two biosimilars last June at the annual European Congress of Rheumatology.

Lower cost broadens use

With one rheumatology biosimilar already on several global formularies and others nearing that status, the next challenge is convincing clinicians that cut-rate biologics are safe and effective and patients can switch from the brand-name form to a biosimilar without adverse effects. Meanwhile, payers and patients are pressing for biosimilars to cut the high cost of biologic treatment. By making biologic drugs more affordable for more patients, introduction of biosimilars will change patient care, experts said.

“A decrease in price will change how biologics are used in U.S. patients. In the United States today, about half of rheumatoid arthritis (RA) patients receive a biologic,” a rate substantially below where it should be, said Dr. Vibeke Strand, a biopharmaceutical consultant and rheumatologist at Stanford (Calif.) University. “Biosimilars will have a very big impact,” she predicted.

“Clinicians are under a lot of pressure from pharmacies, hospitals, and managed-care organization to avoid expensive medications when possible. Starting a biologic will become easier,” when prices start falling. And adherence may also improve. “Part of why patients don’t take their biologics for more than 1-2 years is they can’t afford the copay. That may change” if prices drop, Dr. Strand said in an interview.

Before biosimilars became available, “countries with low GDPs [gross domestic products] had less access to biologics and more restrictions; richer countries had better access,” noted Dr. Tore K. Kvien, a rheumatologist and professor of rheumatology at the University of Oslo.

Greater affordability and access to biologics is the sole factor driving the biosimilar movement. “Cost is the only reason why you have biosimilars,” noted Dr. Bruce N. Cronstein, a rheumatologist and professor of medicine, pathology, and pharmacology at New York University. Aside from cost, there are, by definition, no meaningful differences between a biosimilar and the reference brand-name formulation.

Biosimilars, Dr. Cronstein said, “will be cheaper, but it won’t be like the difference with generic and brand-name statins. You won’t see a 90% price drop. Maybe we’ll see a 30% or 40% price cut, which is considerable. The biologics are all very expensive drugs. But biosimilars will not lead to anything like the savings with small generic molecules.”

While Dr. Cronstein noted that there are no guarantees regarding the timing of price changes, the extent of price cuts, or how competition might affect pricing of the brand-name alternative, the experience in Norway showed a quick, one-third price cut when Remsima became an option, Dr. Kvien said in an interview. For years, Norway has negotiated 1-year contracts for setting drug costs with manufacturers. Norwegian officials invite competitors to submit bids in an annual auction. Celltrion won the auction to make Remsima the infliximab of choice in Norway during 2014 for all six European Medicines Agency (EMA)-approved infliximab indications: rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, psoriasis, Crohn’s disease, and ulcerative colitis.

“My colleagues tell me that the one-third reduction in price [compared with Remicade's price in 2014] was larger than they expected,” Dr. Kvien said. A year of treatment for an RA patient receiving Remsima averages about 6,000 euro now, down from the roughly 9,000 euro current annual cost for Remicade.

Dr. Strand maintained that economic pressures play a role in how easily biosimilars gain regulatory approval. For example, EMA received pressure from Eastern European countries where biologics have been relatively unavailable because of their price, she said. In the United States, pressure on the FDA comes from payers and patients because biologic copays are so high. But despite pressure, Dr. Strand and others believe that EMA and the FDA have set reasonable approval standards for biosimilars that clinicians can rely on.

“I think for all intents and purposes if EMA decides something is a biosimilar then I definitely think it is,” Dr. Strand said. “There may be subtle differences, but nothing big.” In some cases reference, brand-name biologics themselves have undergone substantial changes from what they originally had been, as happened with Enbrel and Rituxan, she noted. “The FDA will not entertain even a small change in an amino acid sequence, and requires two immunogenicity studies.”

Concerns about safety

But biosimilars may be a special case, where even the regulatory stamp of approval may not fully convince some clinicians.

“There is still quite a bit of skepticism,” Dr. Strand said. “I think there will be less skepticism once more data show that biosimilars are safe. The biggest concern seems to be that if the FDA decides something is not just biosimilar but also equivalent then there might be substitutions by a pharmacist without knowledge of the health care provider. I think there is concern because people are still not sure what biosimilar means. It will take more data to convince some people.”

“I think that physicians will be convinced by the data showing these compounds act in a similar way. What physicians worry about is that while these drugs may look good in a trial there might be some subtle difference that increases drug resistance or anaphylaxis,” said Dr. Cronstein. “I think clinicians will accept biosimilars and use them, but worry that a safety signal may not be seen in clinical trials. I think the FDA is trying to figure out how to be sure that switching from one drug to another does not cause an adverse effect. That is the major potential downside people see.”

The safety of switching to a biosimilar was an important enough issue for the Norwegian government to sponsor a 2.5 million euro trial to address the question. The 500-patient study, slated to start in the fall of 2014, will randomize patients on stable Remicade treatment to either remain on Remicade or switch to Remsima. The NOR-SWITCH trial will include patients with any of the six indications for which Remsima received EMA approval.

Until trial results are available, anticipated to be in 2016, Norway does not sanction switching patients on a stable Remicade regimen to Remsima even though Remsima is the infliximab of choice for patients starting infliximab for the first time. Despite this, some Norwegian departments have already made the switch in some patients, said Dr. Kvien, who is lead investigator for NOR-SWITCH. “They say the scientific data available now are sufficient to show switching is safe, but I do not agree.” The willingness of some Norwegian clinicians to switch their patients now from infliximab to the biosimilar shows how eager they and patients in Norway are to save money with Remsima.

While biosimilars face challenges entering and gaining traction in the European and American markets, they also seem driven by an overwhelming inevitability.

“Biosimilars will absolutely be routine in 10-20 years. They will be accepted, but it will take time,” Dr. Cronstein predicted.

“Biosimilars are here, they are not going away, and as patents run out we’ll see more and more of them,” predicted Dr. Paul Emery, professor of rheumatology at Leeds (England) University, while speaking at the annual European Congress of Rheumatology last June in Paris.

“I expect biosimilars will be important. My hope is that their lower cost will improve access to these treatments and this will mean better treatment for more patients around the world,” Dr. Kvien said.

Dr. Strand has been a consultant to Hospira, Celltrion, Amgen, Pfizer, Epirus, Baxter, and Merck Serono. Dr. Kvien has been a consultant to AbbVie, Bristol-Myers Squibb, Hospira, Celltrion, Pfizer/Wyeth, Merck Serono, Merck Sharp & Dohme, Roche, UCB, Orion, and Takeda. Dr. Cronstein has been a consultant to Pfizer and Merck Serono. Dr. Emery has been a consultant to AbbVie, Bristol-Myers Squibb, Merck, Pfizer, Roche, and Takeda.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

The biosimilar age for rheumatology has arrived, and experts expect wider use of previously expensive biologic drugs as biosimilar competition drives prices down and makes biologics more affordable.

An infliximab biosimilar became the first such agent to arrive onto the European market in the second half of 2013, and by the start of 2014, it was already having an impact by, for example, dropping the cost of infliximab by a third in Norway. Norway may have received the biggest biosimilar effect so far because it runs an annual auction for the best prices on competing drugs from manufacturers and then mandates Norwegian clinicians to prescribe the lowest-price option when starting a new therapy.

A U.S. version of this scenario may soon follow. In August 2014, Celltrion and Hospira, the two companies jointly producing and marketing biosimilar forms of infliximab under the names Remsima and Inflectra (in parts of eastern Europe and elsewhere), announced they had submitted a marketing application to the Food and Drug Administration. In the announcement, Celltrion officials said they expected Food and Drug Administration approval within a year. If that were to happen, and if Celltrion mounts a successful patent challenge, the Remsima form of infliximab could become one of the first biosimilars on the U.S. market. (In July, Sandoz – a subsidiary of Novartis – announced it submitted an FDA application for Zarzio, a biosimilar version of filgrastim that until now has been only available as Neupogen, a granulocyte colony–stimulating factor. Biosimilar filgrastim seems like the only contender that could edge out Remsima as the first biosimilar on the U.S. market.)

At least two more biosimilars – a third form of infliximab, and a new form of etanercept – may come next, although rheumatologists following the field caution that additional studies are needed on top of what was reported for these two biosimilars last June at the annual European Congress of Rheumatology.

Lower cost broadens use

With one rheumatology biosimilar already on several global formularies and others nearing that status, the next challenge is convincing clinicians that cut-rate biologics are safe and effective and patients can switch from the brand-name form to a biosimilar without adverse effects. Meanwhile, payers and patients are pressing for biosimilars to cut the high cost of biologic treatment. By making biologic drugs more affordable for more patients, introduction of biosimilars will change patient care, experts said.

“A decrease in price will change how biologics are used in U.S. patients. In the United States today, about half of rheumatoid arthritis (RA) patients receive a biologic,” a rate substantially below where it should be, said Dr. Vibeke Strand, a biopharmaceutical consultant and rheumatologist at Stanford (Calif.) University. “Biosimilars will have a very big impact,” she predicted.

“Clinicians are under a lot of pressure from pharmacies, hospitals, and managed-care organization to avoid expensive medications when possible. Starting a biologic will become easier,” when prices start falling. And adherence may also improve. “Part of why patients don’t take their biologics for more than 1-2 years is they can’t afford the copay. That may change” if prices drop, Dr. Strand said in an interview.

Before biosimilars became available, “countries with low GDPs [gross domestic products] had less access to biologics and more restrictions; richer countries had better access,” noted Dr. Tore K. Kvien, a rheumatologist and professor of rheumatology at the University of Oslo.

Greater affordability and access to biologics is the sole factor driving the biosimilar movement. “Cost is the only reason why you have biosimilars,” noted Dr. Bruce N. Cronstein, a rheumatologist and professor of medicine, pathology, and pharmacology at New York University. Aside from cost, there are, by definition, no meaningful differences between a biosimilar and the reference brand-name formulation.

Biosimilars, Dr. Cronstein said, “will be cheaper, but it won’t be like the difference with generic and brand-name statins. You won’t see a 90% price drop. Maybe we’ll see a 30% or 40% price cut, which is considerable. The biologics are all very expensive drugs. But biosimilars will not lead to anything like the savings with small generic molecules.”

While Dr. Cronstein noted that there are no guarantees regarding the timing of price changes, the extent of price cuts, or how competition might affect pricing of the brand-name alternative, the experience in Norway showed a quick, one-third price cut when Remsima became an option, Dr. Kvien said in an interview. For years, Norway has negotiated 1-year contracts for setting drug costs with manufacturers. Norwegian officials invite competitors to submit bids in an annual auction. Celltrion won the auction to make Remsima the infliximab of choice in Norway during 2014 for all six European Medicines Agency (EMA)-approved infliximab indications: rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, psoriasis, Crohn’s disease, and ulcerative colitis.

“My colleagues tell me that the one-third reduction in price [compared with Remicade's price in 2014] was larger than they expected,” Dr. Kvien said. A year of treatment for an RA patient receiving Remsima averages about 6,000 euro now, down from the roughly 9,000 euro current annual cost for Remicade.

Dr. Strand maintained that economic pressures play a role in how easily biosimilars gain regulatory approval. For example, EMA received pressure from Eastern European countries where biologics have been relatively unavailable because of their price, she said. In the United States, pressure on the FDA comes from payers and patients because biologic copays are so high. But despite pressure, Dr. Strand and others believe that EMA and the FDA have set reasonable approval standards for biosimilars that clinicians can rely on.

“I think for all intents and purposes if EMA decides something is a biosimilar then I definitely think it is,” Dr. Strand said. “There may be subtle differences, but nothing big.” In some cases reference, brand-name biologics themselves have undergone substantial changes from what they originally had been, as happened with Enbrel and Rituxan, she noted. “The FDA will not entertain even a small change in an amino acid sequence, and requires two immunogenicity studies.”

Concerns about safety

But biosimilars may be a special case, where even the regulatory stamp of approval may not fully convince some clinicians.

“There is still quite a bit of skepticism,” Dr. Strand said. “I think there will be less skepticism once more data show that biosimilars are safe. The biggest concern seems to be that if the FDA decides something is not just biosimilar but also equivalent then there might be substitutions by a pharmacist without knowledge of the health care provider. I think there is concern because people are still not sure what biosimilar means. It will take more data to convince some people.”

“I think that physicians will be convinced by the data showing these compounds act in a similar way. What physicians worry about is that while these drugs may look good in a trial there might be some subtle difference that increases drug resistance or anaphylaxis,” said Dr. Cronstein. “I think clinicians will accept biosimilars and use them, but worry that a safety signal may not be seen in clinical trials. I think the FDA is trying to figure out how to be sure that switching from one drug to another does not cause an adverse effect. That is the major potential downside people see.”

The safety of switching to a biosimilar was an important enough issue for the Norwegian government to sponsor a 2.5 million euro trial to address the question. The 500-patient study, slated to start in the fall of 2014, will randomize patients on stable Remicade treatment to either remain on Remicade or switch to Remsima. The NOR-SWITCH trial will include patients with any of the six indications for which Remsima received EMA approval.

Until trial results are available, anticipated to be in 2016, Norway does not sanction switching patients on a stable Remicade regimen to Remsima even though Remsima is the infliximab of choice for patients starting infliximab for the first time. Despite this, some Norwegian departments have already made the switch in some patients, said Dr. Kvien, who is lead investigator for NOR-SWITCH. “They say the scientific data available now are sufficient to show switching is safe, but I do not agree.” The willingness of some Norwegian clinicians to switch their patients now from infliximab to the biosimilar shows how eager they and patients in Norway are to save money with Remsima.

While biosimilars face challenges entering and gaining traction in the European and American markets, they also seem driven by an overwhelming inevitability.

“Biosimilars will absolutely be routine in 10-20 years. They will be accepted, but it will take time,” Dr. Cronstein predicted.

“Biosimilars are here, they are not going away, and as patents run out we’ll see more and more of them,” predicted Dr. Paul Emery, professor of rheumatology at Leeds (England) University, while speaking at the annual European Congress of Rheumatology last June in Paris.

“I expect biosimilars will be important. My hope is that their lower cost will improve access to these treatments and this will mean better treatment for more patients around the world,” Dr. Kvien said.

Dr. Strand has been a consultant to Hospira, Celltrion, Amgen, Pfizer, Epirus, Baxter, and Merck Serono. Dr. Kvien has been a consultant to AbbVie, Bristol-Myers Squibb, Hospira, Celltrion, Pfizer/Wyeth, Merck Serono, Merck Sharp & Dohme, Roche, UCB, Orion, and Takeda. Dr. Cronstein has been a consultant to Pfizer and Merck Serono. Dr. Emery has been a consultant to AbbVie, Bristol-Myers Squibb, Merck, Pfizer, Roche, and Takeda.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

The biosimilar age for rheumatology has arrived, and experts expect wider use of previously expensive biologic drugs as biosimilar competition drives prices down and makes biologics more affordable.

An infliximab biosimilar became the first such agent to arrive onto the European market in the second half of 2013, and by the start of 2014, it was already having an impact by, for example, dropping the cost of infliximab by a third in Norway. Norway may have received the biggest biosimilar effect so far because it runs an annual auction for the best prices on competing drugs from manufacturers and then mandates Norwegian clinicians to prescribe the lowest-price option when starting a new therapy.

A U.S. version of this scenario may soon follow. In August 2014, Celltrion and Hospira, the two companies jointly producing and marketing biosimilar forms of infliximab under the names Remsima and Inflectra (in parts of eastern Europe and elsewhere), announced they had submitted a marketing application to the Food and Drug Administration. In the announcement, Celltrion officials said they expected Food and Drug Administration approval within a year. If that were to happen, and if Celltrion mounts a successful patent challenge, the Remsima form of infliximab could become one of the first biosimilars on the U.S. market. (In July, Sandoz – a subsidiary of Novartis – announced it submitted an FDA application for Zarzio, a biosimilar version of filgrastim that until now has been only available as Neupogen, a granulocyte colony–stimulating factor. Biosimilar filgrastim seems like the only contender that could edge out Remsima as the first biosimilar on the U.S. market.)

At least two more biosimilars – a third form of infliximab, and a new form of etanercept – may come next, although rheumatologists following the field caution that additional studies are needed on top of what was reported for these two biosimilars last June at the annual European Congress of Rheumatology.

Lower cost broadens use

With one rheumatology biosimilar already on several global formularies and others nearing that status, the next challenge is convincing clinicians that cut-rate biologics are safe and effective and patients can switch from the brand-name form to a biosimilar without adverse effects. Meanwhile, payers and patients are pressing for biosimilars to cut the high cost of biologic treatment. By making biologic drugs more affordable for more patients, introduction of biosimilars will change patient care, experts said.

“A decrease in price will change how biologics are used in U.S. patients. In the United States today, about half of rheumatoid arthritis (RA) patients receive a biologic,” a rate substantially below where it should be, said Dr. Vibeke Strand, a biopharmaceutical consultant and rheumatologist at Stanford (Calif.) University. “Biosimilars will have a very big impact,” she predicted.

“Clinicians are under a lot of pressure from pharmacies, hospitals, and managed-care organization to avoid expensive medications when possible. Starting a biologic will become easier,” when prices start falling. And adherence may also improve. “Part of why patients don’t take their biologics for more than 1-2 years is they can’t afford the copay. That may change” if prices drop, Dr. Strand said in an interview.

Before biosimilars became available, “countries with low GDPs [gross domestic products] had less access to biologics and more restrictions; richer countries had better access,” noted Dr. Tore K. Kvien, a rheumatologist and professor of rheumatology at the University of Oslo.

Greater affordability and access to biologics is the sole factor driving the biosimilar movement. “Cost is the only reason why you have biosimilars,” noted Dr. Bruce N. Cronstein, a rheumatologist and professor of medicine, pathology, and pharmacology at New York University. Aside from cost, there are, by definition, no meaningful differences between a biosimilar and the reference brand-name formulation.

Biosimilars, Dr. Cronstein said, “will be cheaper, but it won’t be like the difference with generic and brand-name statins. You won’t see a 90% price drop. Maybe we’ll see a 30% or 40% price cut, which is considerable. The biologics are all very expensive drugs. But biosimilars will not lead to anything like the savings with small generic molecules.”

While Dr. Cronstein noted that there are no guarantees regarding the timing of price changes, the extent of price cuts, or how competition might affect pricing of the brand-name alternative, the experience in Norway showed a quick, one-third price cut when Remsima became an option, Dr. Kvien said in an interview. For years, Norway has negotiated 1-year contracts for setting drug costs with manufacturers. Norwegian officials invite competitors to submit bids in an annual auction. Celltrion won the auction to make Remsima the infliximab of choice in Norway during 2014 for all six European Medicines Agency (EMA)-approved infliximab indications: rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, psoriasis, Crohn’s disease, and ulcerative colitis.

“My colleagues tell me that the one-third reduction in price [compared with Remicade's price in 2014] was larger than they expected,” Dr. Kvien said. A year of treatment for an RA patient receiving Remsima averages about 6,000 euro now, down from the roughly 9,000 euro current annual cost for Remicade.

Dr. Strand maintained that economic pressures play a role in how easily biosimilars gain regulatory approval. For example, EMA received pressure from Eastern European countries where biologics have been relatively unavailable because of their price, she said. In the United States, pressure on the FDA comes from payers and patients because biologic copays are so high. But despite pressure, Dr. Strand and others believe that EMA and the FDA have set reasonable approval standards for biosimilars that clinicians can rely on.

“I think for all intents and purposes if EMA decides something is a biosimilar then I definitely think it is,” Dr. Strand said. “There may be subtle differences, but nothing big.” In some cases reference, brand-name biologics themselves have undergone substantial changes from what they originally had been, as happened with Enbrel and Rituxan, she noted. “The FDA will not entertain even a small change in an amino acid sequence, and requires two immunogenicity studies.”

Concerns about safety

But biosimilars may be a special case, where even the regulatory stamp of approval may not fully convince some clinicians.

“There is still quite a bit of skepticism,” Dr. Strand said. “I think there will be less skepticism once more data show that biosimilars are safe. The biggest concern seems to be that if the FDA decides something is not just biosimilar but also equivalent then there might be substitutions by a pharmacist without knowledge of the health care provider. I think there is concern because people are still not sure what biosimilar means. It will take more data to convince some people.”

“I think that physicians will be convinced by the data showing these compounds act in a similar way. What physicians worry about is that while these drugs may look good in a trial there might be some subtle difference that increases drug resistance or anaphylaxis,” said Dr. Cronstein. “I think clinicians will accept biosimilars and use them, but worry that a safety signal may not be seen in clinical trials. I think the FDA is trying to figure out how to be sure that switching from one drug to another does not cause an adverse effect. That is the major potential downside people see.”

The safety of switching to a biosimilar was an important enough issue for the Norwegian government to sponsor a 2.5 million euro trial to address the question. The 500-patient study, slated to start in the fall of 2014, will randomize patients on stable Remicade treatment to either remain on Remicade or switch to Remsima. The NOR-SWITCH trial will include patients with any of the six indications for which Remsima received EMA approval.

Until trial results are available, anticipated to be in 2016, Norway does not sanction switching patients on a stable Remicade regimen to Remsima even though Remsima is the infliximab of choice for patients starting infliximab for the first time. Despite this, some Norwegian departments have already made the switch in some patients, said Dr. Kvien, who is lead investigator for NOR-SWITCH. “They say the scientific data available now are sufficient to show switching is safe, but I do not agree.” The willingness of some Norwegian clinicians to switch their patients now from infliximab to the biosimilar shows how eager they and patients in Norway are to save money with Remsima.

While biosimilars face challenges entering and gaining traction in the European and American markets, they also seem driven by an overwhelming inevitability.

“Biosimilars will absolutely be routine in 10-20 years. They will be accepted, but it will take time,” Dr. Cronstein predicted.

“Biosimilars are here, they are not going away, and as patents run out we’ll see more and more of them,” predicted Dr. Paul Emery, professor of rheumatology at Leeds (England) University, while speaking at the annual European Congress of Rheumatology last June in Paris.

“I expect biosimilars will be important. My hope is that their lower cost will improve access to these treatments and this will mean better treatment for more patients around the world,” Dr. Kvien said.

Dr. Strand has been a consultant to Hospira, Celltrion, Amgen, Pfizer, Epirus, Baxter, and Merck Serono. Dr. Kvien has been a consultant to AbbVie, Bristol-Myers Squibb, Hospira, Celltrion, Pfizer/Wyeth, Merck Serono, Merck Sharp & Dohme, Roche, UCB, Orion, and Takeda. Dr. Cronstein has been a consultant to Pfizer and Merck Serono. Dr. Emery has been a consultant to AbbVie, Bristol-Myers Squibb, Merck, Pfizer, Roche, and Takeda.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

The more severe the psoriasis, the greater likelihood of uncontrolled hypertension, according to data from a population-based study. The findings were published online Oct. 15 in JAMA Dermatology.

In patients with diagnosed hypertension, those with moderate to severe psoriasis showed a positive dose-response relationship between their psoriasis activity and high blood pressure, wrote Dr. Junko Takeshita of the University of Pennsylvania, Philadelphia, and her associates (JAMA Dermatol. 2014 Oct. 15 [doi:10.1001/jamadermatol.2014.2094]).

The researchers compared a random sample of 1,322 adults aged 25-64 years with psoriasis and hypertension and 11,977 age- and practice-matched controls with hypertension. The data were taken from a population-based, cross-sectional study nested in a prospective cohort drawn from an electronic medical records database in the United Kingdom.

After investigators adjusted for age, sex, body mass index, smoking and alcohol use status, presence of comorbid conditions, and current use of antihypertensive medications and nonsteroidal anti-inflammatory drugs, they found psoriasis activity and uncontrolled hypertension correlated, with adjusted odds ratios of 0.97 for mild psoriasis,1.20 for moderate psoriasis, and 1.48 for severe psoriasis (P = .01). The likelihood of uncontrolled hypertension among psoriasis overall was also increased, but this increase was not statistically significant.

The study was limited by its cross-sectional design, which make the directionality of the two conditions hard to determine, the researchers noted.

However, the findings suggest that, among patients with hypertension, psoriasis “is independently associated with poorly controlled blood pressure,” and that more effective blood pressure management is warranted in psoriasis patients, especially those with more severe disease.

Dr. Takeshita reported receipt of payment for continuing medical education work related to psoriasis. Coauthor Dr. Joel Gelfand reported serving as a consultant for AbbVie, Amgen, Celgene, Eli Lilly, Janssen Biologics, and others. This study was supported in part by the National Heart, Lung, and Blood Institute and the National Institute of Arthritis and Musculoskeletal and Skin Diseases.

wmcknight@frontlinemedcom.com

On Twitter @whitneymcknight

The more severe the psoriasis, the greater likelihood of uncontrolled hypertension, according to data from a population-based study. The findings were published online Oct. 15 in JAMA Dermatology.

In patients with diagnosed hypertension, those with moderate to severe psoriasis showed a positive dose-response relationship between their psoriasis activity and high blood pressure, wrote Dr. Junko Takeshita of the University of Pennsylvania, Philadelphia, and her associates (JAMA Dermatol. 2014 Oct. 15 [doi:10.1001/jamadermatol.2014.2094]).

The researchers compared a random sample of 1,322 adults aged 25-64 years with psoriasis and hypertension and 11,977 age- and practice-matched controls with hypertension. The data were taken from a population-based, cross-sectional study nested in a prospective cohort drawn from an electronic medical records database in the United Kingdom.

After investigators adjusted for age, sex, body mass index, smoking and alcohol use status, presence of comorbid conditions, and current use of antihypertensive medications and nonsteroidal anti-inflammatory drugs, they found psoriasis activity and uncontrolled hypertension correlated, with adjusted odds ratios of 0.97 for mild psoriasis,1.20 for moderate psoriasis, and 1.48 for severe psoriasis (P = .01). The likelihood of uncontrolled hypertension among psoriasis overall was also increased, but this increase was not statistically significant.

The study was limited by its cross-sectional design, which make the directionality of the two conditions hard to determine, the researchers noted.

However, the findings suggest that, among patients with hypertension, psoriasis “is independently associated with poorly controlled blood pressure,” and that more effective blood pressure management is warranted in psoriasis patients, especially those with more severe disease.

Dr. Takeshita reported receipt of payment for continuing medical education work related to psoriasis. Coauthor Dr. Joel Gelfand reported serving as a consultant for AbbVie, Amgen, Celgene, Eli Lilly, Janssen Biologics, and others. This study was supported in part by the National Heart, Lung, and Blood Institute and the National Institute of Arthritis and Musculoskeletal and Skin Diseases.

wmcknight@frontlinemedcom.com

On Twitter @whitneymcknight

The more severe the psoriasis, the greater likelihood of uncontrolled hypertension, according to data from a population-based study. The findings were published online Oct. 15 in JAMA Dermatology.

In patients with diagnosed hypertension, those with moderate to severe psoriasis showed a positive dose-response relationship between their psoriasis activity and high blood pressure, wrote Dr. Junko Takeshita of the University of Pennsylvania, Philadelphia, and her associates (JAMA Dermatol. 2014 Oct. 15 [doi:10.1001/jamadermatol.2014.2094]).

The researchers compared a random sample of 1,322 adults aged 25-64 years with psoriasis and hypertension and 11,977 age- and practice-matched controls with hypertension. The data were taken from a population-based, cross-sectional study nested in a prospective cohort drawn from an electronic medical records database in the United Kingdom.

After investigators adjusted for age, sex, body mass index, smoking and alcohol use status, presence of comorbid conditions, and current use of antihypertensive medications and nonsteroidal anti-inflammatory drugs, they found psoriasis activity and uncontrolled hypertension correlated, with adjusted odds ratios of 0.97 for mild psoriasis,1.20 for moderate psoriasis, and 1.48 for severe psoriasis (P = .01). The likelihood of uncontrolled hypertension among psoriasis overall was also increased, but this increase was not statistically significant.

The study was limited by its cross-sectional design, which make the directionality of the two conditions hard to determine, the researchers noted.

However, the findings suggest that, among patients with hypertension, psoriasis “is independently associated with poorly controlled blood pressure,” and that more effective blood pressure management is warranted in psoriasis patients, especially those with more severe disease.

Dr. Takeshita reported receipt of payment for continuing medical education work related to psoriasis. Coauthor Dr. Joel Gelfand reported serving as a consultant for AbbVie, Amgen, Celgene, Eli Lilly, Janssen Biologics, and others. This study was supported in part by the National Heart, Lung, and Blood Institute and the National Institute of Arthritis and Musculoskeletal and Skin Diseases.

wmcknight@frontlinemedcom.com

On Twitter @whitneymcknight

AMSTERDAM – One in five psoriasis patients lost more than 5% of baseline body weight while on oral apremilast for 52 weeks in the phase III ESTEEM 1 and ESTEEM 2 trials.

Patients taking apremilast not only experienced marked improvement in their psoriasis, but also much-needed weight loss, Dr. Kristian Reich observed in presenting the ESTEEM trials analysis at the annual congress of the European Academy of Dermatology and Venereology.

“You could see the weight loss in these studies as a side effect. But I think many of us would think that, in a psoriasis population with a mean baseline weight greater than 90 kg, that’s a very good thing to have,” said Dr. Reich of Dermatologikum Hamburg (Germany).

The mechanism for this weight loss remains unclear, Dr. Reich said. The important point is that it proved completely unrelated to the diarrhea, nausea, and vomiting that are common, albeit mild and transient, side effects associated with apremilast, a phosphodiesterase 4 inhibitor. That is, patients who lost significant weight did not have an increased incidence of these GI adverse events. Nor was there any correlation between baseline body weight and weight loss on the drug, he added.

Apremilast (Otezla) was approved by the Food and Drug Administration earlier in 2014 for the treatment of psoriatic arthritis, and in late September for psoriasis, and is the only systemic psoriasis drug that requires no tuberculosis screening or laboratory monitoring. The drug also is being developed as a medication for rheumatoid arthritis and ankylosing spondylitis.

The prospective ESTEEM I and II trials totaled 1,250 patients with moderate to severe psoriasis and a mean baseline weight of 92.6 kg. They were initially randomized 2:1 to 16 weeks of double-blind apremilast at 30 mg twice daily or placebo. At 16 weeks, everyone was placed on apremilast 30 mg b.i.d. through week 32, when a randomized treatment withdrawal phase began that lasted through week 52.

The weight loss associated with apremilast was progressive. Patients continued to lose weight while taking the drug until approximately week 65 of therapy, when weight loss has plateaued in long-term extension studies.

At 16 weeks in the ESTEEM trials, patients on apremilast had a mean 1.51-kg weight loss compared to baseline, while the mean body weight in placebo-treated controls remained unchanged. Also at week 16, 13.7% of the apremilast group and 5.5% of controls demonstrated a greater than 5% weight reduction from baseline.

The 564 patients on apremilast for the full 52 weeks had a mean weight loss from baseline of 1.99 kg, and 19.2% of patients had a weight loss in excess of 5%.

“I would call a 2-kg weight loss over a 1-year period a moderate weight loss. But a greater than 5% weight loss is generally classified by experts as clinically meaningful,” Dr. Reich noted.

While weight loss increased with time on apremilast, the drug’s GI side effects peaked during the first 2 weeks of therapy and tailed off after the first month.

Weight loss in apremilast-treated patients did not lead to any overt medical sequelae. Only 0.2% of patients discontinued the drug because of weight loss.

The ESTEEM analysis showed no sign of any increased risks of major adverse cardiovascular events, malignancies, serious infections, depressive symptoms, or suicidality in apremilast-treated patients, according to Dr. Reich.

“This is a drug known for having a very good safety profile,” he said.

The ESTEEM trials were funded by Celgene, which markets apremilast. Dr. Reich reported receiving research grants from and serving as a consultant to the company.

bjancin@frontlinemedcom.com

AMSTERDAM – One in five psoriasis patients lost more than 5% of baseline body weight while on oral apremilast for 52 weeks in the phase III ESTEEM 1 and ESTEEM 2 trials.

Patients taking apremilast not only experienced marked improvement in their psoriasis, but also much-needed weight loss, Dr. Kristian Reich observed in presenting the ESTEEM trials analysis at the annual congress of the European Academy of Dermatology and Venereology.

“You could see the weight loss in these studies as a side effect. But I think many of us would think that, in a psoriasis population with a mean baseline weight greater than 90 kg, that’s a very good thing to have,” said Dr. Reich of Dermatologikum Hamburg (Germany).

The mechanism for this weight loss remains unclear, Dr. Reich said. The important point is that it proved completely unrelated to the diarrhea, nausea, and vomiting that are common, albeit mild and transient, side effects associated with apremilast, a phosphodiesterase 4 inhibitor. That is, patients who lost significant weight did not have an increased incidence of these GI adverse events. Nor was there any correlation between baseline body weight and weight loss on the drug, he added.

Apremilast (Otezla) was approved by the Food and Drug Administration earlier in 2014 for the treatment of psoriatic arthritis, and in late September for psoriasis, and is the only systemic psoriasis drug that requires no tuberculosis screening or laboratory monitoring. The drug also is being developed as a medication for rheumatoid arthritis and ankylosing spondylitis.

The prospective ESTEEM I and II trials totaled 1,250 patients with moderate to severe psoriasis and a mean baseline weight of 92.6 kg. They were initially randomized 2:1 to 16 weeks of double-blind apremilast at 30 mg twice daily or placebo. At 16 weeks, everyone was placed on apremilast 30 mg b.i.d. through week 32, when a randomized treatment withdrawal phase began that lasted through week 52.

The weight loss associated with apremilast was progressive. Patients continued to lose weight while taking the drug until approximately week 65 of therapy, when weight loss has plateaued in long-term extension studies.

At 16 weeks in the ESTEEM trials, patients on apremilast had a mean 1.51-kg weight loss compared to baseline, while the mean body weight in placebo-treated controls remained unchanged. Also at week 16, 13.7% of the apremilast group and 5.5% of controls demonstrated a greater than 5% weight reduction from baseline.

The 564 patients on apremilast for the full 52 weeks had a mean weight loss from baseline of 1.99 kg, and 19.2% of patients had a weight loss in excess of 5%.

“I would call a 2-kg weight loss over a 1-year period a moderate weight loss. But a greater than 5% weight loss is generally classified by experts as clinically meaningful,” Dr. Reich noted.

While weight loss increased with time on apremilast, the drug’s GI side effects peaked during the first 2 weeks of therapy and tailed off after the first month.

Weight loss in apremilast-treated patients did not lead to any overt medical sequelae. Only 0.2% of patients discontinued the drug because of weight loss.

The ESTEEM analysis showed no sign of any increased risks of major adverse cardiovascular events, malignancies, serious infections, depressive symptoms, or suicidality in apremilast-treated patients, according to Dr. Reich.

“This is a drug known for having a very good safety profile,” he said.

The ESTEEM trials were funded by Celgene, which markets apremilast. Dr. Reich reported receiving research grants from and serving as a consultant to the company.

bjancin@frontlinemedcom.com

AMSTERDAM – One in five psoriasis patients lost more than 5% of baseline body weight while on oral apremilast for 52 weeks in the phase III ESTEEM 1 and ESTEEM 2 trials.

Patients taking apremilast not only experienced marked improvement in their psoriasis, but also much-needed weight loss, Dr. Kristian Reich observed in presenting the ESTEEM trials analysis at the annual congress of the European Academy of Dermatology and Venereology.

“You could see the weight loss in these studies as a side effect. But I think many of us would think that, in a psoriasis population with a mean baseline weight greater than 90 kg, that’s a very good thing to have,” said Dr. Reich of Dermatologikum Hamburg (Germany).

The mechanism for this weight loss remains unclear, Dr. Reich said. The important point is that it proved completely unrelated to the diarrhea, nausea, and vomiting that are common, albeit mild and transient, side effects associated with apremilast, a phosphodiesterase 4 inhibitor. That is, patients who lost significant weight did not have an increased incidence of these GI adverse events. Nor was there any correlation between baseline body weight and weight loss on the drug, he added.

Apremilast (Otezla) was approved by the Food and Drug Administration earlier in 2014 for the treatment of psoriatic arthritis, and in late September for psoriasis, and is the only systemic psoriasis drug that requires no tuberculosis screening or laboratory monitoring. The drug also is being developed as a medication for rheumatoid arthritis and ankylosing spondylitis.

The prospective ESTEEM I and II trials totaled 1,250 patients with moderate to severe psoriasis and a mean baseline weight of 92.6 kg. They were initially randomized 2:1 to 16 weeks of double-blind apremilast at 30 mg twice daily or placebo. At 16 weeks, everyone was placed on apremilast 30 mg b.i.d. through week 32, when a randomized treatment withdrawal phase began that lasted through week 52.

The weight loss associated with apremilast was progressive. Patients continued to lose weight while taking the drug until approximately week 65 of therapy, when weight loss has plateaued in long-term extension studies.

At 16 weeks in the ESTEEM trials, patients on apremilast had a mean 1.51-kg weight loss compared to baseline, while the mean body weight in placebo-treated controls remained unchanged. Also at week 16, 13.7% of the apremilast group and 5.5% of controls demonstrated a greater than 5% weight reduction from baseline.

The 564 patients on apremilast for the full 52 weeks had a mean weight loss from baseline of 1.99 kg, and 19.2% of patients had a weight loss in excess of 5%.

“I would call a 2-kg weight loss over a 1-year period a moderate weight loss. But a greater than 5% weight loss is generally classified by experts as clinically meaningful,” Dr. Reich noted.

While weight loss increased with time on apremilast, the drug’s GI side effects peaked during the first 2 weeks of therapy and tailed off after the first month.

Weight loss in apremilast-treated patients did not lead to any overt medical sequelae. Only 0.2% of patients discontinued the drug because of weight loss.

The ESTEEM analysis showed no sign of any increased risks of major adverse cardiovascular events, malignancies, serious infections, depressive symptoms, or suicidality in apremilast-treated patients, according to Dr. Reich.

“This is a drug known for having a very good safety profile,” he said.

The ESTEEM trials were funded by Celgene, which markets apremilast. Dr. Reich reported receiving research grants from and serving as a consultant to the company.

bjancin@frontlinemedcom.com

Psoriatic dactylitis might be caused by inflammation of the small enthesis pulleys of flexor tendons of affected fingers and toes, according a study using high-resolution MRI.

The findings help explain the association between flexor tenosynovitis and dactylitis in patients with psoriatic arthritis (PsA), said Dr. Ai Lyn Tan of the National Institute for Health Research’s musculoskeletal biomedical research unit at Leeds (England) University.

Dactylitis, also known as sausage digits, affects about 40% of patients with PsA. Past studies have suggested that enthesitis might be the cause but also have found a link between dactylitis and flexor tenosynovitis, the researchers said. Using high-resolution MRI (hr-MRI), they obtained T1- and T2-weighted images and contrast-enhanced MRI of the digits of 12 patients, including 22 dactylic joints. The investigators also imaged 13 finger and toe joints from 10 healthy controls (Ann. Rheum. Dis. 2014 Sept. 26 [doi:10.1136/annrheumdis-2014-205839].

The hr-MRI studies showed that 75% of patients with dactylitis had enthesitis of the collateral ligament insertions of fingers or toes and 50% had enthesitis of the extensor tendon insertions. Three patients – two of whom had received intramuscular steroid injections within 6 weeks of the scan – did not have ligament enthesitis. Patients who had received steroid injections also lacked evidence of extensor tendon enthesitis. Furthermore, flexor tenosynovitis was seen in 75% of patients with dactylitis, the investigators reported.

Abnormalities were less frequent and milder among the healthy controls. None had signal changes in the tendon pulleys or fibrous sheaths, and only one had evidence of mild flexor tenosynovitis (P = .004), they said.

Limitations of the study included its small size, the researchers noted. In addition, nine patients were male and only three were female.

The study was funded by the Medical Research Council and Arthritis Research UK. The authors reported no conflicts of interest.

Psoriatic dactylitis might be caused by inflammation of the small enthesis pulleys of flexor tendons of affected fingers and toes, according a study using high-resolution MRI.

The findings help explain the association between flexor tenosynovitis and dactylitis in patients with psoriatic arthritis (PsA), said Dr. Ai Lyn Tan of the National Institute for Health Research’s musculoskeletal biomedical research unit at Leeds (England) University.

Dactylitis, also known as sausage digits, affects about 40% of patients with PsA. Past studies have suggested that enthesitis might be the cause but also have found a link between dactylitis and flexor tenosynovitis, the researchers said. Using high-resolution MRI (hr-MRI), they obtained T1- and T2-weighted images and contrast-enhanced MRI of the digits of 12 patients, including 22 dactylic joints. The investigators also imaged 13 finger and toe joints from 10 healthy controls (Ann. Rheum. Dis. 2014 Sept. 26 [doi:10.1136/annrheumdis-2014-205839].

The hr-MRI studies showed that 75% of patients with dactylitis had enthesitis of the collateral ligament insertions of fingers or toes and 50% had enthesitis of the extensor tendon insertions. Three patients – two of whom had received intramuscular steroid injections within 6 weeks of the scan – did not have ligament enthesitis. Patients who had received steroid injections also lacked evidence of extensor tendon enthesitis. Furthermore, flexor tenosynovitis was seen in 75% of patients with dactylitis, the investigators reported.

Abnormalities were less frequent and milder among the healthy controls. None had signal changes in the tendon pulleys or fibrous sheaths, and only one had evidence of mild flexor tenosynovitis (P = .004), they said.

Limitations of the study included its small size, the researchers noted. In addition, nine patients were male and only three were female.

The study was funded by the Medical Research Council and Arthritis Research UK. The authors reported no conflicts of interest.

Psoriatic dactylitis might be caused by inflammation of the small enthesis pulleys of flexor tendons of affected fingers and toes, according a study using high-resolution MRI.

The findings help explain the association between flexor tenosynovitis and dactylitis in patients with psoriatic arthritis (PsA), said Dr. Ai Lyn Tan of the National Institute for Health Research’s musculoskeletal biomedical research unit at Leeds (England) University.

Dactylitis, also known as sausage digits, affects about 40% of patients with PsA. Past studies have suggested that enthesitis might be the cause but also have found a link between dactylitis and flexor tenosynovitis, the researchers said. Using high-resolution MRI (hr-MRI), they obtained T1- and T2-weighted images and contrast-enhanced MRI of the digits of 12 patients, including 22 dactylic joints. The investigators also imaged 13 finger and toe joints from 10 healthy controls (Ann. Rheum. Dis. 2014 Sept. 26 [doi:10.1136/annrheumdis-2014-205839].

The hr-MRI studies showed that 75% of patients with dactylitis had enthesitis of the collateral ligament insertions of fingers or toes and 50% had enthesitis of the extensor tendon insertions. Three patients – two of whom had received intramuscular steroid injections within 6 weeks of the scan – did not have ligament enthesitis. Patients who had received steroid injections also lacked evidence of extensor tendon enthesitis. Furthermore, flexor tenosynovitis was seen in 75% of patients with dactylitis, the investigators reported.

Abnormalities were less frequent and milder among the healthy controls. None had signal changes in the tendon pulleys or fibrous sheaths, and only one had evidence of mild flexor tenosynovitis (P = .004), they said.

Limitations of the study included its small size, the researchers noted. In addition, nine patients were male and only three were female.

The study was funded by the Medical Research Council and Arthritis Research UK. The authors reported no conflicts of interest.

Combining tumor necrosis factor-alpha inhibitors with conventional disease-modifying antirheumatic drugs more than doubled the risk of shingles in patients with psoriatic arthritis, according to a retrospective cohort study.

Patients who took drugs from only one class or the other, however, were no more likely to develop herpes zoster than were untreated patients, said Dr. Devy Zisman of Carmel Medical Center in Haifa, Israel, and his associates.

Biological therapies for inflammatory arthritis have been linked to an increased risk of herpes zoster in some analyses. To investigate the issue, Dr. Zisman and associates studied 3,128 patients with psoriatic arthritis from a national Israeli health care database. The patients averaged 50 years of age, and 46% were male (Ann. Rheum. Dis. 2014 Sept. 26 [doi:10.1136/ annrheumdis-2013-205148]).

© clsgraphics/iStockphoto.com

A total of 182 herpes zoster cases occurred during 20,096 person-years of observation, the researchers said. After controlling for sex, age, comorbidities, steroid treatment, and past treatment with conventional DMARDs, the hazard ratio for herpes zoster with coadministration of tumor necrosis factor-alpha (TNF-alpha) inhibitors and conventional DMARDs was 2.37 (95% confidence interval, 1.32-4.22; P = .004), compared with 1.28 for TNF-alpha inhibitors alone (95% CI, 0.69-2.4) and 1.11 for conventional DMARDs alone (95% CI, 0.76-1.62). The anti–TNF-alpha agents studied included infliximab, adalimumab, and etanercept, while DMARDs included salazopyrine, methotrexate, leflunomide, cyclosporine A, azathioprine, and hydroxychloroquine.

The incidence of herpes zoster in patients prescribed combination regimens was 17.86 cases per 1,000 person-years (95% CI, 10.91-27.58), far higher than for patients who took neither DMARDs nor anti–TNF-alpha agents (7.36), took only conventional DMARDs (9.21), or took only TNF-alpha inhibitors (8.64), the investigators reported.

Older age and treatment with steroids were linked to a slight rise in the risk of herpes zoster (HRs, 1.01 and 1.08, respectively), confirming prior findings, Dr. Zisman and his associates said.

The authors reported no funding sources or conflicts of interest.

Combining tumor necrosis factor-alpha inhibitors with conventional disease-modifying antirheumatic drugs more than doubled the risk of shingles in patients with psoriatic arthritis, according to a retrospective cohort study.

Patients who took drugs from only one class or the other, however, were no more likely to develop herpes zoster than were untreated patients, said Dr. Devy Zisman of Carmel Medical Center in Haifa, Israel, and his associates.

Biological therapies for inflammatory arthritis have been linked to an increased risk of herpes zoster in some analyses. To investigate the issue, Dr. Zisman and associates studied 3,128 patients with psoriatic arthritis from a national Israeli health care database. The patients averaged 50 years of age, and 46% were male (Ann. Rheum. Dis. 2014 Sept. 26 [doi:10.1136/ annrheumdis-2013-205148]).

© clsgraphics/iStockphoto.com

A total of 182 herpes zoster cases occurred during 20,096 person-years of observation, the researchers said. After controlling for sex, age, comorbidities, steroid treatment, and past treatment with conventional DMARDs, the hazard ratio for herpes zoster with coadministration of tumor necrosis factor-alpha (TNF-alpha) inhibitors and conventional DMARDs was 2.37 (95% confidence interval, 1.32-4.22; P = .004), compared with 1.28 for TNF-alpha inhibitors alone (95% CI, 0.69-2.4) and 1.11 for conventional DMARDs alone (95% CI, 0.76-1.62). The anti–TNF-alpha agents studied included infliximab, adalimumab, and etanercept, while DMARDs included salazopyrine, methotrexate, leflunomide, cyclosporine A, azathioprine, and hydroxychloroquine.

The incidence of herpes zoster in patients prescribed combination regimens was 17.86 cases per 1,000 person-years (95% CI, 10.91-27.58), far higher than for patients who took neither DMARDs nor anti–TNF-alpha agents (7.36), took only conventional DMARDs (9.21), or took only TNF-alpha inhibitors (8.64), the investigators reported.

Older age and treatment with steroids were linked to a slight rise in the risk of herpes zoster (HRs, 1.01 and 1.08, respectively), confirming prior findings, Dr. Zisman and his associates said.

The authors reported no funding sources or conflicts of interest.

Combining tumor necrosis factor-alpha inhibitors with conventional disease-modifying antirheumatic drugs more than doubled the risk of shingles in patients with psoriatic arthritis, according to a retrospective cohort study.

Patients who took drugs from only one class or the other, however, were no more likely to develop herpes zoster than were untreated patients, said Dr. Devy Zisman of Carmel Medical Center in Haifa, Israel, and his associates.

Biological therapies for inflammatory arthritis have been linked to an increased risk of herpes zoster in some analyses. To investigate the issue, Dr. Zisman and associates studied 3,128 patients with psoriatic arthritis from a national Israeli health care database. The patients averaged 50 years of age, and 46% were male (Ann. Rheum. Dis. 2014 Sept. 26 [doi:10.1136/ annrheumdis-2013-205148]).

© clsgraphics/iStockphoto.com

A total of 182 herpes zoster cases occurred during 20,096 person-years of observation, the researchers said. After controlling for sex, age, comorbidities, steroid treatment, and past treatment with conventional DMARDs, the hazard ratio for herpes zoster with coadministration of tumor necrosis factor-alpha (TNF-alpha) inhibitors and conventional DMARDs was 2.37 (95% confidence interval, 1.32-4.22; P = .004), compared with 1.28 for TNF-alpha inhibitors alone (95% CI, 0.69-2.4) and 1.11 for conventional DMARDs alone (95% CI, 0.76-1.62). The anti–TNF-alpha agents studied included infliximab, adalimumab, and etanercept, while DMARDs included salazopyrine, methotrexate, leflunomide, cyclosporine A, azathioprine, and hydroxychloroquine.

The incidence of herpes zoster in patients prescribed combination regimens was 17.86 cases per 1,000 person-years (95% CI, 10.91-27.58), far higher than for patients who took neither DMARDs nor anti–TNF-alpha agents (7.36), took only conventional DMARDs (9.21), or took only TNF-alpha inhibitors (8.64), the investigators reported.

Older age and treatment with steroids were linked to a slight rise in the risk of herpes zoster (HRs, 1.01 and 1.08, respectively), confirming prior findings, Dr. Zisman and his associates said.

The authors reported no funding sources or conflicts of interest.

Musculoskeletal ultrasound was associated with more than double gains in diagnostic certainty in a prospective cohort of consecutive patients referred for the evaluation of inflammatory arthritis.

Consistent with previous studies, “We found that musculoskeletal ultrasound greatly increased the diagnostic certainty for inflammatory arthritis in general and for RA [rheumatoid arthritis] in particular,” wrote Dr. Hamed Rezaei and coauthors at the Karolinska Institute in Stockholm.

When the investigators added musculoskeletal ultrasound (MSUS) to the assessment of 103 previously undiagnosed persons (mean age, 50 years; 74% female) who were referred to a single center for suspected inflammatory arthritis, the percentage of patients with a confirmed diagnosis rose from 33% before MSUS to 71.8% after (P < .001). Diagnostic confirmation specifically for RA went from 31.1% before MSUS to 61.2% after (P < .001). The imaging results were consistent with the final diagnosis in 95% of patients (Arthritis Res. Ther. 2014;16:448 [doi:10.1186/s13075-014-0448-6]).

The initial clinical assessments included joint examination, tests for acute-phase reactants, rheumatoid factor and anticitrullinated peptide antibody, and radiographs of hands and feet when indicated. A rheumatologist determined the probable presence of inflammatory arthritis generally, and rheumatoid arthritis specifically using a 5-point scale that assessed probability of the diagnosis with 1 point for less than a 20% probability, 2 points for greater than or equal to 20% but less than a 40% probability, and so on.

Following the initial assessment, the wrist, metacarpophalangeal, proximal interphalangeal joints 2-5 in both hands, metatarsophalangeal joints 2-5 in both feet, and any symptomatic joints, were imaged. The rheumatologist was then given the images and asked to use the same scale to once again assess the diagnostic probabilities.

Although the authors of the study pointed to the strength of their probabilistic approach to determining if musculoskeletal imaging improved diagnostic certainty on a 5-point scale, they acknowledged that the treating rheumatologist who performed the initial assessment was aware of her/his own scoring before the musculoskeletal imaging was done and may have felt either motivated to improve the result, or simply operated under the assumption that more information that may lead to increase posttest probability would be available later. However, when the cases were randomly rescored by another rheumatologist, results were reported to be almost identical.

“As expected, the likelihood of having any inflammatory arthritis and especially of having RA in patients with early arthritis symptoms increased with the presence of MSUS findings,” Dr. Rezaei and his colleagues wrote. “MSUS also improved diagnostic accuracy compared to clinical assessment alone, when analyzed in a classical (deterministic) manner; as also shown previously in more than 95% of patients there was agreement between MSUS finding and final diagnosis.”

wmcknight@frontlinemedcom.com

On Twitter @whitneymcknight

Musculoskeletal ultrasound was associated with more than double gains in diagnostic certainty in a prospective cohort of consecutive patients referred for the evaluation of inflammatory arthritis.

Consistent with previous studies, “We found that musculoskeletal ultrasound greatly increased the diagnostic certainty for inflammatory arthritis in general and for RA [rheumatoid arthritis] in particular,” wrote Dr. Hamed Rezaei and coauthors at the Karolinska Institute in Stockholm.

When the investigators added musculoskeletal ultrasound (MSUS) to the assessment of 103 previously undiagnosed persons (mean age, 50 years; 74% female) who were referred to a single center for suspected inflammatory arthritis, the percentage of patients with a confirmed diagnosis rose from 33% before MSUS to 71.8% after (P < .001). Diagnostic confirmation specifically for RA went from 31.1% before MSUS to 61.2% after (P < .001). The imaging results were consistent with the final diagnosis in 95% of patients (Arthritis Res. Ther. 2014;16:448 [doi:10.1186/s13075-014-0448-6]).

The initial clinical assessments included joint examination, tests for acute-phase reactants, rheumatoid factor and anticitrullinated peptide antibody, and radiographs of hands and feet when indicated. A rheumatologist determined the probable presence of inflammatory arthritis generally, and rheumatoid arthritis specifically using a 5-point scale that assessed probability of the diagnosis with 1 point for less than a 20% probability, 2 points for greater than or equal to 20% but less than a 40% probability, and so on.

Following the initial assessment, the wrist, metacarpophalangeal, proximal interphalangeal joints 2-5 in both hands, metatarsophalangeal joints 2-5 in both feet, and any symptomatic joints, were imaged. The rheumatologist was then given the images and asked to use the same scale to once again assess the diagnostic probabilities.

Although the authors of the study pointed to the strength of their probabilistic approach to determining if musculoskeletal imaging improved diagnostic certainty on a 5-point scale, they acknowledged that the treating rheumatologist who performed the initial assessment was aware of her/his own scoring before the musculoskeletal imaging was done and may have felt either motivated to improve the result, or simply operated under the assumption that more information that may lead to increase posttest probability would be available later. However, when the cases were randomly rescored by another rheumatologist, results were reported to be almost identical.

“As expected, the likelihood of having any inflammatory arthritis and especially of having RA in patients with early arthritis symptoms increased with the presence of MSUS findings,” Dr. Rezaei and his colleagues wrote. “MSUS also improved diagnostic accuracy compared to clinical assessment alone, when analyzed in a classical (deterministic) manner; as also shown previously in more than 95% of patients there was agreement between MSUS finding and final diagnosis.”

wmcknight@frontlinemedcom.com

On Twitter @whitneymcknight

Musculoskeletal ultrasound was associated with more than double gains in diagnostic certainty in a prospective cohort of consecutive patients referred for the evaluation of inflammatory arthritis.

Consistent with previous studies, “We found that musculoskeletal ultrasound greatly increased the diagnostic certainty for inflammatory arthritis in general and for RA [rheumatoid arthritis] in particular,” wrote Dr. Hamed Rezaei and coauthors at the Karolinska Institute in Stockholm.

When the investigators added musculoskeletal ultrasound (MSUS) to the assessment of 103 previously undiagnosed persons (mean age, 50 years; 74% female) who were referred to a single center for suspected inflammatory arthritis, the percentage of patients with a confirmed diagnosis rose from 33% before MSUS to 71.8% after (P < .001). Diagnostic confirmation specifically for RA went from 31.1% before MSUS to 61.2% after (P < .001). The imaging results were consistent with the final diagnosis in 95% of patients (Arthritis Res. Ther. 2014;16:448 [doi:10.1186/s13075-014-0448-6]).

The initial clinical assessments included joint examination, tests for acute-phase reactants, rheumatoid factor and anticitrullinated peptide antibody, and radiographs of hands and feet when indicated. A rheumatologist determined the probable presence of inflammatory arthritis generally, and rheumatoid arthritis specifically using a 5-point scale that assessed probability of the diagnosis with 1 point for less than a 20% probability, 2 points for greater than or equal to 20% but less than a 40% probability, and so on.

Following the initial assessment, the wrist, metacarpophalangeal, proximal interphalangeal joints 2-5 in both hands, metatarsophalangeal joints 2-5 in both feet, and any symptomatic joints, were imaged. The rheumatologist was then given the images and asked to use the same scale to once again assess the diagnostic probabilities.

Although the authors of the study pointed to the strength of their probabilistic approach to determining if musculoskeletal imaging improved diagnostic certainty on a 5-point scale, they acknowledged that the treating rheumatologist who performed the initial assessment was aware of her/his own scoring before the musculoskeletal imaging was done and may have felt either motivated to improve the result, or simply operated under the assumption that more information that may lead to increase posttest probability would be available later. However, when the cases were randomly rescored by another rheumatologist, results were reported to be almost identical.

“As expected, the likelihood of having any inflammatory arthritis and especially of having RA in patients with early arthritis symptoms increased with the presence of MSUS findings,” Dr. Rezaei and his colleagues wrote. “MSUS also improved diagnostic accuracy compared to clinical assessment alone, when analyzed in a classical (deterministic) manner; as also shown previously in more than 95% of patients there was agreement between MSUS finding and final diagnosis.”

wmcknight@frontlinemedcom.com

On Twitter @whitneymcknight

SONOMA, CALIF. – Concerns about the risk of developing deep fungal infections in patients on biologic therapies for psoriasis are real, but not as significant as some may think, Dr. Miriam S. Bettencourt said at the annual Coastal Dermatology Symposium.

Data suggest that 98% of all patients who developed deep fungal infection while taking a biologic drug also were taking another immunosuppressant, usually prednisone, said Dr. Bettencourt of the University of Nevada, Las Vegas.

Among a subgroup of patients taking a biologic drug for psoriasis or psoriatic arthritis, the risk of developing a deep fungal infection is significantly lower than among all patients on biologics, she said at the symposium, jointly presented by the University of Louisville (Ky.) and Global Academy for Medical Education. This publication and Global Academy for Medical Education are owned by the same parent company.

Dr. Bettencourt reported having no financial disclosures.

sboschert@frontlinemedcom.com

On Twitter @sherryboschert

SONOMA, CALIF. – Concerns about the risk of developing deep fungal infections in patients on biologic therapies for psoriasis are real, but not as significant as some may think, Dr. Miriam S. Bettencourt said at the annual Coastal Dermatology Symposium.

Data suggest that 98% of all patients who developed deep fungal infection while taking a biologic drug also were taking another immunosuppressant, usually prednisone, said Dr. Bettencourt of the University of Nevada, Las Vegas.

Among a subgroup of patients taking a biologic drug for psoriasis or psoriatic arthritis, the risk of developing a deep fungal infection is significantly lower than among all patients on biologics, she said at the symposium, jointly presented by the University of Louisville (Ky.) and Global Academy for Medical Education. This publication and Global Academy for Medical Education are owned by the same parent company.

Dr. Bettencourt reported having no financial disclosures.

sboschert@frontlinemedcom.com

On Twitter @sherryboschert

SONOMA, CALIF. – Concerns about the risk of developing deep fungal infections in patients on biologic therapies for psoriasis are real, but not as significant as some may think, Dr. Miriam S. Bettencourt said at the annual Coastal Dermatology Symposium.

Data suggest that 98% of all patients who developed deep fungal infection while taking a biologic drug also were taking another immunosuppressant, usually prednisone, said Dr. Bettencourt of the University of Nevada, Las Vegas.

Among a subgroup of patients taking a biologic drug for psoriasis or psoriatic arthritis, the risk of developing a deep fungal infection is significantly lower than among all patients on biologics, she said at the symposium, jointly presented by the University of Louisville (Ky.) and Global Academy for Medical Education. This publication and Global Academy for Medical Education are owned by the same parent company.

Dr. Bettencourt reported having no financial disclosures.

sboschert@frontlinemedcom.com

On Twitter @sherryboschert

The oral phosphodiesterase-4 inhibitor apremilast is now indicated for the treatment of moderate to severe plaque psoriasis.

On Sept. 23, the manufacturer, Celgene, announced that the Food and Drug Administration had approved the expanded indication for apremilast, which was initially approved in March 2014 for treating psoriatic arthritis. The new indication is for the treatment of patients with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy.

Approval was primarily based on the results of two multicenter, randomized, double-blind, placebo-controlled studies of adults with moderate to severe plaque psoriasis, according to Celgene. At 16 weeks, 33% and 29% of those randomized to the 30-mg, twice daily dose of apremilast had achieved at least a 75% reduction in the Psoriasis Area and Severity Index (PASI 75), compared with 5%-6% of those on placebo, according to the prescribing information.

The most common adverse events reported in studies, which affected at least 1% of treated patients and were more common than in patients on placebo, included diarrhea in 17% and nausea in 17%; other adverse events included upper respiratory infection, tension headache, and headache. The warnings and precautions section of the label includes the recommendation to be alert for the emergence or worsening of depression, suicidal thoughts, or other mood changes in patients treated with the drug, and to monitor weight regularly for significant weight loss. In studies, treatment with apremilast has been associated with an increase in reports of depression and significant weight loss.

Celgene markets apremilast as Otezla.

Serious adverse events associated with treatment should be reported to the FDA at 800-332-1088 or www.fda.gov/medwatch.

Information about the pregnancy registry of women exposed to the drug during pregnancy can be obtained at 877-311-8972.

The updated prescribing information is available at http://www.celgene.com/content/uploads/2014/09/psoriasis-pi.pdf

emechcatie@frontlinemedcom.com

The oral phosphodiesterase-4 inhibitor apremilast is now indicated for the treatment of moderate to severe plaque psoriasis.

On Sept. 23, the manufacturer, Celgene, announced that the Food and Drug Administration had approved the expanded indication for apremilast, which was initially approved in March 2014 for treating psoriatic arthritis. The new indication is for the treatment of patients with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy.

Approval was primarily based on the results of two multicenter, randomized, double-blind, placebo-controlled studies of adults with moderate to severe plaque psoriasis, according to Celgene. At 16 weeks, 33% and 29% of those randomized to the 30-mg, twice daily dose of apremilast had achieved at least a 75% reduction in the Psoriasis Area and Severity Index (PASI 75), compared with 5%-6% of those on placebo, according to the prescribing information.

The most common adverse events reported in studies, which affected at least 1% of treated patients and were more common than in patients on placebo, included diarrhea in 17% and nausea in 17%; other adverse events included upper respiratory infection, tension headache, and headache. The warnings and precautions section of the label includes the recommendation to be alert for the emergence or worsening of depression, suicidal thoughts, or other mood changes in patients treated with the drug, and to monitor weight regularly for significant weight loss. In studies, treatment with apremilast has been associated with an increase in reports of depression and significant weight loss.

Celgene markets apremilast as Otezla.

Serious adverse events associated with treatment should be reported to the FDA at 800-332-1088 or www.fda.gov/medwatch.

Information about the pregnancy registry of women exposed to the drug during pregnancy can be obtained at 877-311-8972.

The updated prescribing information is available at http://www.celgene.com/content/uploads/2014/09/psoriasis-pi.pdf

emechcatie@frontlinemedcom.com

The oral phosphodiesterase-4 inhibitor apremilast is now indicated for the treatment of moderate to severe plaque psoriasis.

On Sept. 23, the manufacturer, Celgene, announced that the Food and Drug Administration had approved the expanded indication for apremilast, which was initially approved in March 2014 for treating psoriatic arthritis. The new indication is for the treatment of patients with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy.

Approval was primarily based on the results of two multicenter, randomized, double-blind, placebo-controlled studies of adults with moderate to severe plaque psoriasis, according to Celgene. At 16 weeks, 33% and 29% of those randomized to the 30-mg, twice daily dose of apremilast had achieved at least a 75% reduction in the Psoriasis Area and Severity Index (PASI 75), compared with 5%-6% of those on placebo, according to the prescribing information.

The most common adverse events reported in studies, which affected at least 1% of treated patients and were more common than in patients on placebo, included diarrhea in 17% and nausea in 17%; other adverse events included upper respiratory infection, tension headache, and headache. The warnings and precautions section of the label includes the recommendation to be alert for the emergence or worsening of depression, suicidal thoughts, or other mood changes in patients treated with the drug, and to monitor weight regularly for significant weight loss. In studies, treatment with apremilast has been associated with an increase in reports of depression and significant weight loss.

Celgene markets apremilast as Otezla.

Serious adverse events associated with treatment should be reported to the FDA at 800-332-1088 or www.fda.gov/medwatch.

Information about the pregnancy registry of women exposed to the drug during pregnancy can be obtained at 877-311-8972.

The updated prescribing information is available at http://www.celgene.com/content/uploads/2014/09/psoriasis-pi.pdf

emechcatie@frontlinemedcom.com

LAS VEGAS – A number of drugs are showing promise for the treatment of psoriatic arthritis, but broader improvements are needed with respect to treatment strategies, according to Dr. Iain McInnes.

Earlier diagnosis, appropriate therapies, and treating to target are among the topics he covered in a presentation on maximizing patient outcomes at the annual Perspectives in Rheumatic Diseases.

A recent study demonstrated that even a 6-month delay in the diagnosis of psoriatic arthritis is associated with worse long-term outcomes on several measures. In that study of 283 patients (Ann. Rheum. Dis. 2014 Feb. 13 [doi: 10.1136/annrheumdis-2013-204858]), the median lag time from disease onset to first rheumatological assessment was 1 year, with only 30% of patients being seen by a rheumatologist within 6 months.

Multiple stepwise regression analysis showed that late consulters had a greater risk of developing peripheral joint erosions (odds ratio, 4.25) and had worse Health Assessment Questionnaire scores (odds ratio, 2.2).

One finding that could help with earlier diagnosis is detection of early entheseal involvement, said Dr. McInnes, professor of medicine and director of the Institute of Infection, Immunity and Immunology at the University of Glasgow (Scotland).

Subclinical entheseal involvement appears to predict psoriatic arthritis in patients presenting with psoriasis, he said at the conference.

In one study, the mean Glasgow Ultrasound Enthesitis Scoring System (GUESS) score was 7.9 in patients with psoriasis, compared with 2.9 in controls, and in another study, thickness of the quadriceps tendon was a significant predictor of the development of psoriatic arthritis in those with psoriasis.

A key challenge in maximizing outcomes in psoriatic arthritis is that rheumatoid arthritis and psoriatic arthritis are typically treated as homogeneous for the purposes of drug development, but the two diseases have distinct clinical phenotypes and time course, tissue distribution, tissue cell/molecular features, genetic susceptibility, and probably impact of immune senescence.

In fact, while disease-modifying antirheumatic drugs are included in European League Against Rheumatsm (EULAR) treatment guidelines for psoriatic arthritis, the Methotrexate in Psoriatic Arthritis (MIPA) trial, a 6-month, double-blind, randomized, placebo-controlled trial of methotrexate, showed no benefit for key psoriatic arthritis endpoints at 3 and 6 months (Rheumatology 2012;51:1368-77).

Data on methotrexate combination therapy is limited, but existing clinical trials and registry data show no clear evidence of benefit. Methotrexate also has long-term toxicity issues.

In studies of patients who received anti–tumor necrosis factor therapy, 59%-69% of patients achieved 20% improvement (ACR 20 response), 37%-50% achieved 50% improvement (ACR 50 response), and up to 52% of patients achieved minimal disease activity at various time points. Also, radiographic progression was improved with anti-TNF therapy vs. placebo. However, TNF inhibitors lose efficacy over time in some patients, and are associated with an increased risk of infection.

Other disappointments or unmet needs in psoriatic arthritis are dichotomous skin and joint responses to biologics, lack of established predictors of response to biologics, lack of a cure, and difficulties in achieving sustained remission, Dr. McInnes said.

Future therapeutic options, including several drugs in development, include drugs that target cytokines and their receptors, such as ustekinumab, which targets IL-12/23; secukinumab and ixekizumab, which target IL-17; and brodalumab, which targets IL-17 receptor A. Other potential targets include IL-6 and the IL-6 receptor and IL-23 and the IL-23 receptor.

Studies of ustekinumab, for example, demonstrate beneficial effects on enthesitis, dactylitis, and modified van der Heijde-Sharp score.

Drugs that target intracellular signaling pathways are also being studied in psoriatic arthritis, including JAK family agents such as tofacitinib and phosphodiesterase inhibitors like apremilast.

As for strategies to improve outcomes, the Tight Control in Psoriatic Arthritis (TICOPA) study provided a rationale for treating to target. Current recommendations call for a target of remission or low disease activity.

The availability of highly effective biologics makes minimal level of disease activity a realistic treatment target, Dr. McInnes said.

The conference was held by Global Academy for Medical Education. Global Academy for Medical Education and this news organization are owned by Frontline Medical Communications.

Dr. McInnes reported receiving research/grant support from Pfizer, Bristol-Myers Squibb, AstraZeneca, and Novo Nordisk, and serving as a consultant to Novartis, Bristol-Myers Squibb, Pfizer, and Galapagos. He is a member of scientific advisory boards for AstraZeneca, Crescendo Bioscience, and Janssen Biotech.

LAS VEGAS – A number of drugs are showing promise for the treatment of psoriatic arthritis, but broader improvements are needed with respect to treatment strategies, according to Dr. Iain McInnes.

Earlier diagnosis, appropriate therapies, and treating to target are among the topics he covered in a presentation on maximizing patient outcomes at the annual Perspectives in Rheumatic Diseases.

A recent study demonstrated that even a 6-month delay in the diagnosis of psoriatic arthritis is associated with worse long-term outcomes on several measures. In that study of 283 patients (Ann. Rheum. Dis. 2014 Feb. 13 [doi: 10.1136/annrheumdis-2013-204858]), the median lag time from disease onset to first rheumatological assessment was 1 year, with only 30% of patients being seen by a rheumatologist within 6 months.

Multiple stepwise regression analysis showed that late consulters had a greater risk of developing peripheral joint erosions (odds ratio, 4.25) and had worse Health Assessment Questionnaire scores (odds ratio, 2.2).

One finding that could help with earlier diagnosis is detection of early entheseal involvement, said Dr. McInnes, professor of medicine and director of the Institute of Infection, Immunity and Immunology at the University of Glasgow (Scotland).

Subclinical entheseal involvement appears to predict psoriatic arthritis in patients presenting with psoriasis, he said at the conference.

In one study, the mean Glasgow Ultrasound Enthesitis Scoring System (GUESS) score was 7.9 in patients with psoriasis, compared with 2.9 in controls, and in another study, thickness of the quadriceps tendon was a significant predictor of the development of psoriatic arthritis in those with psoriasis.

A key challenge in maximizing outcomes in psoriatic arthritis is that rheumatoid arthritis and psoriatic arthritis are typically treated as homogeneous for the purposes of drug development, but the two diseases have distinct clinical phenotypes and time course, tissue distribution, tissue cell/molecular features, genetic susceptibility, and probably impact of immune senescence.

In fact, while disease-modifying antirheumatic drugs are included in European League Against Rheumatsm (EULAR) treatment guidelines for psoriatic arthritis, the Methotrexate in Psoriatic Arthritis (MIPA) trial, a 6-month, double-blind, randomized, placebo-controlled trial of methotrexate, showed no benefit for key psoriatic arthritis endpoints at 3 and 6 months (Rheumatology 2012;51:1368-77).

Data on methotrexate combination therapy is limited, but existing clinical trials and registry data show no clear evidence of benefit. Methotrexate also has long-term toxicity issues.

In studies of patients who received anti–tumor necrosis factor therapy, 59%-69% of patients achieved 20% improvement (ACR 20 response), 37%-50% achieved 50% improvement (ACR 50 response), and up to 52% of patients achieved minimal disease activity at various time points. Also, radiographic progression was improved with anti-TNF therapy vs. placebo. However, TNF inhibitors lose efficacy over time in some patients, and are associated with an increased risk of infection.

Other disappointments or unmet needs in psoriatic arthritis are dichotomous skin and joint responses to biologics, lack of established predictors of response to biologics, lack of a cure, and difficulties in achieving sustained remission, Dr. McInnes said.

Future therapeutic options, including several drugs in development, include drugs that target cytokines and their receptors, such as ustekinumab, which targets IL-12/23; secukinumab and ixekizumab, which target IL-17; and brodalumab, which targets IL-17 receptor A. Other potential targets include IL-6 and the IL-6 receptor and IL-23 and the IL-23 receptor.

Studies of ustekinumab, for example, demonstrate beneficial effects on enthesitis, dactylitis, and modified van der Heijde-Sharp score.

Drugs that target intracellular signaling pathways are also being studied in psoriatic arthritis, including JAK family agents such as tofacitinib and phosphodiesterase inhibitors like apremilast.

As for strategies to improve outcomes, the Tight Control in Psoriatic Arthritis (TICOPA) study provided a rationale for treating to target. Current recommendations call for a target of remission or low disease activity.

The availability of highly effective biologics makes minimal level of disease activity a realistic treatment target, Dr. McInnes said.

The conference was held by Global Academy for Medical Education. Global Academy for Medical Education and this news organization are owned by Frontline Medical Communications.

Dr. McInnes reported receiving research/grant support from Pfizer, Bristol-Myers Squibb, AstraZeneca, and Novo Nordisk, and serving as a consultant to Novartis, Bristol-Myers Squibb, Pfizer, and Galapagos. He is a member of scientific advisory boards for AstraZeneca, Crescendo Bioscience, and Janssen Biotech.

LAS VEGAS – A number of drugs are showing promise for the treatment of psoriatic arthritis, but broader improvements are needed with respect to treatment strategies, according to Dr. Iain McInnes.

Earlier diagnosis, appropriate therapies, and treating to target are among the topics he covered in a presentation on maximizing patient outcomes at the annual Perspectives in Rheumatic Diseases.

A recent study demonstrated that even a 6-month delay in the diagnosis of psoriatic arthritis is associated with worse long-term outcomes on several measures. In that study of 283 patients (Ann. Rheum. Dis. 2014 Feb. 13 [doi: 10.1136/annrheumdis-2013-204858]), the median lag time from disease onset to first rheumatological assessment was 1 year, with only 30% of patients being seen by a rheumatologist within 6 months.

Multiple stepwise regression analysis showed that late consulters had a greater risk of developing peripheral joint erosions (odds ratio, 4.25) and had worse Health Assessment Questionnaire scores (odds ratio, 2.2).

One finding that could help with earlier diagnosis is detection of early entheseal involvement, said Dr. McInnes, professor of medicine and director of the Institute of Infection, Immunity and Immunology at the University of Glasgow (Scotland).

Subclinical entheseal involvement appears to predict psoriatic arthritis in patients presenting with psoriasis, he said at the conference.

In one study, the mean Glasgow Ultrasound Enthesitis Scoring System (GUESS) score was 7.9 in patients with psoriasis, compared with 2.9 in controls, and in another study, thickness of the quadriceps tendon was a significant predictor of the development of psoriatic arthritis in those with psoriasis.

A key challenge in maximizing outcomes in psoriatic arthritis is that rheumatoid arthritis and psoriatic arthritis are typically treated as homogeneous for the purposes of drug development, but the two diseases have distinct clinical phenotypes and time course, tissue distribution, tissue cell/molecular features, genetic susceptibility, and probably impact of immune senescence.

In fact, while disease-modifying antirheumatic drugs are included in European League Against Rheumatsm (EULAR) treatment guidelines for psoriatic arthritis, the Methotrexate in Psoriatic Arthritis (MIPA) trial, a 6-month, double-blind, randomized, placebo-controlled trial of methotrexate, showed no benefit for key psoriatic arthritis endpoints at 3 and 6 months (Rheumatology 2012;51:1368-77).

Data on methotrexate combination therapy is limited, but existing clinical trials and registry data show no clear evidence of benefit. Methotrexate also has long-term toxicity issues.

In studies of patients who received anti–tumor necrosis factor therapy, 59%-69% of patients achieved 20% improvement (ACR 20 response), 37%-50% achieved 50% improvement (ACR 50 response), and up to 52% of patients achieved minimal disease activity at various time points. Also, radiographic progression was improved with anti-TNF therapy vs. placebo. However, TNF inhibitors lose efficacy over time in some patients, and are associated with an increased risk of infection.

Other disappointments or unmet needs in psoriatic arthritis are dichotomous skin and joint responses to biologics, lack of established predictors of response to biologics, lack of a cure, and difficulties in achieving sustained remission, Dr. McInnes said.

Future therapeutic options, including several drugs in development, include drugs that target cytokines and their receptors, such as ustekinumab, which targets IL-12/23; secukinumab and ixekizumab, which target IL-17; and brodalumab, which targets IL-17 receptor A. Other potential targets include IL-6 and the IL-6 receptor and IL-23 and the IL-23 receptor.

Studies of ustekinumab, for example, demonstrate beneficial effects on enthesitis, dactylitis, and modified van der Heijde-Sharp score.

Drugs that target intracellular signaling pathways are also being studied in psoriatic arthritis, including JAK family agents such as tofacitinib and phosphodiesterase inhibitors like apremilast.

As for strategies to improve outcomes, the Tight Control in Psoriatic Arthritis (TICOPA) study provided a rationale for treating to target. Current recommendations call for a target of remission or low disease activity.

The availability of highly effective biologics makes minimal level of disease activity a realistic treatment target, Dr. McInnes said.

The conference was held by Global Academy for Medical Education. Global Academy for Medical Education and this news organization are owned by Frontline Medical Communications.

Dr. McInnes reported receiving research/grant support from Pfizer, Bristol-Myers Squibb, AstraZeneca, and Novo Nordisk, and serving as a consultant to Novartis, Bristol-Myers Squibb, Pfizer, and Galapagos. He is a member of scientific advisory boards for AstraZeneca, Crescendo Bioscience, and Janssen Biotech.