Psoriasis

In late September 2014, the US Food and Drug Administration approved the medication apremilast for treatment of moderate to severe plaque psoriasis in adults who are candidates for phototherapy or systemic therapy. It was previously approved for psoriatic arthritis in March 2014. Its mechanism includes selective inhibition of phosphodiesterase 4, resulting in increased intracellular cyclic adenosine monophosphate levels, indirectly mediating production of inflammatory mediators in many cell types, namely decreasing tumor necrosis factor α and IL-23 and increasing IL-10. Orally dosed at 30 mg twice daily, safety and efficacy was determined via 2 multicenter, randomized, double-blind, placebo-controlled trials—ESTEEM 1 and ESTEEM 2 (N=1257)—that highlighted a PASI-75 (psoriasis area severity index) in 30% of patients in the first 4 months and up to 88% of patients with PASI-75 in the first year (J Am Acad Dermatol. 2014;70(suppl 1):AB164). Additionally, according to results presented at a recent European Academy of Dermatology and Venereology meeting in early October 2014, pruritus and difficult areas such as the scalp, palmoplantar area, and nails showed significant improvement at week 16 (P<.0001). The most common side effects were diarrhea, nausea, upper respiratory infection, and headache, which occurred most often in the first 2 weeks of therapy. The medication does not require routine laboratory monitoring; however, because weight loss is possible, it is recommended that weight should be periodically checked. There are no contraindications aside from hypersensitivity to the drug itself, and caution should be taken in patients with unstable depression, suicidal ideation, or severe renal impairment. It is pregnancy category C.

What’s the issue?

Because it is administered orally; is dually indicated for plaque psoriasis and psoriatic arthritis; and does not require laboratory monitoring, alcohol consumption restrictions, category X classification, or immunosuppressive infection or cancer risk, the window-shopping appeal of this drug seems attractive compared to the veteran and contemporary pharmaceutical army of psoriasis therapy. However, based on the ESTEEM studies, meager apremilast PASI scores are not blowing us away like those of biologic medications. At a time when the evolution of medications for psoriasis seems like a revolving door for new products highlighting new mechanisms in new pathways in even newer cells in relationship to inflammation, how will this drug fit in?

We want to know your views! Tell us what you think.

In late September 2014, the US Food and Drug Administration approved the medication apremilast for treatment of moderate to severe plaque psoriasis in adults who are candidates for phototherapy or systemic therapy. It was previously approved for psoriatic arthritis in March 2014. Its mechanism includes selective inhibition of phosphodiesterase 4, resulting in increased intracellular cyclic adenosine monophosphate levels, indirectly mediating production of inflammatory mediators in many cell types, namely decreasing tumor necrosis factor α and IL-23 and increasing IL-10. Orally dosed at 30 mg twice daily, safety and efficacy was determined via 2 multicenter, randomized, double-blind, placebo-controlled trials—ESTEEM 1 and ESTEEM 2 (N=1257)—that highlighted a PASI-75 (psoriasis area severity index) in 30% of patients in the first 4 months and up to 88% of patients with PASI-75 in the first year (J Am Acad Dermatol. 2014;70(suppl 1):AB164). Additionally, according to results presented at a recent European Academy of Dermatology and Venereology meeting in early October 2014, pruritus and difficult areas such as the scalp, palmoplantar area, and nails showed significant improvement at week 16 (P<.0001). The most common side effects were diarrhea, nausea, upper respiratory infection, and headache, which occurred most often in the first 2 weeks of therapy. The medication does not require routine laboratory monitoring; however, because weight loss is possible, it is recommended that weight should be periodically checked. There are no contraindications aside from hypersensitivity to the drug itself, and caution should be taken in patients with unstable depression, suicidal ideation, or severe renal impairment. It is pregnancy category C.

What’s the issue?

Because it is administered orally; is dually indicated for plaque psoriasis and psoriatic arthritis; and does not require laboratory monitoring, alcohol consumption restrictions, category X classification, or immunosuppressive infection or cancer risk, the window-shopping appeal of this drug seems attractive compared to the veteran and contemporary pharmaceutical army of psoriasis therapy. However, based on the ESTEEM studies, meager apremilast PASI scores are not blowing us away like those of biologic medications. At a time when the evolution of medications for psoriasis seems like a revolving door for new products highlighting new mechanisms in new pathways in even newer cells in relationship to inflammation, how will this drug fit in?

We want to know your views! Tell us what you think.

In late September 2014, the US Food and Drug Administration approved the medication apremilast for treatment of moderate to severe plaque psoriasis in adults who are candidates for phototherapy or systemic therapy. It was previously approved for psoriatic arthritis in March 2014. Its mechanism includes selective inhibition of phosphodiesterase 4, resulting in increased intracellular cyclic adenosine monophosphate levels, indirectly mediating production of inflammatory mediators in many cell types, namely decreasing tumor necrosis factor α and IL-23 and increasing IL-10. Orally dosed at 30 mg twice daily, safety and efficacy was determined via 2 multicenter, randomized, double-blind, placebo-controlled trials—ESTEEM 1 and ESTEEM 2 (N=1257)—that highlighted a PASI-75 (psoriasis area severity index) in 30% of patients in the first 4 months and up to 88% of patients with PASI-75 in the first year (J Am Acad Dermatol. 2014;70(suppl 1):AB164). Additionally, according to results presented at a recent European Academy of Dermatology and Venereology meeting in early October 2014, pruritus and difficult areas such as the scalp, palmoplantar area, and nails showed significant improvement at week 16 (P<.0001). The most common side effects were diarrhea, nausea, upper respiratory infection, and headache, which occurred most often in the first 2 weeks of therapy. The medication does not require routine laboratory monitoring; however, because weight loss is possible, it is recommended that weight should be periodically checked. There are no contraindications aside from hypersensitivity to the drug itself, and caution should be taken in patients with unstable depression, suicidal ideation, or severe renal impairment. It is pregnancy category C.

What’s the issue?

Because it is administered orally; is dually indicated for plaque psoriasis and psoriatic arthritis; and does not require laboratory monitoring, alcohol consumption restrictions, category X classification, or immunosuppressive infection or cancer risk, the window-shopping appeal of this drug seems attractive compared to the veteran and contemporary pharmaceutical army of psoriasis therapy. However, based on the ESTEEM studies, meager apremilast PASI scores are not blowing us away like those of biologic medications. At a time when the evolution of medications for psoriasis seems like a revolving door for new products highlighting new mechanisms in new pathways in even newer cells in relationship to inflammation, how will this drug fit in?

We want to know your views! Tell us what you think.

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.

[email protected]

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.

[email protected]

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.

[email protected]

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.

[email protected]

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.

[email protected]

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.

[email protected]

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.

[email protected]

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.

[email protected]

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.

[email protected]

NEWPORT BEACH, CALIF. – The approval of apremilast (Otezla) for the treatment of moderate to severe plaque psoriasis will make a significant impact on patient care, Dr. Alan Menter of Baylor University Medical Center, Dallas, Tex., said at Skin Disease Education Foundation’s Women’s & Pediatric Dermatology Seminar.

“I think where this drug is going to have a role is ... patients who are risk averse to needles, have contraindications to TNF-alpha agents ... patients who want a drug with minimal to no long-term side effects,” with the exception of the significant incidence of diarrhea within the early weeks of starting the drug, Dr. Menter explained. Clinicians should explain the risk of diarrhea to patients, and help them get through the first few months. The diarrhea “definitely does vanish with time,” he said. Overall, the risk of side effects is extremely low, he noted. “It is probably the safest drug we have approved for psoriasis today.”

SDEF and this news organization are owned by Frontline Medical Communications.

[email protected]

NEWPORT BEACH, CALIF. – The approval of apremilast (Otezla) for the treatment of moderate to severe plaque psoriasis will make a significant impact on patient care, Dr. Alan Menter of Baylor University Medical Center, Dallas, Tex., said at Skin Disease Education Foundation’s Women’s & Pediatric Dermatology Seminar.

“I think where this drug is going to have a role is ... patients who are risk averse to needles, have contraindications to TNF-alpha agents ... patients who want a drug with minimal to no long-term side effects,” with the exception of the significant incidence of diarrhea within the early weeks of starting the drug, Dr. Menter explained. Clinicians should explain the risk of diarrhea to patients, and help them get through the first few months. The diarrhea “definitely does vanish with time,” he said. Overall, the risk of side effects is extremely low, he noted. “It is probably the safest drug we have approved for psoriasis today.”

SDEF and this news organization are owned by Frontline Medical Communications.

[email protected]

NEWPORT BEACH, CALIF. – The approval of apremilast (Otezla) for the treatment of moderate to severe plaque psoriasis will make a significant impact on patient care, Dr. Alan Menter of Baylor University Medical Center, Dallas, Tex., said at Skin Disease Education Foundation’s Women’s & Pediatric Dermatology Seminar.

“I think where this drug is going to have a role is ... patients who are risk averse to needles, have contraindications to TNF-alpha agents ... patients who want a drug with minimal to no long-term side effects,” with the exception of the significant incidence of diarrhea within the early weeks of starting the drug, Dr. Menter explained. Clinicians should explain the risk of diarrhea to patients, and help them get through the first few months. The diarrhea “definitely does vanish with time,” he said. Overall, the risk of side effects is extremely low, he noted. “It is probably the safest drug we have approved for psoriasis today.”

SDEF and this news organization are owned by Frontline Medical Communications.

[email protected]

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.

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.

[email protected]

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.

[email protected]

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.

[email protected]

On Twitter @sherryboschert

While the availability of coupons can help defray out-of-pocket costs and improve access and adherence to high-cost specialty drugs, it may also result in higher costs to the health system.

Patients used drug coupons to pay for $21.2 million of $35.3 million in out-of-pocket costs, according to an analysis of 265,000 prescriptions worth $911 million in 2013. The coupons generally dropped a patient’s out-of-pocket costs to less than $250 per prescription, a point below which patients were “far less likely” to abandon prescriptions in cases of specialty anti-inflammatory drugs and treatments for multiple sclerosis (Health Affairs 2014;33:1761-9 [doi:10.1377/hlthaff.2014.0497]).

But while the use of coupons demonstrated that the lower cost led to lower prescription abandonment rates, it also allowed patients to circumvent cost-containment measures that pharmacy benefit managers employ.

© Photodisc / ThinkStockPhotos.com

“We found that drug coupons were extremely effective in lowering patients’ costs to less than $50 per prescription, thus eliminating the incentive to select a preferred drug,” wrote Catherine I. Starner, Pharm.D., senior health outcomes researcher at pharmacy benefit manager Prime Therapeutics, and her colleagues.

To control costs at the health system level, tighter controls could be placed on specialty drugs at the pharmacy benefit manager level, according to Dr. Starner and her colleagues. Such controls could include prior authorization or the use of step therapies,as well as excluding coverage of nonpreferred drugs. The latter strategy, however, could make drug access a problem, especially if physicians are not aware of an insurance plan taking these steps.

Excluding specialty drugs “makes the patient responsible for the entire cost of the drug,” the authors noted. “If prescribers are unaware of such exclusions, or if patients require specific therapies, such exclusions may impose considerable costs on patients” and potentially lead to access issues.

[email protected]

While the availability of coupons can help defray out-of-pocket costs and improve access and adherence to high-cost specialty drugs, it may also result in higher costs to the health system.

Patients used drug coupons to pay for $21.2 million of $35.3 million in out-of-pocket costs, according to an analysis of 265,000 prescriptions worth $911 million in 2013. The coupons generally dropped a patient’s out-of-pocket costs to less than $250 per prescription, a point below which patients were “far less likely” to abandon prescriptions in cases of specialty anti-inflammatory drugs and treatments for multiple sclerosis (Health Affairs 2014;33:1761-9 [doi:10.1377/hlthaff.2014.0497]).

But while the use of coupons demonstrated that the lower cost led to lower prescription abandonment rates, it also allowed patients to circumvent cost-containment measures that pharmacy benefit managers employ.

© Photodisc / ThinkStockPhotos.com

“We found that drug coupons were extremely effective in lowering patients’ costs to less than $50 per prescription, thus eliminating the incentive to select a preferred drug,” wrote Catherine I. Starner, Pharm.D., senior health outcomes researcher at pharmacy benefit manager Prime Therapeutics, and her colleagues.

To control costs at the health system level, tighter controls could be placed on specialty drugs at the pharmacy benefit manager level, according to Dr. Starner and her colleagues. Such controls could include prior authorization or the use of step therapies,as well as excluding coverage of nonpreferred drugs. The latter strategy, however, could make drug access a problem, especially if physicians are not aware of an insurance plan taking these steps.

Excluding specialty drugs “makes the patient responsible for the entire cost of the drug,” the authors noted. “If prescribers are unaware of such exclusions, or if patients require specific therapies, such exclusions may impose considerable costs on patients” and potentially lead to access issues.

[email protected]

While the availability of coupons can help defray out-of-pocket costs and improve access and adherence to high-cost specialty drugs, it may also result in higher costs to the health system.

Patients used drug coupons to pay for $21.2 million of $35.3 million in out-of-pocket costs, according to an analysis of 265,000 prescriptions worth $911 million in 2013. The coupons generally dropped a patient’s out-of-pocket costs to less than $250 per prescription, a point below which patients were “far less likely” to abandon prescriptions in cases of specialty anti-inflammatory drugs and treatments for multiple sclerosis (Health Affairs 2014;33:1761-9 [doi:10.1377/hlthaff.2014.0497]).

But while the use of coupons demonstrated that the lower cost led to lower prescription abandonment rates, it also allowed patients to circumvent cost-containment measures that pharmacy benefit managers employ.

© Photodisc / ThinkStockPhotos.com

“We found that drug coupons were extremely effective in lowering patients’ costs to less than $50 per prescription, thus eliminating the incentive to select a preferred drug,” wrote Catherine I. Starner, Pharm.D., senior health outcomes researcher at pharmacy benefit manager Prime Therapeutics, and her colleagues.

To control costs at the health system level, tighter controls could be placed on specialty drugs at the pharmacy benefit manager level, according to Dr. Starner and her colleagues. Such controls could include prior authorization or the use of step therapies,as well as excluding coverage of nonpreferred drugs. The latter strategy, however, could make drug access a problem, especially if physicians are not aware of an insurance plan taking these steps.

Excluding specialty drugs “makes the patient responsible for the entire cost of the drug,” the authors noted. “If prescribers are unaware of such exclusions, or if patients require specific therapies, such exclusions may impose considerable costs on patients” and potentially lead to access issues.

[email protected]

We are always conscious of the use of systemic medications in older patients, as they may have the potential for more toxicity. For dermatologists, use of systemic medications in psoriasis represents a large share of our total use. Theoretically, we are concerned that older patients may be more likely to develop serious infections and malignancies. Older psoriasis patients also represent a growing demographic, and they are underrepresented in clinical trials.

In an article published online on September 3, 2014, in the Journal of the European Academy of Dermatology and Venereology, Medina et al performed an analysis to evaluate the safety of systemic psoriasis therapy in patients older than 65 years compared to younger patients. Patients registered in Biobadaderm, a Spanish national registry of psoriasis patients treated with systemic therapy, were divided into 2 categories: elderly (≥65 years) and younger patients (<65 years). Rates of adverse events (AEs) were described by severity and type. The risks were compared in both groups, taking into account exposure to classic or biologic drugs using Cox regression.

In the overall study population, 175 (9.8%) of 1793 patients were elderly. The authors found that overall risk for AEs was not higher in elderly patients; the drug group–adjusted hazard ratio (HR) was 1.09 (95% confidence interval [CI], 0.93-1.3). However, serious AEs were more common in older patients, with a drug group–adjusted HR of 3.2 (95% CI, 2.0-5.1). Age-adjusted HR of all AEs was lower for patients exposed to biologics compared to classic drugs in the whole sample (HR, 0.7 [95% CI, 0.6-0.7]). Age did not seem to modify the effect of therapy (biologic vs classic) in the risk for AEs (likelihood ratio test for interaction: P=.12 for all AEs; P=.09 for serious AEs).

The authors concluded that serious AEs were more common in elderly patients. They argued, however, that these serious AEs might be related to other factors associated with this age group and not due to the treatment itself. Use of biologics was associated with lower risk for AEs in the whole group. There were no differences in this association between young and old. These results are reassuring, though uncontrolled confounding could not be excluded as an explanation for these findings. The power of the study to detect differences was low.

What’s the issue?

The results indicate that overall there is no increase in AEs in older patients. More data will need to be evaluated to see if the incidence of serious AEs is due to medication use or endogenous health factors. How do you approach the use of systemic medications in older patients?

We want to know your views! Tell us what you think.

We are always conscious of the use of systemic medications in older patients, as they may have the potential for more toxicity. For dermatologists, use of systemic medications in psoriasis represents a large share of our total use. Theoretically, we are concerned that older patients may be more likely to develop serious infections and malignancies. Older psoriasis patients also represent a growing demographic, and they are underrepresented in clinical trials.

In an article published online on September 3, 2014, in the Journal of the European Academy of Dermatology and Venereology, Medina et al performed an analysis to evaluate the safety of systemic psoriasis therapy in patients older than 65 years compared to younger patients. Patients registered in Biobadaderm, a Spanish national registry of psoriasis patients treated with systemic therapy, were divided into 2 categories: elderly (≥65 years) and younger patients (<65 years). Rates of adverse events (AEs) were described by severity and type. The risks were compared in both groups, taking into account exposure to classic or biologic drugs using Cox regression.

In the overall study population, 175 (9.8%) of 1793 patients were elderly. The authors found that overall risk for AEs was not higher in elderly patients; the drug group–adjusted hazard ratio (HR) was 1.09 (95% confidence interval [CI], 0.93-1.3). However, serious AEs were more common in older patients, with a drug group–adjusted HR of 3.2 (95% CI, 2.0-5.1). Age-adjusted HR of all AEs was lower for patients exposed to biologics compared to classic drugs in the whole sample (HR, 0.7 [95% CI, 0.6-0.7]). Age did not seem to modify the effect of therapy (biologic vs classic) in the risk for AEs (likelihood ratio test for interaction: P=.12 for all AEs; P=.09 for serious AEs).

The authors concluded that serious AEs were more common in elderly patients. They argued, however, that these serious AEs might be related to other factors associated with this age group and not due to the treatment itself. Use of biologics was associated with lower risk for AEs in the whole group. There were no differences in this association between young and old. These results are reassuring, though uncontrolled confounding could not be excluded as an explanation for these findings. The power of the study to detect differences was low.

What’s the issue?

The results indicate that overall there is no increase in AEs in older patients. More data will need to be evaluated to see if the incidence of serious AEs is due to medication use or endogenous health factors. How do you approach the use of systemic medications in older patients?

We want to know your views! Tell us what you think.

We are always conscious of the use of systemic medications in older patients, as they may have the potential for more toxicity. For dermatologists, use of systemic medications in psoriasis represents a large share of our total use. Theoretically, we are concerned that older patients may be more likely to develop serious infections and malignancies. Older psoriasis patients also represent a growing demographic, and they are underrepresented in clinical trials.

In an article published online on September 3, 2014, in the Journal of the European Academy of Dermatology and Venereology, Medina et al performed an analysis to evaluate the safety of systemic psoriasis therapy in patients older than 65 years compared to younger patients. Patients registered in Biobadaderm, a Spanish national registry of psoriasis patients treated with systemic therapy, were divided into 2 categories: elderly (≥65 years) and younger patients (<65 years). Rates of adverse events (AEs) were described by severity and type. The risks were compared in both groups, taking into account exposure to classic or biologic drugs using Cox regression.

In the overall study population, 175 (9.8%) of 1793 patients were elderly. The authors found that overall risk for AEs was not higher in elderly patients; the drug group–adjusted hazard ratio (HR) was 1.09 (95% confidence interval [CI], 0.93-1.3). However, serious AEs were more common in older patients, with a drug group–adjusted HR of 3.2 (95% CI, 2.0-5.1). Age-adjusted HR of all AEs was lower for patients exposed to biologics compared to classic drugs in the whole sample (HR, 0.7 [95% CI, 0.6-0.7]). Age did not seem to modify the effect of therapy (biologic vs classic) in the risk for AEs (likelihood ratio test for interaction: P=.12 for all AEs; P=.09 for serious AEs).

The authors concluded that serious AEs were more common in elderly patients. They argued, however, that these serious AEs might be related to other factors associated with this age group and not due to the treatment itself. Use of biologics was associated with lower risk for AEs in the whole group. There were no differences in this association between young and old. These results are reassuring, though uncontrolled confounding could not be excluded as an explanation for these findings. The power of the study to detect differences was low.

What’s the issue?

The results indicate that overall there is no increase in AEs in older patients. More data will need to be evaluated to see if the incidence of serious AEs is due to medication use or endogenous health factors. How do you approach the use of systemic medications in older patients?

We want to know your views! Tell us what you think.