Ankylosing spondylitis

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

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 One draft guidance and the legal restrictions referenced therein are relevant to physicians and pharmacists, as well as state-licensed pharmacies or federal facilities that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

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

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

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

[email protected]

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

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 One draft guidance and the legal restrictions referenced therein are relevant to physicians and pharmacists, as well as state-licensed pharmacies or federal facilities that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

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

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

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

[email protected]

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

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

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

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

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

[email protected]

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

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

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

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

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

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

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

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

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

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

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

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

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

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

[email protected]

On Twitter @mitchelzoler

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

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

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

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

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

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

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

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

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

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

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

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

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

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

[email protected]

On Twitter @mitchelzoler

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

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

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

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

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

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

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

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

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

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

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

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

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

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

[email protected]

On Twitter @mitchelzoler

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

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

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

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

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

[email protected]

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

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

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

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

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

[email protected]

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

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

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

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

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

[email protected]

The U.S. Food and Drug Administration has approved adalimumab for treatment of noninfectious intermediate, posterior, and panuveitis in adults, making it the only approved drug for the condition that is not a corticosteroid.

The approval marks the 10th approved indication for adalimumab (Humira) in the United States. It was recently approved for this indication in the European Union as well.

Patients on adalimumab had about half the risk of those on placebo to experience treatment failure (a combination of uveitis flare and decrease in visual acuity) in two pivotal phase III studies, VISUAL-I (hazard ratio, 0.5 for VISUAL-I; P less than .001) and VISUAL-II (HR, 0.57; P = .004). In the trials, patients were treated with an 80-mg loading dose of adalimumab at baseline, followed by a 40-mg subcutaneous injection at week 1 and then 40 mg every other week for up to 80 weeks.

“These approvals provide a valuable option for patients experiencing flare and vision impairment associated with this group of inflammatory diseases of the eye,” Glenn J. Jaffe, MD, of Duke University, Durham, N.C., said in an announcement from the manufacturer of adalimumab, AbbVie. “Data from the robust VISUAL clinical trial program demonstrate the value of Humira as a treatment option for patients with these serious diseases.”

[email protected]

The U.S. Food and Drug Administration has approved adalimumab for treatment of noninfectious intermediate, posterior, and panuveitis in adults, making it the only approved drug for the condition that is not a corticosteroid.

The approval marks the 10th approved indication for adalimumab (Humira) in the United States. It was recently approved for this indication in the European Union as well.

Patients on adalimumab had about half the risk of those on placebo to experience treatment failure (a combination of uveitis flare and decrease in visual acuity) in two pivotal phase III studies, VISUAL-I (hazard ratio, 0.5 for VISUAL-I; P less than .001) and VISUAL-II (HR, 0.57; P = .004). In the trials, patients were treated with an 80-mg loading dose of adalimumab at baseline, followed by a 40-mg subcutaneous injection at week 1 and then 40 mg every other week for up to 80 weeks.

“These approvals provide a valuable option for patients experiencing flare and vision impairment associated with this group of inflammatory diseases of the eye,” Glenn J. Jaffe, MD, of Duke University, Durham, N.C., said in an announcement from the manufacturer of adalimumab, AbbVie. “Data from the robust VISUAL clinical trial program demonstrate the value of Humira as a treatment option for patients with these serious diseases.”

[email protected]

The U.S. Food and Drug Administration has approved adalimumab for treatment of noninfectious intermediate, posterior, and panuveitis in adults, making it the only approved drug for the condition that is not a corticosteroid.

The approval marks the 10th approved indication for adalimumab (Humira) in the United States. It was recently approved for this indication in the European Union as well.

Patients on adalimumab had about half the risk of those on placebo to experience treatment failure (a combination of uveitis flare and decrease in visual acuity) in two pivotal phase III studies, VISUAL-I (hazard ratio, 0.5 for VISUAL-I; P less than .001) and VISUAL-II (HR, 0.57; P = .004). In the trials, patients were treated with an 80-mg loading dose of adalimumab at baseline, followed by a 40-mg subcutaneous injection at week 1 and then 40 mg every other week for up to 80 weeks.

“These approvals provide a valuable option for patients experiencing flare and vision impairment associated with this group of inflammatory diseases of the eye,” Glenn J. Jaffe, MD, of Duke University, Durham, N.C., said in an announcement from the manufacturer of adalimumab, AbbVie. “Data from the robust VISUAL clinical trial program demonstrate the value of Humira as a treatment option for patients with these serious diseases.”

[email protected]

Now that the interleukin-17 inhibitor secukinumab and tumor necrosis factor inhibitors are competing options for treatment of patients with ankylosing spondylitis, the companies that make those drugs must feel pressure to find some sort of advantage for their agents.

How else to explain the remarkable pair of similar post hoc analyses presented in June at the European Congress of Rheumatology in London? One of the analyses was funded by Novartis – the company that markets secukinumab (Cosentyx) – and included several Novartis employees as coauthors. The second study, presented immediately afterward in the main session at the meeting devoted to ankylosing spondylitis (AS) treatments, had backing from AbbVie, which markets adalimumab (Humira), the largest-selling tumor necrosis factor inhibitor worldwide, and had several AbbVie employees as coauthors.

Both analyses used a “matching adjusted indirect comparison,” a fairly new way to compare the performance of interventions studied in two totally independent trials by propensity matching patients from each of the two trials. It’s purportedly a way to make a legitimate comparison in the absence of head-to-head data.

Making the two reports even more surreal was their use of essentially the same data.

The first report came from Walter P. Maksymowych, MD, an AS clinician and researcher from the University of Alberta, who with his coauthors used data collected on secukinumab in the MEASURE 1 pivotal trial and on adalimumab in the ATLAS pivotal trial. He spent much of his presentation describing the methods behind the indirect comparison, and I don’t think I can be blamed for calling the results of this Novartis-sponsored analysis predictable: overall better performance by secukinumab, compared “indirectly” with adalimumab for clinical responses and patient quality of life.

Mitchel L. Zoler/Frontline Medical News

The second report, the one sponsored by AbbVie, came from Keith A. Betts, PhD, a biostatistician who works for the Analysis Group, an international consulting firm. He also used the ATLAS database as the source for adalimumab outcomes, and differed marginally from Dr. Maksymowych by taking data on secukinumab patients from both the MEASURE 1 and MEASURE 2 pivotal trials. Although Dr. Betts also used the matching adjusted indirect comparison approach and broadened his data source modestly, his results showed a distinctly different outcome: similar efficacy for the two drugs. Dr. Betts also included a cost efficacy analysis, and in this part adalimumab showed superior performance after he factored in the cost per responding AS patient.

During the combined discussion period following the two talks, both presenters defended the legitimacy of their approaches, although Dr. Maksymowych conceded that these indirect comparisons are “hypothesis generating rather than producing a definitive answer.” But a couple of active European AS researchers rose to comment from the floor and discredit the whole process.

“These two presentations show why I am not a proponent of indirect comparisons. The statistical models squeeze the data until they confess,” said Robert Landewé, MD, an AS specialist at the University of Amsterdam. “This is now a commercial rather than a scientific clash between two important drugs. I challenge these companies to perform a head-to-head trial. Indirect comparisons are not good,” he concluded, to a round of audience applause.

“There are so many methodological issues,” said Désirée van der Heijde, MD, another Dutch AS clinician and researcher who rose to critique both studies. “The only thing you can rely on is head-to-head trials.”

I later spoke with Dr. Maksymowych, and he expressed some pessimism about the prospects for a fully-powered, head-to-head trial of an interleukin-17 inhibitor and tumor necrosis factor inhibitor because it would need to enroll so many patients. “Randomized studies of active comparators need to be huge because it’s hard to show improvements when the response rates are high,” he said. Plus, he added, it isn’t entirely about a drug’s efficacy against AS spinal symptoms anyway.

“We also have to think about the impact of treatment on other aspects of this disease, such as psoriasis and colitis, as well as radiographic disease progression,” he said. These aspects of the activity of both classes of drugs have not received much study in AS patients until now.

In other words, the battle between treatment options for AS has just begun, and seems likely to be fought on many fronts.

[email protected]

On Twitter @mitchelzoler

Now that the interleukin-17 inhibitor secukinumab and tumor necrosis factor inhibitors are competing options for treatment of patients with ankylosing spondylitis, the companies that make those drugs must feel pressure to find some sort of advantage for their agents.

How else to explain the remarkable pair of similar post hoc analyses presented in June at the European Congress of Rheumatology in London? One of the analyses was funded by Novartis – the company that markets secukinumab (Cosentyx) – and included several Novartis employees as coauthors. The second study, presented immediately afterward in the main session at the meeting devoted to ankylosing spondylitis (AS) treatments, had backing from AbbVie, which markets adalimumab (Humira), the largest-selling tumor necrosis factor inhibitor worldwide, and had several AbbVie employees as coauthors.

Both analyses used a “matching adjusted indirect comparison,” a fairly new way to compare the performance of interventions studied in two totally independent trials by propensity matching patients from each of the two trials. It’s purportedly a way to make a legitimate comparison in the absence of head-to-head data.

Making the two reports even more surreal was their use of essentially the same data.

The first report came from Walter P. Maksymowych, MD, an AS clinician and researcher from the University of Alberta, who with his coauthors used data collected on secukinumab in the MEASURE 1 pivotal trial and on adalimumab in the ATLAS pivotal trial. He spent much of his presentation describing the methods behind the indirect comparison, and I don’t think I can be blamed for calling the results of this Novartis-sponsored analysis predictable: overall better performance by secukinumab, compared “indirectly” with adalimumab for clinical responses and patient quality of life.

Mitchel L. Zoler/Frontline Medical News

The second report, the one sponsored by AbbVie, came from Keith A. Betts, PhD, a biostatistician who works for the Analysis Group, an international consulting firm. He also used the ATLAS database as the source for adalimumab outcomes, and differed marginally from Dr. Maksymowych by taking data on secukinumab patients from both the MEASURE 1 and MEASURE 2 pivotal trials. Although Dr. Betts also used the matching adjusted indirect comparison approach and broadened his data source modestly, his results showed a distinctly different outcome: similar efficacy for the two drugs. Dr. Betts also included a cost efficacy analysis, and in this part adalimumab showed superior performance after he factored in the cost per responding AS patient.

During the combined discussion period following the two talks, both presenters defended the legitimacy of their approaches, although Dr. Maksymowych conceded that these indirect comparisons are “hypothesis generating rather than producing a definitive answer.” But a couple of active European AS researchers rose to comment from the floor and discredit the whole process.

“These two presentations show why I am not a proponent of indirect comparisons. The statistical models squeeze the data until they confess,” said Robert Landewé, MD, an AS specialist at the University of Amsterdam. “This is now a commercial rather than a scientific clash between two important drugs. I challenge these companies to perform a head-to-head trial. Indirect comparisons are not good,” he concluded, to a round of audience applause.

“There are so many methodological issues,” said Désirée van der Heijde, MD, another Dutch AS clinician and researcher who rose to critique both studies. “The only thing you can rely on is head-to-head trials.”

I later spoke with Dr. Maksymowych, and he expressed some pessimism about the prospects for a fully-powered, head-to-head trial of an interleukin-17 inhibitor and tumor necrosis factor inhibitor because it would need to enroll so many patients. “Randomized studies of active comparators need to be huge because it’s hard to show improvements when the response rates are high,” he said. Plus, he added, it isn’t entirely about a drug’s efficacy against AS spinal symptoms anyway.

“We also have to think about the impact of treatment on other aspects of this disease, such as psoriasis and colitis, as well as radiographic disease progression,” he said. These aspects of the activity of both classes of drugs have not received much study in AS patients until now.

In other words, the battle between treatment options for AS has just begun, and seems likely to be fought on many fronts.

[email protected]

On Twitter @mitchelzoler

Now that the interleukin-17 inhibitor secukinumab and tumor necrosis factor inhibitors are competing options for treatment of patients with ankylosing spondylitis, the companies that make those drugs must feel pressure to find some sort of advantage for their agents.

How else to explain the remarkable pair of similar post hoc analyses presented in June at the European Congress of Rheumatology in London? One of the analyses was funded by Novartis – the company that markets secukinumab (Cosentyx) – and included several Novartis employees as coauthors. The second study, presented immediately afterward in the main session at the meeting devoted to ankylosing spondylitis (AS) treatments, had backing from AbbVie, which markets adalimumab (Humira), the largest-selling tumor necrosis factor inhibitor worldwide, and had several AbbVie employees as coauthors.

Both analyses used a “matching adjusted indirect comparison,” a fairly new way to compare the performance of interventions studied in two totally independent trials by propensity matching patients from each of the two trials. It’s purportedly a way to make a legitimate comparison in the absence of head-to-head data.

Making the two reports even more surreal was their use of essentially the same data.

The first report came from Walter P. Maksymowych, MD, an AS clinician and researcher from the University of Alberta, who with his coauthors used data collected on secukinumab in the MEASURE 1 pivotal trial and on adalimumab in the ATLAS pivotal trial. He spent much of his presentation describing the methods behind the indirect comparison, and I don’t think I can be blamed for calling the results of this Novartis-sponsored analysis predictable: overall better performance by secukinumab, compared “indirectly” with adalimumab for clinical responses and patient quality of life.

Mitchel L. Zoler/Frontline Medical News

The second report, the one sponsored by AbbVie, came from Keith A. Betts, PhD, a biostatistician who works for the Analysis Group, an international consulting firm. He also used the ATLAS database as the source for adalimumab outcomes, and differed marginally from Dr. Maksymowych by taking data on secukinumab patients from both the MEASURE 1 and MEASURE 2 pivotal trials. Although Dr. Betts also used the matching adjusted indirect comparison approach and broadened his data source modestly, his results showed a distinctly different outcome: similar efficacy for the two drugs. Dr. Betts also included a cost efficacy analysis, and in this part adalimumab showed superior performance after he factored in the cost per responding AS patient.

During the combined discussion period following the two talks, both presenters defended the legitimacy of their approaches, although Dr. Maksymowych conceded that these indirect comparisons are “hypothesis generating rather than producing a definitive answer.” But a couple of active European AS researchers rose to comment from the floor and discredit the whole process.

“These two presentations show why I am not a proponent of indirect comparisons. The statistical models squeeze the data until they confess,” said Robert Landewé, MD, an AS specialist at the University of Amsterdam. “This is now a commercial rather than a scientific clash between two important drugs. I challenge these companies to perform a head-to-head trial. Indirect comparisons are not good,” he concluded, to a round of audience applause.

“There are so many methodological issues,” said Désirée van der Heijde, MD, another Dutch AS clinician and researcher who rose to critique both studies. “The only thing you can rely on is head-to-head trials.”

I later spoke with Dr. Maksymowych, and he expressed some pessimism about the prospects for a fully-powered, head-to-head trial of an interleukin-17 inhibitor and tumor necrosis factor inhibitor because it would need to enroll so many patients. “Randomized studies of active comparators need to be huge because it’s hard to show improvements when the response rates are high,” he said. Plus, he added, it isn’t entirely about a drug’s efficacy against AS spinal symptoms anyway.

“We also have to think about the impact of treatment on other aspects of this disease, such as psoriasis and colitis, as well as radiographic disease progression,” he said. These aspects of the activity of both classes of drugs have not received much study in AS patients until now.

In other words, the battle between treatment options for AS has just begun, and seems likely to be fought on many fronts.

[email protected]

On Twitter @mitchelzoler

LONDON – Patients with ankylosing spondylitis who remained on long-term treatment with a nonsteroidal anti-inflammatory drug and a tumor necrosis factor inhibitor had significantly less new spinal-bone formation in a cross-sectional analysis of a multicenter cohort of 527 U.S. patients.

A related analysis of the same cohort also showed significantly less ankylosing spondylitis (AS) progression as measured by radiographic progression among patients who received treatment with a tumor necrosis factor–alpha (TNF) inhibitor for 2.1-3.5 years regardless of their treatment with a nonsteroidal anti-inflammatory drug (NSAID), although this link trended to a stronger effect among the patients taking both, Lianne S. Gensler, MD, reported in a pair of posters at the European Congress of Rheumatology.

These finding suggest “there may be synergy between NSAIDs and TNF inhibitors [for slowing or preventing progression] in a select group of AS patients at high risk for progression,” said Dr. Gensler, a rheumatologist and director of the Ankylosing Spondylitis Clinic at the University of California, San Francisco.

But Dr. Gensler also cautioned that these findings are merely “hypothesis generating” and should not be used as a rationale to place or maintain AS patients on long-term treatment with an NSAID, a TNF inhibitor, or both drugs.

“You treat the disease burden. The message is absolutely not to always put AS patients on both types of drugs. When an AS patient is well controlled on a TNF inhibitor alone, I would not tell them to also take a NSAID,” she said in an interview. “This is only relevant for patients who require treatment with both drug classes because of their clinical status.”

As the list of treatment options for patients with AS grows – it now includes NSAIDs, TNF inhibitors, and the interleukin-17 inhibitor secukinumab (Cosentyx) – the impact of these agents on disease progression as assessed by radiography and new bone formation becomes a new dimension to start to consider in addition to the standard criterion of immediate clinical response, Dr. Gensler explained. AS progression “is another factor to think about as we decide on treatment strategies. There is growing evidence that long-term treatment with a tumor necrosis factor inhibitor and with a NSAID have potential roles in disease modification.” But the evidence is indirect, from cohort studies that make cause and effect assessments difficult because of possible unidentified confounding factors, she noted.

“There has never been a randomized, controlled trial examining the disease-modifying effects of a TNF inhibitor because you can’t keep patients on placebo for a long enough time to see this benefit,” Dr. Gensler said. It takes a long time to see progression in AS patients, she noted.

A prior cohort analysis run by Dr. Gensler and her associates found evidence for an effect of long-term treatment with a TNF inhibitor and reduced AS progression measured using the modified Stoke AS Spine Score (mSASSS), compared with AS patients not on a TNF inhibitor in a propensity-score matched analysis of 334 patients. A link between TNF inhibitor use and a discernible difference in mSASSS only occurred when patients were on TNF inhibitor treatment for at least 3.9 years (Arthritis Rheum. 2013 Oct;65[10]:2645-54). In addition, a separate report at the EULAR congress on 168 AS patients maintained on treatment with secukinumab for 2 years showed evidence for slowed progression of mSASSS scores, compared with historical controls as well as with similar patients who were not on secukinumab treatment for as long a period of time.

The new analysis reported by Dr. Gensler looked at 527 AS patients in the multicenter Prospective Study of Outcomes in AS cohort followed for a median of 3.7 years. Clinicians participating in this cohort saw patients every 6 months, and radiographic assessments by mSASSS and for new bone formation occurred every 2 years. At entry into the registry, about 57% of patients received a TNF inhibitor and about 63% received an NSAID, with a third on an NSAID only, 27% on a TNF inhibitor only, 30% on both drugs, and 10% receiving neither drug.

The analysis showed that among patients followed for 2.1-3.5 years, the fraction of patients on a TNF inhibitor who showed progression of their mSASSS was 77% lower than patients not on a TNF inhibitor, a statistically significant difference, Dr. Gensler reported. The researchers saw no statistically significant difference in mSASSS progression rates between the patients on a TNF inhibitor at baseline and those not on a TNF inhibitor at baseline among patients followed for 2 years and among those followed for more than 3.5 years, although the analysis did show nominally higher levels of response among TNF-inhibitor users followed for more than 3.5 years. Dr. Gensler speculated that one reason for the loss of a statistically significant difference during longer follow-up could be that fewer patients reached these levels of prolonged follow-up, making statistically significant differences harder to see. This analysis also showed a strong trend for less progression among the patients treated with an NSAID, a 51% relative reduction in mSASSS progression, compared with patients not taking an NSAID, but this relationship just missed statistical significance.

A second analysis by Dr. Gensler and her associates used data from the same cohort but focused on new bone formation during follow-up. This analysis again showed a statistically significant, 72% reduction in this outcome among patients taking a TNF inhibitor at baseline, compared with those not on a TNF inhibitor, when followed for 2.1-3.5 years, with no statistically significant relationship seen among patients followed for less or more time, Dr. Gensler reported. However, the results from this analysis also showed a statistically significant impact from NSAID treatment: Patients on a TNF inhibitor and an NSAID at baseline had 67% less new bone formation, compared with those who received a TNF inhibitor but were not on an NSAID at baseline.

Dr. Gensler has been a consultant to or investigator funded by AbbVie, Amgen, Janssen, Novartis, and UCB. The Prospective Study of Outcomes in Ankylosing Spondylitis receives no commercial support.

[email protected]

On Twitter @mitchelzoler

LONDON – Patients with ankylosing spondylitis who remained on long-term treatment with a nonsteroidal anti-inflammatory drug and a tumor necrosis factor inhibitor had significantly less new spinal-bone formation in a cross-sectional analysis of a multicenter cohort of 527 U.S. patients.

A related analysis of the same cohort also showed significantly less ankylosing spondylitis (AS) progression as measured by radiographic progression among patients who received treatment with a tumor necrosis factor–alpha (TNF) inhibitor for 2.1-3.5 years regardless of their treatment with a nonsteroidal anti-inflammatory drug (NSAID), although this link trended to a stronger effect among the patients taking both, Lianne S. Gensler, MD, reported in a pair of posters at the European Congress of Rheumatology.

These finding suggest “there may be synergy between NSAIDs and TNF inhibitors [for slowing or preventing progression] in a select group of AS patients at high risk for progression,” said Dr. Gensler, a rheumatologist and director of the Ankylosing Spondylitis Clinic at the University of California, San Francisco.

But Dr. Gensler also cautioned that these findings are merely “hypothesis generating” and should not be used as a rationale to place or maintain AS patients on long-term treatment with an NSAID, a TNF inhibitor, or both drugs.

“You treat the disease burden. The message is absolutely not to always put AS patients on both types of drugs. When an AS patient is well controlled on a TNF inhibitor alone, I would not tell them to also take a NSAID,” she said in an interview. “This is only relevant for patients who require treatment with both drug classes because of their clinical status.”

As the list of treatment options for patients with AS grows – it now includes NSAIDs, TNF inhibitors, and the interleukin-17 inhibitor secukinumab (Cosentyx) – the impact of these agents on disease progression as assessed by radiography and new bone formation becomes a new dimension to start to consider in addition to the standard criterion of immediate clinical response, Dr. Gensler explained. AS progression “is another factor to think about as we decide on treatment strategies. There is growing evidence that long-term treatment with a tumor necrosis factor inhibitor and with a NSAID have potential roles in disease modification.” But the evidence is indirect, from cohort studies that make cause and effect assessments difficult because of possible unidentified confounding factors, she noted.

“There has never been a randomized, controlled trial examining the disease-modifying effects of a TNF inhibitor because you can’t keep patients on placebo for a long enough time to see this benefit,” Dr. Gensler said. It takes a long time to see progression in AS patients, she noted.

A prior cohort analysis run by Dr. Gensler and her associates found evidence for an effect of long-term treatment with a TNF inhibitor and reduced AS progression measured using the modified Stoke AS Spine Score (mSASSS), compared with AS patients not on a TNF inhibitor in a propensity-score matched analysis of 334 patients. A link between TNF inhibitor use and a discernible difference in mSASSS only occurred when patients were on TNF inhibitor treatment for at least 3.9 years (Arthritis Rheum. 2013 Oct;65[10]:2645-54). In addition, a separate report at the EULAR congress on 168 AS patients maintained on treatment with secukinumab for 2 years showed evidence for slowed progression of mSASSS scores, compared with historical controls as well as with similar patients who were not on secukinumab treatment for as long a period of time.

The new analysis reported by Dr. Gensler looked at 527 AS patients in the multicenter Prospective Study of Outcomes in AS cohort followed for a median of 3.7 years. Clinicians participating in this cohort saw patients every 6 months, and radiographic assessments by mSASSS and for new bone formation occurred every 2 years. At entry into the registry, about 57% of patients received a TNF inhibitor and about 63% received an NSAID, with a third on an NSAID only, 27% on a TNF inhibitor only, 30% on both drugs, and 10% receiving neither drug.

The analysis showed that among patients followed for 2.1-3.5 years, the fraction of patients on a TNF inhibitor who showed progression of their mSASSS was 77% lower than patients not on a TNF inhibitor, a statistically significant difference, Dr. Gensler reported. The researchers saw no statistically significant difference in mSASSS progression rates between the patients on a TNF inhibitor at baseline and those not on a TNF inhibitor at baseline among patients followed for 2 years and among those followed for more than 3.5 years, although the analysis did show nominally higher levels of response among TNF-inhibitor users followed for more than 3.5 years. Dr. Gensler speculated that one reason for the loss of a statistically significant difference during longer follow-up could be that fewer patients reached these levels of prolonged follow-up, making statistically significant differences harder to see. This analysis also showed a strong trend for less progression among the patients treated with an NSAID, a 51% relative reduction in mSASSS progression, compared with patients not taking an NSAID, but this relationship just missed statistical significance.

A second analysis by Dr. Gensler and her associates used data from the same cohort but focused on new bone formation during follow-up. This analysis again showed a statistically significant, 72% reduction in this outcome among patients taking a TNF inhibitor at baseline, compared with those not on a TNF inhibitor, when followed for 2.1-3.5 years, with no statistically significant relationship seen among patients followed for less or more time, Dr. Gensler reported. However, the results from this analysis also showed a statistically significant impact from NSAID treatment: Patients on a TNF inhibitor and an NSAID at baseline had 67% less new bone formation, compared with those who received a TNF inhibitor but were not on an NSAID at baseline.

Dr. Gensler has been a consultant to or investigator funded by AbbVie, Amgen, Janssen, Novartis, and UCB. The Prospective Study of Outcomes in Ankylosing Spondylitis receives no commercial support.

[email protected]

On Twitter @mitchelzoler

LONDON – Patients with ankylosing spondylitis who remained on long-term treatment with a nonsteroidal anti-inflammatory drug and a tumor necrosis factor inhibitor had significantly less new spinal-bone formation in a cross-sectional analysis of a multicenter cohort of 527 U.S. patients.

A related analysis of the same cohort also showed significantly less ankylosing spondylitis (AS) progression as measured by radiographic progression among patients who received treatment with a tumor necrosis factor–alpha (TNF) inhibitor for 2.1-3.5 years regardless of their treatment with a nonsteroidal anti-inflammatory drug (NSAID), although this link trended to a stronger effect among the patients taking both, Lianne S. Gensler, MD, reported in a pair of posters at the European Congress of Rheumatology.

These finding suggest “there may be synergy between NSAIDs and TNF inhibitors [for slowing or preventing progression] in a select group of AS patients at high risk for progression,” said Dr. Gensler, a rheumatologist and director of the Ankylosing Spondylitis Clinic at the University of California, San Francisco.

But Dr. Gensler also cautioned that these findings are merely “hypothesis generating” and should not be used as a rationale to place or maintain AS patients on long-term treatment with an NSAID, a TNF inhibitor, or both drugs.

“You treat the disease burden. The message is absolutely not to always put AS patients on both types of drugs. When an AS patient is well controlled on a TNF inhibitor alone, I would not tell them to also take a NSAID,” she said in an interview. “This is only relevant for patients who require treatment with both drug classes because of their clinical status.”

As the list of treatment options for patients with AS grows – it now includes NSAIDs, TNF inhibitors, and the interleukin-17 inhibitor secukinumab (Cosentyx) – the impact of these agents on disease progression as assessed by radiography and new bone formation becomes a new dimension to start to consider in addition to the standard criterion of immediate clinical response, Dr. Gensler explained. AS progression “is another factor to think about as we decide on treatment strategies. There is growing evidence that long-term treatment with a tumor necrosis factor inhibitor and with a NSAID have potential roles in disease modification.” But the evidence is indirect, from cohort studies that make cause and effect assessments difficult because of possible unidentified confounding factors, she noted.

“There has never been a randomized, controlled trial examining the disease-modifying effects of a TNF inhibitor because you can’t keep patients on placebo for a long enough time to see this benefit,” Dr. Gensler said. It takes a long time to see progression in AS patients, she noted.

A prior cohort analysis run by Dr. Gensler and her associates found evidence for an effect of long-term treatment with a TNF inhibitor and reduced AS progression measured using the modified Stoke AS Spine Score (mSASSS), compared with AS patients not on a TNF inhibitor in a propensity-score matched analysis of 334 patients. A link between TNF inhibitor use and a discernible difference in mSASSS only occurred when patients were on TNF inhibitor treatment for at least 3.9 years (Arthritis Rheum. 2013 Oct;65[10]:2645-54). In addition, a separate report at the EULAR congress on 168 AS patients maintained on treatment with secukinumab for 2 years showed evidence for slowed progression of mSASSS scores, compared with historical controls as well as with similar patients who were not on secukinumab treatment for as long a period of time.

The new analysis reported by Dr. Gensler looked at 527 AS patients in the multicenter Prospective Study of Outcomes in AS cohort followed for a median of 3.7 years. Clinicians participating in this cohort saw patients every 6 months, and radiographic assessments by mSASSS and for new bone formation occurred every 2 years. At entry into the registry, about 57% of patients received a TNF inhibitor and about 63% received an NSAID, with a third on an NSAID only, 27% on a TNF inhibitor only, 30% on both drugs, and 10% receiving neither drug.

The analysis showed that among patients followed for 2.1-3.5 years, the fraction of patients on a TNF inhibitor who showed progression of their mSASSS was 77% lower than patients not on a TNF inhibitor, a statistically significant difference, Dr. Gensler reported. The researchers saw no statistically significant difference in mSASSS progression rates between the patients on a TNF inhibitor at baseline and those not on a TNF inhibitor at baseline among patients followed for 2 years and among those followed for more than 3.5 years, although the analysis did show nominally higher levels of response among TNF-inhibitor users followed for more than 3.5 years. Dr. Gensler speculated that one reason for the loss of a statistically significant difference during longer follow-up could be that fewer patients reached these levels of prolonged follow-up, making statistically significant differences harder to see. This analysis also showed a strong trend for less progression among the patients treated with an NSAID, a 51% relative reduction in mSASSS progression, compared with patients not taking an NSAID, but this relationship just missed statistical significance.

A second analysis by Dr. Gensler and her associates used data from the same cohort but focused on new bone formation during follow-up. This analysis again showed a statistically significant, 72% reduction in this outcome among patients taking a TNF inhibitor at baseline, compared with those not on a TNF inhibitor, when followed for 2.1-3.5 years, with no statistically significant relationship seen among patients followed for less or more time, Dr. Gensler reported. However, the results from this analysis also showed a statistically significant impact from NSAID treatment: Patients on a TNF inhibitor and an NSAID at baseline had 67% less new bone formation, compared with those who received a TNF inhibitor but were not on an NSAID at baseline.

Dr. Gensler has been a consultant to or investigator funded by AbbVie, Amgen, Janssen, Novartis, and UCB. The Prospective Study of Outcomes in Ankylosing Spondylitis receives no commercial support.

[email protected]

On Twitter @mitchelzoler

LONDON – Patients with ankylosing spondylitis who remained on long-term treatment with a nonsteroidal anti-inflammatory drug and a tumor necrosis factor inhibitor had significantly less new spinal-bone formation in a cross-sectional analysis of a multicenter cohort of 527 U.S. patients.

A related analysis of the same cohort also showed significantly less ankylosing spondylitis (AS) progression as measured by radiographic progression among patients who received treatment with a tumor necrosis factor–alpha (TNF) inhibitor for 2.1-3.5 years regardless of their treatment with a nonsteroidal anti-inflammatory drug (NSAID), although this link trended to a stronger effect among the patients taking both, Lianne S. Gensler, MD, reported in a pair of posters at the European Congress of Rheumatology.

These finding suggest “there may be synergy between NSAIDs and TNF inhibitors [for slowing or preventing progression] in a select group of AS patients at high risk for progression,” said Dr. Gensler, a rheumatologist and director of the Ankylosing Spondylitis Clinic at the University of California, San Francisco.

But Dr. Gensler also cautioned that these findings are merely “hypothesis generating” and should not be used as a rationale to place or maintain AS patients on long-term treatment with an NSAID, a TNF inhibitor, or both drugs.

“You treat the disease burden. The message is absolutely not to always put AS patients on both types of drugs. When an AS patient is well controlled on a TNF inhibitor alone, I would not tell them to also take a NSAID,” she said in an interview. “This is only relevant for patients who require treatment with both drug classes because of their clinical status.”

As the list of treatment options for patients with AS grows – it now includes NSAIDs, TNF inhibitors, and the interleukin-17 inhibitor secukinumab (Cosentyx) – the impact of these agents on disease progression as assessed by radiography and new bone formation becomes a new dimension to start to consider in addition to the standard criterion of immediate clinical response, Dr. Gensler explained. AS progression “is another factor to think about as we decide on treatment strategies. There is growing evidence that long-term treatment with a tumor necrosis factor inhibitor and with a NSAID have potential roles in disease modification.” But the evidence is indirect, from cohort studies that make cause and effect assessments difficult because of possible unidentified confounding factors, she noted.

“There has never been a randomized, controlled trial examining the disease-modifying effects of a TNF inhibitor because you can’t keep patients on placebo for a long enough time to see this benefit,” Dr. Gensler said. It takes a long time to see progression in AS patients, she noted.

A prior cohort analysis run by Dr. Gensler and her associates found evidence for an effect of long-term treatment with a TNF inhibitor and reduced AS progression measured using the modified Stoke AS Spine Score (mSASSS), compared with AS patients not on a TNF inhibitor in a propensity-score matched analysis of 334 patients. A link between TNF inhibitor use and a discernible difference in mSASSS only occurred when patients were on TNF inhibitor treatment for at least 3.9 years (Arthritis Rheum. 2013 Oct;65[10]:2645-54). In addition, a separate report at the EULAR congress on 168 AS patients maintained on treatment with secukinumab for 2 years showed evidence for slowed progression of mSASSS scores, compared with historical controls as well as with similar patients who were not on secukinumab treatment for as long a period of time.

The new analysis reported by Dr. Gensler looked at 527 AS patients in the multicenter Prospective Study of Outcomes in AS cohort followed for a median of 3.7 years. Clinicians participating in this cohort saw patients every 6 months, and radiographic assessments by mSASSS and for new bone formation occurred every 2 years. At entry into the registry, about 57% of patients received a TNF inhibitor and about 63% received an NSAID, with a third on an NSAID only, 27% on a TNF inhibitor only, 30% on both drugs, and 10% receiving neither drug.

The analysis showed that among patients followed for 2.1-3.5 years, the fraction of patients on a TNF inhibitor who showed progression of their mSASSS was 77% lower than patients not on a TNF inhibitor, a statistically significant difference, Dr. Gensler reported. The researchers saw no statistically significant difference in mSASSS progression rates between the patients on a TNF inhibitor at baseline and those not on a TNF inhibitor at baseline among patients followed for 2 years and among those followed for more than 3.5 years, although the analysis did show nominally higher levels of response among TNF-inhibitor users followed for more than 3.5 years. Dr. Gensler speculated that one reason for the loss of a statistically significant difference during longer follow-up could be that fewer patients reached these levels of prolonged follow-up, making statistically significant differences harder to see. This analysis also showed a strong trend for less progression among the patients treated with an NSAID, a 51% relative reduction in mSASSS progression, compared with patients not taking an NSAID, but this relationship just missed statistical significance.

A second analysis by Dr. Gensler and her associates used data from the same cohort but focused on new bone formation during follow-up. This analysis again showed a statistically significant, 72% reduction in this outcome among patients taking a TNF inhibitor at baseline, compared with those not on a TNF inhibitor, when followed for 2.1-3.5 years, with no statistically significant relationship seen among patients followed for less or more time, Dr. Gensler reported. However, the results from this analysis also showed a statistically significant impact from NSAID treatment: Patients on a TNF inhibitor and an NSAID at baseline had 67% less new bone formation, compared with those who received a TNF inhibitor but were not on an NSAID at baseline.

Dr. Gensler has been a consultant to or investigator funded by AbbVie, Amgen, Janssen, Novartis, and UCB. The Prospective Study of Outcomes in Ankylosing Spondylitis receives no commercial support.

[email protected]

On Twitter @mitchelzoler

LONDON – Patients with ankylosing spondylitis who remained on long-term treatment with a nonsteroidal anti-inflammatory drug and a tumor necrosis factor inhibitor had significantly less new spinal-bone formation in a cross-sectional analysis of a multicenter cohort of 527 U.S. patients.

A related analysis of the same cohort also showed significantly less ankylosing spondylitis (AS) progression as measured by radiographic progression among patients who received treatment with a tumor necrosis factor–alpha (TNF) inhibitor for 2.1-3.5 years regardless of their treatment with a nonsteroidal anti-inflammatory drug (NSAID), although this link trended to a stronger effect among the patients taking both, Lianne S. Gensler, MD, reported in a pair of posters at the European Congress of Rheumatology.

These finding suggest “there may be synergy between NSAIDs and TNF inhibitors [for slowing or preventing progression] in a select group of AS patients at high risk for progression,” said Dr. Gensler, a rheumatologist and director of the Ankylosing Spondylitis Clinic at the University of California, San Francisco.

But Dr. Gensler also cautioned that these findings are merely “hypothesis generating” and should not be used as a rationale to place or maintain AS patients on long-term treatment with an NSAID, a TNF inhibitor, or both drugs.

“You treat the disease burden. The message is absolutely not to always put AS patients on both types of drugs. When an AS patient is well controlled on a TNF inhibitor alone, I would not tell them to also take a NSAID,” she said in an interview. “This is only relevant for patients who require treatment with both drug classes because of their clinical status.”

As the list of treatment options for patients with AS grows – it now includes NSAIDs, TNF inhibitors, and the interleukin-17 inhibitor secukinumab (Cosentyx) – the impact of these agents on disease progression as assessed by radiography and new bone formation becomes a new dimension to start to consider in addition to the standard criterion of immediate clinical response, Dr. Gensler explained. AS progression “is another factor to think about as we decide on treatment strategies. There is growing evidence that long-term treatment with a tumor necrosis factor inhibitor and with a NSAID have potential roles in disease modification.” But the evidence is indirect, from cohort studies that make cause and effect assessments difficult because of possible unidentified confounding factors, she noted.

“There has never been a randomized, controlled trial examining the disease-modifying effects of a TNF inhibitor because you can’t keep patients on placebo for a long enough time to see this benefit,” Dr. Gensler said. It takes a long time to see progression in AS patients, she noted.

A prior cohort analysis run by Dr. Gensler and her associates found evidence for an effect of long-term treatment with a TNF inhibitor and reduced AS progression measured using the modified Stoke AS Spine Score (mSASSS), compared with AS patients not on a TNF inhibitor in a propensity-score matched analysis of 334 patients. A link between TNF inhibitor use and a discernible difference in mSASSS only occurred when patients were on TNF inhibitor treatment for at least 3.9 years (Arthritis Rheum. 2013 Oct;65[10]:2645-54). In addition, a separate report at the EULAR congress on 168 AS patients maintained on treatment with secukinumab for 2 years showed evidence for slowed progression of mSASSS scores, compared with historical controls as well as with similar patients who were not on secukinumab treatment for as long a period of time.

The new analysis reported by Dr. Gensler looked at 527 AS patients in the multicenter Prospective Study of Outcomes in AS cohort followed for a median of 3.7 years. Clinicians participating in this cohort saw patients every 6 months, and radiographic assessments by mSASSS and for new bone formation occurred every 2 years. At entry into the registry, about 57% of patients received a TNF inhibitor and about 63% received an NSAID, with a third on an NSAID only, 27% on a TNF inhibitor only, 30% on both drugs, and 10% receiving neither drug.

The analysis showed that among patients followed for 2.1-3.5 years, the fraction of patients on a TNF inhibitor who showed progression of their mSASSS was 77% lower than patients not on a TNF inhibitor, a statistically significant difference, Dr. Gensler reported. The researchers saw no statistically significant difference in mSASSS progression rates between the patients on a TNF inhibitor at baseline and those not on a TNF inhibitor at baseline among patients followed for 2 years and among those followed for more than 3.5 years, although the analysis did show nominally higher levels of response among TNF-inhibitor users followed for more than 3.5 years. Dr. Gensler speculated that one reason for the loss of a statistically significant difference during longer follow-up could be that fewer patients reached these levels of prolonged follow-up, making statistically significant differences harder to see. This analysis also showed a strong trend for less progression among the patients treated with an NSAID, a 51% relative reduction in mSASSS progression, compared with patients not taking an NSAID, but this relationship just missed statistical significance.

A second analysis by Dr. Gensler and her associates used data from the same cohort but focused on new bone formation during follow-up. This analysis again showed a statistically significant, 72% reduction in this outcome among patients taking a TNF inhibitor at baseline, compared with those not on a TNF inhibitor, when followed for 2.1-3.5 years, with no statistically significant relationship seen among patients followed for less or more time, Dr. Gensler reported. However, the results from this analysis also showed a statistically significant impact from NSAID treatment: Patients on a TNF inhibitor and an NSAID at baseline had 67% less new bone formation, compared with those who received a TNF inhibitor but were not on an NSAID at baseline.

Dr. Gensler has been a consultant to or investigator funded by AbbVie, Amgen, Janssen, Novartis, and UCB. The Prospective Study of Outcomes in Ankylosing Spondylitis receives no commercial support.

[email protected]

On Twitter @mitchelzoler

LONDON – Patients with ankylosing spondylitis who remained on long-term treatment with a nonsteroidal anti-inflammatory drug and a tumor necrosis factor inhibitor had significantly less new spinal-bone formation in a cross-sectional analysis of a multicenter cohort of 527 U.S. patients.

A related analysis of the same cohort also showed significantly less ankylosing spondylitis (AS) progression as measured by radiographic progression among patients who received treatment with a tumor necrosis factor–alpha (TNF) inhibitor for 2.1-3.5 years regardless of their treatment with a nonsteroidal anti-inflammatory drug (NSAID), although this link trended to a stronger effect among the patients taking both, Lianne S. Gensler, MD, reported in a pair of posters at the European Congress of Rheumatology.

These finding suggest “there may be synergy between NSAIDs and TNF inhibitors [for slowing or preventing progression] in a select group of AS patients at high risk for progression,” said Dr. Gensler, a rheumatologist and director of the Ankylosing Spondylitis Clinic at the University of California, San Francisco.

But Dr. Gensler also cautioned that these findings are merely “hypothesis generating” and should not be used as a rationale to place or maintain AS patients on long-term treatment with an NSAID, a TNF inhibitor, or both drugs.

“You treat the disease burden. The message is absolutely not to always put AS patients on both types of drugs. When an AS patient is well controlled on a TNF inhibitor alone, I would not tell them to also take a NSAID,” she said in an interview. “This is only relevant for patients who require treatment with both drug classes because of their clinical status.”

As the list of treatment options for patients with AS grows – it now includes NSAIDs, TNF inhibitors, and the interleukin-17 inhibitor secukinumab (Cosentyx) – the impact of these agents on disease progression as assessed by radiography and new bone formation becomes a new dimension to start to consider in addition to the standard criterion of immediate clinical response, Dr. Gensler explained. AS progression “is another factor to think about as we decide on treatment strategies. There is growing evidence that long-term treatment with a tumor necrosis factor inhibitor and with a NSAID have potential roles in disease modification.” But the evidence is indirect, from cohort studies that make cause and effect assessments difficult because of possible unidentified confounding factors, she noted.

“There has never been a randomized, controlled trial examining the disease-modifying effects of a TNF inhibitor because you can’t keep patients on placebo for a long enough time to see this benefit,” Dr. Gensler said. It takes a long time to see progression in AS patients, she noted.

A prior cohort analysis run by Dr. Gensler and her associates found evidence for an effect of long-term treatment with a TNF inhibitor and reduced AS progression measured using the modified Stoke AS Spine Score (mSASSS), compared with AS patients not on a TNF inhibitor in a propensity-score matched analysis of 334 patients. A link between TNF inhibitor use and a discernible difference in mSASSS only occurred when patients were on TNF inhibitor treatment for at least 3.9 years (Arthritis Rheum. 2013 Oct;65[10]:2645-54). In addition, a separate report at the EULAR congress on 168 AS patients maintained on treatment with secukinumab for 2 years showed evidence for slowed progression of mSASSS scores, compared with historical controls as well as with similar patients who were not on secukinumab treatment for as long a period of time.

The new analysis reported by Dr. Gensler looked at 527 AS patients in the multicenter Prospective Study of Outcomes in AS cohort followed for a median of 3.7 years. Clinicians participating in this cohort saw patients every 6 months, and radiographic assessments by mSASSS and for new bone formation occurred every 2 years. At entry into the registry, about 57% of patients received a TNF inhibitor and about 63% received an NSAID, with a third on an NSAID only, 27% on a TNF inhibitor only, 30% on both drugs, and 10% receiving neither drug.

The analysis showed that among patients followed for 2.1-3.5 years, the fraction of patients on a TNF inhibitor who showed progression of their mSASSS was 77% lower than patients not on a TNF inhibitor, a statistically significant difference, Dr. Gensler reported. The researchers saw no statistically significant difference in mSASSS progression rates between the patients on a TNF inhibitor at baseline and those not on a TNF inhibitor at baseline among patients followed for 2 years and among those followed for more than 3.5 years, although the analysis did show nominally higher levels of response among TNF-inhibitor users followed for more than 3.5 years. Dr. Gensler speculated that one reason for the loss of a statistically significant difference during longer follow-up could be that fewer patients reached these levels of prolonged follow-up, making statistically significant differences harder to see. This analysis also showed a strong trend for less progression among the patients treated with an NSAID, a 51% relative reduction in mSASSS progression, compared with patients not taking an NSAID, but this relationship just missed statistical significance.

A second analysis by Dr. Gensler and her associates used data from the same cohort but focused on new bone formation during follow-up. This analysis again showed a statistically significant, 72% reduction in this outcome among patients taking a TNF inhibitor at baseline, compared with those not on a TNF inhibitor, when followed for 2.1-3.5 years, with no statistically significant relationship seen among patients followed for less or more time, Dr. Gensler reported. However, the results from this analysis also showed a statistically significant impact from NSAID treatment: Patients on a TNF inhibitor and an NSAID at baseline had 67% less new bone formation, compared with those who received a TNF inhibitor but were not on an NSAID at baseline.

Dr. Gensler has been a consultant to or investigator funded by AbbVie, Amgen, Janssen, Novartis, and UCB. The Prospective Study of Outcomes in Ankylosing Spondylitis receives no commercial support.

[email protected]

On Twitter @mitchelzoler

LONDON – The option of treating axial spondyloarthritis with an interleukin-17 inhibitor has become an officially recommended option for the first time in a new update to management recommendations for this disease released by a task force assembled jointly by the Assessment of SpondyloArthritis International Society and the European League Against Rheumatism.

The update replaces recommendations last released by the two groups for managing patients with ankylosing spondylitis in 2010 (Ann Rheum Dis. 2011 June;70[6]:896-904), as well as the prior recommendations from the two organizations for using tumor necrosis factor (TNF) inhibitors on these patients (Ann Rheum Dis. 2011 June;70[6]:905-8). The new update also broadens the disease spectrum from ankylosing spondylitis to axial spondyloarthritis (SpA).

Mitchel L. Zoler/Frontline Medical News

The latest recommendations continue to place nonsteroidal anti-inflammatory drugs (NSAIDs) as first-line pharmacotherapy for patients with axial SpA to control pain and stiffness, and continue to place treatment with a biological disease modifying antirheumatic drug (DMARD) – identified in the recommendations as most typically a TNF inhibitor by current practice – as second-line treatment after NSAIDs. The recommendations specify that initiation of a biological DMARD should target patients who have both failed treatment with at least two different NSAIDs over the course of at least 4 weeks of treatment, and who have active disease documented by either of two standard measures of disease activity in patients with axial SpA: either a score of at least 2.1 on the ankylosing spondylitis disease activity score (ASDAS) or a score of at least 4 on the Bath ankylosing spondylitis disease activity index (BASDAI).

Incorporation of the ASDAS as a potential alternative to the BASDAI for assessing disease activity in these patients is another new feature of these recommendations, noted Dr. Désirée van der Heijde, convenor of the update task force, who presented the new recommendations at the European Congress of Rheumatology.

The new recommendations place use of an interleukin (IL)-17 inhibitor as a third-line management option, for patients who fail to adequately respond to a first TNF inhibitor, and they also say that an alternative to starting an IL-17 inhibitor at this stage of management is to instead try treatment with a second type of TNF inhibitor. The IL-17 inhibitor class includes secukinumab (Cosentyx), which received approval from the Food and Drug Administration for treating active ankylosing spondylitis in January 2016, and which also has approval for the same indication from the European Medicines Agency.

The updated recommendations leave unchanged from the prior version advice to use biological DMARDs only after failure of other treatments, as well as advocacy of nondrug therapy with regular exercise, smoking cessation, and physical therapy when appropriate as the very first therapeutic step to take, before even starting a NSAID regimen. For patients with axial SpA who have peripheral arthritis, the recommendations say that clinicians can consider treatment with a local injection of a glucocorticoid, and a treatment course with sulfasalazine. The recommendations do not endorse treatment with a conventional, synthetic DMARD for patients with purely axial disease, and they also recommend against long-term treatment with a systemic corticosteroid. The update calls analgesics contraindicated.

Another new feature of the updated recommendations is endorsement of treating axial SpA patients to a predefined treatment target, although the recommendations left the nature of that target undefined and is something for the treating clinician to discuss and tailor to each patient individually, said Dr. van der Heijde, professor of rheumatology at Leiden University Medical Center in The Netherlands. The update also introduces for the first time the recommendation to consider tapering down treatment with a biological DMARD for patients who achieve remission.

Dr. van der Heijde said that she has been a consultant to 17 drug companies.

[email protected]

On Twitter @mitchelzoler

LONDON – The option of treating axial spondyloarthritis with an interleukin-17 inhibitor has become an officially recommended option for the first time in a new update to management recommendations for this disease released by a task force assembled jointly by the Assessment of SpondyloArthritis International Society and the European League Against Rheumatism.

The update replaces recommendations last released by the two groups for managing patients with ankylosing spondylitis in 2010 (Ann Rheum Dis. 2011 June;70[6]:896-904), as well as the prior recommendations from the two organizations for using tumor necrosis factor (TNF) inhibitors on these patients (Ann Rheum Dis. 2011 June;70[6]:905-8). The new update also broadens the disease spectrum from ankylosing spondylitis to axial spondyloarthritis (SpA).

Mitchel L. Zoler/Frontline Medical News

The latest recommendations continue to place nonsteroidal anti-inflammatory drugs (NSAIDs) as first-line pharmacotherapy for patients with axial SpA to control pain and stiffness, and continue to place treatment with a biological disease modifying antirheumatic drug (DMARD) – identified in the recommendations as most typically a TNF inhibitor by current practice – as second-line treatment after NSAIDs. The recommendations specify that initiation of a biological DMARD should target patients who have both failed treatment with at least two different NSAIDs over the course of at least 4 weeks of treatment, and who have active disease documented by either of two standard measures of disease activity in patients with axial SpA: either a score of at least 2.1 on the ankylosing spondylitis disease activity score (ASDAS) or a score of at least 4 on the Bath ankylosing spondylitis disease activity index (BASDAI).

Incorporation of the ASDAS as a potential alternative to the BASDAI for assessing disease activity in these patients is another new feature of these recommendations, noted Dr. Désirée van der Heijde, convenor of the update task force, who presented the new recommendations at the European Congress of Rheumatology.

The new recommendations place use of an interleukin (IL)-17 inhibitor as a third-line management option, for patients who fail to adequately respond to a first TNF inhibitor, and they also say that an alternative to starting an IL-17 inhibitor at this stage of management is to instead try treatment with a second type of TNF inhibitor. The IL-17 inhibitor class includes secukinumab (Cosentyx), which received approval from the Food and Drug Administration for treating active ankylosing spondylitis in January 2016, and which also has approval for the same indication from the European Medicines Agency.

The updated recommendations leave unchanged from the prior version advice to use biological DMARDs only after failure of other treatments, as well as advocacy of nondrug therapy with regular exercise, smoking cessation, and physical therapy when appropriate as the very first therapeutic step to take, before even starting a NSAID regimen. For patients with axial SpA who have peripheral arthritis, the recommendations say that clinicians can consider treatment with a local injection of a glucocorticoid, and a treatment course with sulfasalazine. The recommendations do not endorse treatment with a conventional, synthetic DMARD for patients with purely axial disease, and they also recommend against long-term treatment with a systemic corticosteroid. The update calls analgesics contraindicated.

Another new feature of the updated recommendations is endorsement of treating axial SpA patients to a predefined treatment target, although the recommendations left the nature of that target undefined and is something for the treating clinician to discuss and tailor to each patient individually, said Dr. van der Heijde, professor of rheumatology at Leiden University Medical Center in The Netherlands. The update also introduces for the first time the recommendation to consider tapering down treatment with a biological DMARD for patients who achieve remission.

Dr. van der Heijde said that she has been a consultant to 17 drug companies.

[email protected]

On Twitter @mitchelzoler

LONDON – The option of treating axial spondyloarthritis with an interleukin-17 inhibitor has become an officially recommended option for the first time in a new update to management recommendations for this disease released by a task force assembled jointly by the Assessment of SpondyloArthritis International Society and the European League Against Rheumatism.

The update replaces recommendations last released by the two groups for managing patients with ankylosing spondylitis in 2010 (Ann Rheum Dis. 2011 June;70[6]:896-904), as well as the prior recommendations from the two organizations for using tumor necrosis factor (TNF) inhibitors on these patients (Ann Rheum Dis. 2011 June;70[6]:905-8). The new update also broadens the disease spectrum from ankylosing spondylitis to axial spondyloarthritis (SpA).

Mitchel L. Zoler/Frontline Medical News

The latest recommendations continue to place nonsteroidal anti-inflammatory drugs (NSAIDs) as first-line pharmacotherapy for patients with axial SpA to control pain and stiffness, and continue to place treatment with a biological disease modifying antirheumatic drug (DMARD) – identified in the recommendations as most typically a TNF inhibitor by current practice – as second-line treatment after NSAIDs. The recommendations specify that initiation of a biological DMARD should target patients who have both failed treatment with at least two different NSAIDs over the course of at least 4 weeks of treatment, and who have active disease documented by either of two standard measures of disease activity in patients with axial SpA: either a score of at least 2.1 on the ankylosing spondylitis disease activity score (ASDAS) or a score of at least 4 on the Bath ankylosing spondylitis disease activity index (BASDAI).

Incorporation of the ASDAS as a potential alternative to the BASDAI for assessing disease activity in these patients is another new feature of these recommendations, noted Dr. Désirée van der Heijde, convenor of the update task force, who presented the new recommendations at the European Congress of Rheumatology.

The new recommendations place use of an interleukin (IL)-17 inhibitor as a third-line management option, for patients who fail to adequately respond to a first TNF inhibitor, and they also say that an alternative to starting an IL-17 inhibitor at this stage of management is to instead try treatment with a second type of TNF inhibitor. The IL-17 inhibitor class includes secukinumab (Cosentyx), which received approval from the Food and Drug Administration for treating active ankylosing spondylitis in January 2016, and which also has approval for the same indication from the European Medicines Agency.

The updated recommendations leave unchanged from the prior version advice to use biological DMARDs only after failure of other treatments, as well as advocacy of nondrug therapy with regular exercise, smoking cessation, and physical therapy when appropriate as the very first therapeutic step to take, before even starting a NSAID regimen. For patients with axial SpA who have peripheral arthritis, the recommendations say that clinicians can consider treatment with a local injection of a glucocorticoid, and a treatment course with sulfasalazine. The recommendations do not endorse treatment with a conventional, synthetic DMARD for patients with purely axial disease, and they also recommend against long-term treatment with a systemic corticosteroid. The update calls analgesics contraindicated.

Another new feature of the updated recommendations is endorsement of treating axial SpA patients to a predefined treatment target, although the recommendations left the nature of that target undefined and is something for the treating clinician to discuss and tailor to each patient individually, said Dr. van der Heijde, professor of rheumatology at Leiden University Medical Center in The Netherlands. The update also introduces for the first time the recommendation to consider tapering down treatment with a biological DMARD for patients who achieve remission.

Dr. van der Heijde said that she has been a consultant to 17 drug companies.

[email protected]

On Twitter @mitchelzoler

LONDON – Long-term treatment with the interleukin 17A inhibitor secukinumab showed suggestive evidence of inhibiting structural progression of spinal disease in 168 patients with ankylosing spondylitis, the first time any evidence for an effect like this has been seen with a biologic drug or any other agent used to treat ankylosing spondylitis.

However, the effect occurred in uncontrolled, 2-year open-label treatment of patients originally enrolled in one of the secukinumab pivotal trials, and the analysis did not include comparison against a historical control group, caveats that demand confirmation of this effect in additional studies, Dr. Jürgen Braun said at the European Congress of Rheumatology.

Mitchel L. Zoler/Frontline Medical News

In a second, unrelated study, the oral Janus kinase inhibitor tofacitinib showed promising efficacy for controlling clinical symptoms in patients with active ankylosing spondylitis (AS) during 12 weeks of treatment in a placebo-controlled, dose-ranging phase II study.

The open-label secukinumab extension study involved patients who had been enrolled in the MEASURE 1 study, one of the pivotal trials that had established secukinumab as safe and effective for improving the clinical status of patients with active AS. The primary endpoint of MEASURE 1 had been the percentage of patients achieving at least a 20% improvement in their Assessment of Spondyloarthritis international Society (ASAS20) response after 16 weeks of treatment (New Engl J Med. 2015 Dec 24;373[26]:2534-48).

Based in part on these data the Food and Drug Administration approved secukinumab (Cosentyx) for the treatment of ankylosing spondylitis in January 2016. The new data reported by Dr. Braun assessed the level of spinal pathology in a subgroup of the MEASURE 1 patients when measured by radiography using the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) at baseline and after 104 weeks on secukinumab treatment.

Patients in MEASURE 1 who began on active treatment received 10 mg/kg intravenous secukinumab for 4 weeks, followed by subcutaneous dosages of either 75 mg or 150 mg every 4 weeks for 104 weeks. His analysis also included some patients who entered MEASURE 1 in the placebo group and then switched to open-label, subcutaneous secukinumab treatment after 16 or 24 weeks on placebo.

Analysis of 168 patients who started on intravenous secukinumab and later received any subcutaneous secukinumab treatment out to 104 weeks showed an average increase in mSASSS of 0.30 after 104 weeks when compared against their baseline scores, reported Dr. Braun, professor and medical director of the Ruhr Rheumatology Center of the University of Bochum, Germany.

Among an additional 89 patients who began in the placebo group and then switched to subcutaneous secukinumab, the average change in mSASSS from baseline to 104 weeks was 0.54. By comparison, Dr. Braun noted that AS patients treated with a tumor necrosis factor inhibitor have shown 2-year progression in their mSASSS of about 0.8-0.9, and AS patients not treated with an active biologic drug have shown 2-year mSASSS progression of about 1.0.

A second analysis of the data reported by Dr. Braun showed that among the 168 patients treated for the full 104 weeks with secukinumab about 80% showed no mSASSS progression, but about 20% did have some level of detectable mSASSS progression.

The phase II study of tofacitinib (Xeljanz) randomized 208 patients with active AS to either tofacitinib at daily dosages of 2 mg bid, 5 mg bid, 10 mg bid, or placebo. The study’s primary endpoint was their ASAS20 response after 12 weeks that underwent a Bayesian Emax model analysis to estimate incremental efficacy when compared against placebo.

The primary efficacy analysis showed the greatest EmaxASAS20 response among patients treated with 5 mg bid daily, 63%, which was about 23% above the placebo level, reportedDr. Désirée van der Heijde, professor of rheumatology at the Leiden University Medical Center, The Netherlands. The absolute ASAS20 response rate of the 52 patients randomized to this tofacitinib dosage was about 81%, about 40% higher than the response rate seen in the 51 patients in the placebo arm.

All dosages of tofacitinib tested were well tolerated, with safety data similar to what has previously been shown for tofacitinib, a drug that has Food and Drug Administration approval for treating rheumatoid arthritis.

[email protected]

On Twitter @mitchelzoler

LONDON – Long-term treatment with the interleukin 17A inhibitor secukinumab showed suggestive evidence of inhibiting structural progression of spinal disease in 168 patients with ankylosing spondylitis, the first time any evidence for an effect like this has been seen with a biologic drug or any other agent used to treat ankylosing spondylitis.

However, the effect occurred in uncontrolled, 2-year open-label treatment of patients originally enrolled in one of the secukinumab pivotal trials, and the analysis did not include comparison against a historical control group, caveats that demand confirmation of this effect in additional studies, Dr. Jürgen Braun said at the European Congress of Rheumatology.

Mitchel L. Zoler/Frontline Medical News

In a second, unrelated study, the oral Janus kinase inhibitor tofacitinib showed promising efficacy for controlling clinical symptoms in patients with active ankylosing spondylitis (AS) during 12 weeks of treatment in a placebo-controlled, dose-ranging phase II study.

The open-label secukinumab extension study involved patients who had been enrolled in the MEASURE 1 study, one of the pivotal trials that had established secukinumab as safe and effective for improving the clinical status of patients with active AS. The primary endpoint of MEASURE 1 had been the percentage of patients achieving at least a 20% improvement in their Assessment of Spondyloarthritis international Society (ASAS20) response after 16 weeks of treatment (New Engl J Med. 2015 Dec 24;373[26]:2534-48).

Based in part on these data the Food and Drug Administration approved secukinumab (Cosentyx) for the treatment of ankylosing spondylitis in January 2016. The new data reported by Dr. Braun assessed the level of spinal pathology in a subgroup of the MEASURE 1 patients when measured by radiography using the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) at baseline and after 104 weeks on secukinumab treatment.

Patients in MEASURE 1 who began on active treatment received 10 mg/kg intravenous secukinumab for 4 weeks, followed by subcutaneous dosages of either 75 mg or 150 mg every 4 weeks for 104 weeks. His analysis also included some patients who entered MEASURE 1 in the placebo group and then switched to open-label, subcutaneous secukinumab treatment after 16 or 24 weeks on placebo.

Analysis of 168 patients who started on intravenous secukinumab and later received any subcutaneous secukinumab treatment out to 104 weeks showed an average increase in mSASSS of 0.30 after 104 weeks when compared against their baseline scores, reported Dr. Braun, professor and medical director of the Ruhr Rheumatology Center of the University of Bochum, Germany.

Among an additional 89 patients who began in the placebo group and then switched to subcutaneous secukinumab, the average change in mSASSS from baseline to 104 weeks was 0.54. By comparison, Dr. Braun noted that AS patients treated with a tumor necrosis factor inhibitor have shown 2-year progression in their mSASSS of about 0.8-0.9, and AS patients not treated with an active biologic drug have shown 2-year mSASSS progression of about 1.0.

A second analysis of the data reported by Dr. Braun showed that among the 168 patients treated for the full 104 weeks with secukinumab about 80% showed no mSASSS progression, but about 20% did have some level of detectable mSASSS progression.

The phase II study of tofacitinib (Xeljanz) randomized 208 patients with active AS to either tofacitinib at daily dosages of 2 mg bid, 5 mg bid, 10 mg bid, or placebo. The study’s primary endpoint was their ASAS20 response after 12 weeks that underwent a Bayesian Emax model analysis to estimate incremental efficacy when compared against placebo.

The primary efficacy analysis showed the greatest EmaxASAS20 response among patients treated with 5 mg bid daily, 63%, which was about 23% above the placebo level, reportedDr. Désirée van der Heijde, professor of rheumatology at the Leiden University Medical Center, The Netherlands. The absolute ASAS20 response rate of the 52 patients randomized to this tofacitinib dosage was about 81%, about 40% higher than the response rate seen in the 51 patients in the placebo arm.

All dosages of tofacitinib tested were well tolerated, with safety data similar to what has previously been shown for tofacitinib, a drug that has Food and Drug Administration approval for treating rheumatoid arthritis.

[email protected]

On Twitter @mitchelzoler

LONDON – Long-term treatment with the interleukin 17A inhibitor secukinumab showed suggestive evidence of inhibiting structural progression of spinal disease in 168 patients with ankylosing spondylitis, the first time any evidence for an effect like this has been seen with a biologic drug or any other agent used to treat ankylosing spondylitis.

However, the effect occurred in uncontrolled, 2-year open-label treatment of patients originally enrolled in one of the secukinumab pivotal trials, and the analysis did not include comparison against a historical control group, caveats that demand confirmation of this effect in additional studies, Dr. Jürgen Braun said at the European Congress of Rheumatology.

Mitchel L. Zoler/Frontline Medical News

In a second, unrelated study, the oral Janus kinase inhibitor tofacitinib showed promising efficacy for controlling clinical symptoms in patients with active ankylosing spondylitis (AS) during 12 weeks of treatment in a placebo-controlled, dose-ranging phase II study.

The open-label secukinumab extension study involved patients who had been enrolled in the MEASURE 1 study, one of the pivotal trials that had established secukinumab as safe and effective for improving the clinical status of patients with active AS. The primary endpoint of MEASURE 1 had been the percentage of patients achieving at least a 20% improvement in their Assessment of Spondyloarthritis international Society (ASAS20) response after 16 weeks of treatment (New Engl J Med. 2015 Dec 24;373[26]:2534-48).

Based in part on these data the Food and Drug Administration approved secukinumab (Cosentyx) for the treatment of ankylosing spondylitis in January 2016. The new data reported by Dr. Braun assessed the level of spinal pathology in a subgroup of the MEASURE 1 patients when measured by radiography using the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) at baseline and after 104 weeks on secukinumab treatment.

Patients in MEASURE 1 who began on active treatment received 10 mg/kg intravenous secukinumab for 4 weeks, followed by subcutaneous dosages of either 75 mg or 150 mg every 4 weeks for 104 weeks. His analysis also included some patients who entered MEASURE 1 in the placebo group and then switched to open-label, subcutaneous secukinumab treatment after 16 or 24 weeks on placebo.

Analysis of 168 patients who started on intravenous secukinumab and later received any subcutaneous secukinumab treatment out to 104 weeks showed an average increase in mSASSS of 0.30 after 104 weeks when compared against their baseline scores, reported Dr. Braun, professor and medical director of the Ruhr Rheumatology Center of the University of Bochum, Germany.

Among an additional 89 patients who began in the placebo group and then switched to subcutaneous secukinumab, the average change in mSASSS from baseline to 104 weeks was 0.54. By comparison, Dr. Braun noted that AS patients treated with a tumor necrosis factor inhibitor have shown 2-year progression in their mSASSS of about 0.8-0.9, and AS patients not treated with an active biologic drug have shown 2-year mSASSS progression of about 1.0.

A second analysis of the data reported by Dr. Braun showed that among the 168 patients treated for the full 104 weeks with secukinumab about 80% showed no mSASSS progression, but about 20% did have some level of detectable mSASSS progression.

The phase II study of tofacitinib (Xeljanz) randomized 208 patients with active AS to either tofacitinib at daily dosages of 2 mg bid, 5 mg bid, 10 mg bid, or placebo. The study’s primary endpoint was their ASAS20 response after 12 weeks that underwent a Bayesian Emax model analysis to estimate incremental efficacy when compared against placebo.

The primary efficacy analysis showed the greatest EmaxASAS20 response among patients treated with 5 mg bid daily, 63%, which was about 23% above the placebo level, reportedDr. Désirée van der Heijde, professor of rheumatology at the Leiden University Medical Center, The Netherlands. The absolute ASAS20 response rate of the 52 patients randomized to this tofacitinib dosage was about 81%, about 40% higher than the response rate seen in the 51 patients in the placebo arm.

All dosages of tofacitinib tested were well tolerated, with safety data similar to what has previously been shown for tofacitinib, a drug that has Food and Drug Administration approval for treating rheumatoid arthritis.

[email protected]

On Twitter @mitchelzoler

As many as one-third of healthy first-degree relatives of individuals with ankylosing spondylitis may meet the criteria for spondyloarthritis, according to results from a prospective cohort study.

Dr. Maureen C. Turina of the Amsterdam Rheumatology and Immunology Center at the University of Amsterdam and her coauthors enrolled 51 first-degree relatives of individuals with HLA-B27–positive ankylosing spondylitis in the study to see whether any of these otherwise healthy individuals showed early signs of the disease. They found that 17 (33%) of these first-degree relatives fulfilled any of the spondyloarthritis (SpA) classification criteria at baseline – a higher rate than reported in previous studies – and 7 (14%) met both the Assessment of Spondyloarthritis International Society (ASAS) criteria and European Spondyloarthropathy Study Group (ESSG) criteria.

©Rocky89/Thinkstock.com

The authors suggested that the higher rate, compared with previous studies, could be due to channeling bias, as individuals with clinical symptoms may have been more willing to participate in the study.

However, 4 of the 38 individuals who did not fulfill either of these criteria for SpA still showed imaging abnormalities – including syndesmophytes on the cervical spine and bone marrow edema in the sacroiliac joint.

The authors suggested these imaging abnormalities may represent a subclinical phase of SpA (Arthritis Rheumatol. 2016 May 23. doi: 10.1002/art.39766).

The participants who met the ASAS and/or ESSG classification criteria for SpA had more axial, entheseal, and joint pain, compared with those who did not meet the criteria. All of these patients also reported back pain, compared with 35% of those who did not fulfill the criteria.

However, the individuals meeting the SpA criteria had low overall disease scores, and did not show any increase in inflammatory serum markers.

“Importantly, some key features of SpA including the presence of peripheral disease or extra-articular manifestations and increased inflammatory parameters were only rarely observed in FDRs [first-degree relatives] and were also not different in those fulfilling the ASAS axSpA and/or ESSG classification criteria versus those who did not,” the authors reported.

“Future follow-up will learn if and which of these FDRs will evolve into the clinically established phase of SpA.”

When specifically asked, more than half (57%) of the first-degree relatives said they had back pain, and 40% said they had experienced or were experiencing arthralgia.

“The fact that these FDRs were not investigated for or diagnosed with axial SpA before inclusion in the study may be related either to the fact that the back pain symptoms were relatively mild or to ignorance of general physicians for these alarm symptoms,” the authors wrote.

One person said they had past or present peripheral arthritis but none reported enthesitis or dactylitis.

While none of the subjects had arthritis, 16% reported at least one tender joint, and 22% had a modified Schober score of less than 4.5 cm, with 4% showing a chest expansion of less than 3.6 cm.

Researchers also examined whether HLA-B27 status had any impact on the first-degree relatives, as previous studies had suggested that SpA is more likely to present in HLA-B27–positive first-degree relatives.

However they found no differences between the HLA-B27–positive and HLA-B27–negative groups in terms of demographics, symptom history, disease activity, clinical examination, or laboratory or imaging data; a finding the authors described as “intriguing.”

“However, if confirmed in a larger sample set, further follow-up of these FDRs will allow us to determine if FDRs showing signs and symptoms of SpA will evolve to more active and severe disease, independently of HLA-B27 status or, alternatively, if the presence of HLA-B27 may promote exacerbation and persistence of subclinical pathology.”

The study was supported by the Dutch Arthritis Foundation. No conflicts of interest were declared.

As many as one-third of healthy first-degree relatives of individuals with ankylosing spondylitis may meet the criteria for spondyloarthritis, according to results from a prospective cohort study.

Dr. Maureen C. Turina of the Amsterdam Rheumatology and Immunology Center at the University of Amsterdam and her coauthors enrolled 51 first-degree relatives of individuals with HLA-B27–positive ankylosing spondylitis in the study to see whether any of these otherwise healthy individuals showed early signs of the disease. They found that 17 (33%) of these first-degree relatives fulfilled any of the spondyloarthritis (SpA) classification criteria at baseline – a higher rate than reported in previous studies – and 7 (14%) met both the Assessment of Spondyloarthritis International Society (ASAS) criteria and European Spondyloarthropathy Study Group (ESSG) criteria.

©Rocky89/Thinkstock.com

The authors suggested that the higher rate, compared with previous studies, could be due to channeling bias, as individuals with clinical symptoms may have been more willing to participate in the study.

However, 4 of the 38 individuals who did not fulfill either of these criteria for SpA still showed imaging abnormalities – including syndesmophytes on the cervical spine and bone marrow edema in the sacroiliac joint.

The authors suggested these imaging abnormalities may represent a subclinical phase of SpA (Arthritis Rheumatol. 2016 May 23. doi: 10.1002/art.39766).

The participants who met the ASAS and/or ESSG classification criteria for SpA had more axial, entheseal, and joint pain, compared with those who did not meet the criteria. All of these patients also reported back pain, compared with 35% of those who did not fulfill the criteria.

However, the individuals meeting the SpA criteria had low overall disease scores, and did not show any increase in inflammatory serum markers.

“Importantly, some key features of SpA including the presence of peripheral disease or extra-articular manifestations and increased inflammatory parameters were only rarely observed in FDRs [first-degree relatives] and were also not different in those fulfilling the ASAS axSpA and/or ESSG classification criteria versus those who did not,” the authors reported.

“Future follow-up will learn if and which of these FDRs will evolve into the clinically established phase of SpA.”

When specifically asked, more than half (57%) of the first-degree relatives said they had back pain, and 40% said they had experienced or were experiencing arthralgia.

“The fact that these FDRs were not investigated for or diagnosed with axial SpA before inclusion in the study may be related either to the fact that the back pain symptoms were relatively mild or to ignorance of general physicians for these alarm symptoms,” the authors wrote.

One person said they had past or present peripheral arthritis but none reported enthesitis or dactylitis.

While none of the subjects had arthritis, 16% reported at least one tender joint, and 22% had a modified Schober score of less than 4.5 cm, with 4% showing a chest expansion of less than 3.6 cm.

Researchers also examined whether HLA-B27 status had any impact on the first-degree relatives, as previous studies had suggested that SpA is more likely to present in HLA-B27–positive first-degree relatives.

However they found no differences between the HLA-B27–positive and HLA-B27–negative groups in terms of demographics, symptom history, disease activity, clinical examination, or laboratory or imaging data; a finding the authors described as “intriguing.”

“However, if confirmed in a larger sample set, further follow-up of these FDRs will allow us to determine if FDRs showing signs and symptoms of SpA will evolve to more active and severe disease, independently of HLA-B27 status or, alternatively, if the presence of HLA-B27 may promote exacerbation and persistence of subclinical pathology.”

The study was supported by the Dutch Arthritis Foundation. No conflicts of interest were declared.

As many as one-third of healthy first-degree relatives of individuals with ankylosing spondylitis may meet the criteria for spondyloarthritis, according to results from a prospective cohort study.

Dr. Maureen C. Turina of the Amsterdam Rheumatology and Immunology Center at the University of Amsterdam and her coauthors enrolled 51 first-degree relatives of individuals with HLA-B27–positive ankylosing spondylitis in the study to see whether any of these otherwise healthy individuals showed early signs of the disease. They found that 17 (33%) of these first-degree relatives fulfilled any of the spondyloarthritis (SpA) classification criteria at baseline – a higher rate than reported in previous studies – and 7 (14%) met both the Assessment of Spondyloarthritis International Society (ASAS) criteria and European Spondyloarthropathy Study Group (ESSG) criteria.

©Rocky89/Thinkstock.com

The authors suggested that the higher rate, compared with previous studies, could be due to channeling bias, as individuals with clinical symptoms may have been more willing to participate in the study.

However, 4 of the 38 individuals who did not fulfill either of these criteria for SpA still showed imaging abnormalities – including syndesmophytes on the cervical spine and bone marrow edema in the sacroiliac joint.

The authors suggested these imaging abnormalities may represent a subclinical phase of SpA (Arthritis Rheumatol. 2016 May 23. doi: 10.1002/art.39766).

The participants who met the ASAS and/or ESSG classification criteria for SpA had more axial, entheseal, and joint pain, compared with those who did not meet the criteria. All of these patients also reported back pain, compared with 35% of those who did not fulfill the criteria.

However, the individuals meeting the SpA criteria had low overall disease scores, and did not show any increase in inflammatory serum markers.

“Importantly, some key features of SpA including the presence of peripheral disease or extra-articular manifestations and increased inflammatory parameters were only rarely observed in FDRs [first-degree relatives] and were also not different in those fulfilling the ASAS axSpA and/or ESSG classification criteria versus those who did not,” the authors reported.

“Future follow-up will learn if and which of these FDRs will evolve into the clinically established phase of SpA.”

When specifically asked, more than half (57%) of the first-degree relatives said they had back pain, and 40% said they had experienced or were experiencing arthralgia.

“The fact that these FDRs were not investigated for or diagnosed with axial SpA before inclusion in the study may be related either to the fact that the back pain symptoms were relatively mild or to ignorance of general physicians for these alarm symptoms,” the authors wrote.

One person said they had past or present peripheral arthritis but none reported enthesitis or dactylitis.

While none of the subjects had arthritis, 16% reported at least one tender joint, and 22% had a modified Schober score of less than 4.5 cm, with 4% showing a chest expansion of less than 3.6 cm.

Researchers also examined whether HLA-B27 status had any impact on the first-degree relatives, as previous studies had suggested that SpA is more likely to present in HLA-B27–positive first-degree relatives.

However they found no differences between the HLA-B27–positive and HLA-B27–negative groups in terms of demographics, symptom history, disease activity, clinical examination, or laboratory or imaging data; a finding the authors described as “intriguing.”

“However, if confirmed in a larger sample set, further follow-up of these FDRs will allow us to determine if FDRs showing signs and symptoms of SpA will evolve to more active and severe disease, independently of HLA-B27 status or, alternatively, if the presence of HLA-B27 may promote exacerbation and persistence of subclinical pathology.”

The study was supported by the Dutch Arthritis Foundation. No conflicts of interest were declared.