User login
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.
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.
On Twitter @mitchelzoler
The results on radiographic progression in ankylosing spondylitis patients who continued on secukinumab treatment for 104 weeks suggest for the first time that a biologic drug can reduce radiographic progression of ankylosing spondylitis. This effect has not been seen in patients treated with a tumor necrosis factor inhibitor. The results showed that roughly 80% of the patients maintained for 2 years on secukinumab did not have radiographic progression, although the results also showed that about 20% of these patients did have detectable radiographic progression.
This analysis has several limitations and caveats. The study did not include a control group, not even a historical control group, and it involved open-label treatment. In addition, the treatment effect observed was very close to the level of a measurement error. It would help to compare these results with a historic control group, or to run a new study that compares the effect of secukinumab on long-term radiographic progression directly with the effect of treatment with a tumor necrosis factor inhibitor.
Because of these limitations the results of this analysis are of limited immediate value. Prior results have shown that clinically the efficacy of secukinumab for treating ankylosing spondylitis is more or less the same as the efficacy of various tumor necrosis factor inhibitors. If an additional effect from secukinumab on slowing radiographic progression in these patients were proven, it would be of clear added value, but further study is needed to show this.
The phase II study assessing the impact of tofacitinib, an oral Janus kinase inhibitor, on the clinical activity of ankylosing spondylitis shows promise for this drug in this setting. Currently, the only biologic drugs with proven activity in patients with ankylosing spondylitis are tumor necrosis factor inhibitors and the interleukin 17A inhibitor secukinumab. The data reported by Dr. van der Heijde show that tofacitinib is a good candidate to move to a phase III trial. In this phase II trial the activity seen with 5 mg bid of tofacitinib for reducing disease activity was more or less the same as has been seen with other active biologic drugs.
Dr. Denis Poddubnyy is a professor of rheumatology and head of rheumatology at the Benjamin Franklin campus of Charité Medical University in Berlin. He made these comments in an interview. He has been a consultant to Novartis and to Pfizer and to several other drug companies.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
The results on radiographic progression in ankylosing spondylitis patients who continued on secukinumab treatment for 104 weeks suggest for the first time that a biologic drug can reduce radiographic progression of ankylosing spondylitis. This effect has not been seen in patients treated with a tumor necrosis factor inhibitor. The results showed that roughly 80% of the patients maintained for 2 years on secukinumab did not have radiographic progression, although the results also showed that about 20% of these patients did have detectable radiographic progression.
This analysis has several limitations and caveats. The study did not include a control group, not even a historical control group, and it involved open-label treatment. In addition, the treatment effect observed was very close to the level of a measurement error. It would help to compare these results with a historic control group, or to run a new study that compares the effect of secukinumab on long-term radiographic progression directly with the effect of treatment with a tumor necrosis factor inhibitor.
Because of these limitations the results of this analysis are of limited immediate value. Prior results have shown that clinically the efficacy of secukinumab for treating ankylosing spondylitis is more or less the same as the efficacy of various tumor necrosis factor inhibitors. If an additional effect from secukinumab on slowing radiographic progression in these patients were proven, it would be of clear added value, but further study is needed to show this.
The phase II study assessing the impact of tofacitinib, an oral Janus kinase inhibitor, on the clinical activity of ankylosing spondylitis shows promise for this drug in this setting. Currently, the only biologic drugs with proven activity in patients with ankylosing spondylitis are tumor necrosis factor inhibitors and the interleukin 17A inhibitor secukinumab. The data reported by Dr. van der Heijde show that tofacitinib is a good candidate to move to a phase III trial. In this phase II trial the activity seen with 5 mg bid of tofacitinib for reducing disease activity was more or less the same as has been seen with other active biologic drugs.
Dr. Denis Poddubnyy is a professor of rheumatology and head of rheumatology at the Benjamin Franklin campus of Charité Medical University in Berlin. He made these comments in an interview. He has been a consultant to Novartis and to Pfizer and to several other drug companies.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
The results on radiographic progression in ankylosing spondylitis patients who continued on secukinumab treatment for 104 weeks suggest for the first time that a biologic drug can reduce radiographic progression of ankylosing spondylitis. This effect has not been seen in patients treated with a tumor necrosis factor inhibitor. The results showed that roughly 80% of the patients maintained for 2 years on secukinumab did not have radiographic progression, although the results also showed that about 20% of these patients did have detectable radiographic progression.
This analysis has several limitations and caveats. The study did not include a control group, not even a historical control group, and it involved open-label treatment. In addition, the treatment effect observed was very close to the level of a measurement error. It would help to compare these results with a historic control group, or to run a new study that compares the effect of secukinumab on long-term radiographic progression directly with the effect of treatment with a tumor necrosis factor inhibitor.
Because of these limitations the results of this analysis are of limited immediate value. Prior results have shown that clinically the efficacy of secukinumab for treating ankylosing spondylitis is more or less the same as the efficacy of various tumor necrosis factor inhibitors. If an additional effect from secukinumab on slowing radiographic progression in these patients were proven, it would be of clear added value, but further study is needed to show this.
The phase II study assessing the impact of tofacitinib, an oral Janus kinase inhibitor, on the clinical activity of ankylosing spondylitis shows promise for this drug in this setting. Currently, the only biologic drugs with proven activity in patients with ankylosing spondylitis are tumor necrosis factor inhibitors and the interleukin 17A inhibitor secukinumab. The data reported by Dr. van der Heijde show that tofacitinib is a good candidate to move to a phase III trial. In this phase II trial the activity seen with 5 mg bid of tofacitinib for reducing disease activity was more or less the same as has been seen with other active biologic drugs.
Dr. Denis Poddubnyy is a professor of rheumatology and head of rheumatology at the Benjamin Franklin campus of Charité Medical University in Berlin. He made these comments in an interview. He has been a consultant to Novartis and to Pfizer and to several other drug companies.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
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.
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.
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.
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.
On Twitter @mitchelzoler
AT THE EULAR 2016 CONGRESS
Key clinical point: Ankylosing spondylitis patients maintained on open-label secukinumab treatment for 2 years showed a low level of structural spinal progression in an uncontrolled study. Also, in a placebo-controlled phase II study, 12 weeks’ treatment of patients with active ankylosing spondylitis with 5 mg tofacitinib bid led to significant clinical responses, compared with placebo.
Major finding: Little to no radiographic progression occurred in about 80% of ankylosing spondylitis patients maintained on secukinumab for 104 weeks.
Data source: The secukinumab study involved an open-label, nonrandomized extension of treatment in 168 of the 371 patients originally enrolled in MEASURE 1. The tofacitinib study included 208 patients.
Disclosures: Patients in the secukinumab study had been enrolled in MEASURE 1, a study sponsored by Novartis, the company that markets secukinumab (Cosentyx). Dr. Braun has been a consultant to Novartis, and several other drug companies, and three of his coauthors are Novartis employees. The tofacitinib study was sponsored by Pfizer, the company that markets tofacitinib (Xeljanz). Dr. van der Heijde has been a consultant to Pfizer and several other drug companies, and five of her coauthors are Pfizer employees.
