AT RHEUMATOLOGY 2016
GLASGOW, SCOTLAND (FRONTLINE MEDICAL NEWS) – Treatment with the anti–interleukin-17A monoclonal antibody secukinumab improved a range of patient-reported outcome measures in a phase III trial of patients with ankylosing spondylitis.
Physical function, quality of life, fatigue, and work productivity were all significantly improved from baseline after 16 weeks of treatment with secukinumab (Cosentyx) versus placebo, and the effects were sustained for up to 1 year.
“PROMs [patient-reported outcome measures] are increasingly seen as the most important outcome measures [in trials] because of their importance to patients,” and they are very closely related to long-term retention and patients’ overall quality of life, Dr. Paul Emery said at the British Society for Rheumatology annual conference.
The new findings come from the MEASURE 2 study, a randomized, double-blind trial of 219 patients treated with one of two doses of secukinumab (150 mg or 75 mg) or placebo. Around 60% of the patient population was male, 95% were white, with a mean age around 42-44 years.
The primary endpoint data from the trial, which was the proportion of patients with at least as 20% improvement in Assessment of Spondyloarthritis International Society (ASAS 20) response criteria at 16 weeks, were published recently ( N Engl J Med. 2015;373:2534-48 ) with the results of the MEASURE 1 study. These showed that a significantly higher percentage of patients treated with the recommended dose of 150 mg, given as a subcutaneous injection every week for the first 3 weeks, then every 4 weeks from week 4, achieved ASAS 20 versus placebo (61% vs. 28%, P less than .001). Effects were sustained, with 62.5%-73.8% of patients still at ASAS 20 at 1 year depending on the type of data analysis performed, and 75% of those who switched from placebo at 16 weeks. The highest response rates were seen in patients who had not received prior anti-TNF therapy (82% vs. 60% for prior therapy at 1 year).
Changes in patients’ general and disease-specific quality of life from baseline to week 16 were predefined secondary endpoints assessed in the MEASURE 2 trial and were determined by the Short-Form (SF) 36 Physical Component Score (PCS) and the AS Quality of Life (ASQoL) questionnaire. Other exploratory endpoints included assessment of these measures at 1 year and the effect of treatment on the SF-36 Mental Component Score (MCS), Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue questionnaire, and the Work Productivity and Activity Impairment-General Health (WPAI-GH) questionnaire.
“One of the things about secukinumab is that you do get very fast responses in the things that matter,” said Dr. Emery of the Leeds (England) Institute of Rheumatic and Musculoskeletal Medicine at the University of Leeds.
Improvement in SF-36 PCS showed improvement as early as week 4, with a mean increase of 6 points from baseline with secukinumab 150 mg versus only 1.9 points for placebo at week 16, and a sustained improvement of 8 points by 1 year. The minimal clinically important difference (MCID) for change in SF-36 is 2.5 points or more. There was not such a clear-cut difference for the SF-36 MCS, but there was a clinically significant improvement of about 4 points at 16 weeks and 6.5 by 1 year.
There was a significant improvement in quality of life versus placebo measured using the ASQoL instrument, with a mean reduction of 4 points for the recommended dose of secukinumab at 16 weeks versus a 1.4 reduction for placebo, and a 5.23 reduction for secukinumab at 1 year. Here the MCID is a change of 1.8 points, Dr. Emery reported.
The MCID for changes in the FACIT-Fatigue score is 4 points or more and this was passed by secukinumab 150 mg at both 16 weeks, with a change of 8 points versus 3.3 points for placebo, and at 1 year, with an increase of 11.5 points for secukinumab.
Work productivity impairment was also improved with active treatment, with mean changes in the WPAI-GH from baseline to week 16 of –16.36 versus –10.22 for placebo, and a sustained reduction of 21.33 at 1 year. Higher scores on this outcome measure mean that work productivity is more severely affected.
Secukinumab was approved for use in ankylosing spondylitis by the European Medicines Agency in October 2015 and more recently by the Food and Drug Administration in January this year. Its availability could be a potential “game changer” for these patients, Dr. Emery suggested, because its mode of action is different from other available therapies, notably the tumor necrosis factor inhibitors. It could become the treatment of choice for AS patients, partially those with enthesitis and psoriasis, at least before drugs that target interleukin (IL)-23 become available that may be better for addressing the spinal component of the disease, he noted during the Q&A that followed his presentation.
Data on radiographic progression will be presented separately, Dr. Emery noted during discussion. He added that secukinumab “certainly works” to reduce radiographic progression, but whether or not it is better than anti-TNF therapy remains to be seen. Because of the mechanism of action on IL-17A, secukinumab could potentially offer an advantage, he said.
“I think it is a game changer because we’ve had such restricted access to therapy previously,” Dr. Emery said. Now having drugs with two different modes of action is a bonus. Deciding which to use first, and in which patients, is the next issue to address.
Novartis supported the study. Dr. Emery has been a paid consultant to AbbVie, Bristol-Myers Squibb, Merck, Novartis, Pfizer, Roche, UCB, Lilly, Samsung, and Sandoz.