Treatment with secukinumab (Cosentyx) led to sustained remission or low disease activity using a novel, stringent outcome measure in patients with psoriatic arthritis (PsA), a post-hoc analysis of a phase III trial found.
On the Psoriatic Arthritis Disease Activity Score (PASDAS), which evaluates multiple aspects of PsA, remission and low disease activity at 16 weeks were achieved by 15.6% and 22.9% of patients receiving 300 mg subcutaneous secukinumab every 4 weeks and by 15.2% and 19.2% of those given 150 mg every 4 weeks, and those numbers persisted throughout 2 years of follow-up, according to Laura C. Coates, MBChB, PhD, of the University of Oxford in England, and colleagues.
For patients randomized to placebo, in contrast, rates of remission and low disease activity were achieved by only 2.3% and 13.8% at week 16, the researchers reported online in .
The PASDAS is a composite score that includes patient and physician global scores of skin and joint disease, swollen and tender joint counts, Leeds enthesitis index, tender dactylitis count, the physical component of the Short Form (SF) 36 Health Survey, and level of C-reactive protein. It was developed by the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis and the European League Against Rheumatism. Most other outcome measures such as the criteria of the American College of Rheumatology (ACR) focus exclusively on the joints, ignoring the multifaceted aspects of PsA.
On the PASDAS, remission was defined as a score of 1.9 or less, low disease activity was a score from 1.9 to 3.2, moderate activity was a score from 3.2 to 5.4, and high activity was a score of 5.4 or higher.
Secukinumab is a monoclonal antibody that targets interleukin 17A. The study, known as FUTURE 2, included 298 patients who had active PsA, with mean baseline PASDAS scores of 5.9, 6, and 5.8 in the 300 mg, 150 mg, and placebo groups, respectively. After week 16, all patients received the active treatment.
Participants' mean age was 48, disease duration was 7 years, and about two-thirds had not previously received a tumor necrosis factor (TNF) inhibitor.
In , a 20% response on the ACR criteria was seen at week 24 by 54% of patients receiving the 300 mg dose and by 51% of those given 150 mg compared with 15% of those receiving placebo (P<0.0001 for both doses).
At week 104, remission according to the multicomponent PASDAS had been achieved by 22.9% and 14.3% of the 300 mg and 150 mg groups, while low disease activity had been achieved by 36.1% and 35.1%, respectively.
Among patients who were in remission at week 16, 60% were still in remission and 40% had low disease activity at week 104. For those who had low disease activity at week 16, 79% had either maintained that response or improved by week 104.
More patients who were anti-TNF naive were considered to be in remission or to have low disease activity at week 16: 46.2% of the 300 mg group and 42.9% of the 150 mg group compared with 22.6% and 19.4% of those who were anti-TNF experienced. Responses at week 16 were maintained throughout the 2 years for both anti-TNF naive and experienced.
The PASDAS components that showed the most improvement were dactylitis, enthesitis, and the SF-36 physical component.
Coates and colleagues also looked at the effects of secukinumab treatment on patient-reported outcomes including disability, quality of life, and fatigue, and found that scores for these outcomes were higher throughout the 2 years for patients who were in remission or had low disease activity. Those patients also had significantly less activity and work impairment than those with high disease activity.
These improvements in patient-reported outcomes that persisted through week 104 confirmed "that these stringent goals translate into improved patient quality of life and function as well as for society owing to higher workforce productivity," the researchers noted.
They concluded that the PASDAS may be a suitable endpoint for future clinical trials in PsA, more accurately reflecting the disease state than measures like the ACR20, although it requires mathematical calculations that can be time consuming. It also does not account for patient pain and axial manifestations.
Disclosures
The study was sponsored by Novartis.
The authors reported support and funding from the National Institute for Health Research and multiple companies including AbbVie, Janssen, Eli Lilly, Novartis, Pfizer, Amgen, Bristol-Myers Squibb, Celgene, Pfizer, UCB, Merck, Boehringer Ingelheim Sun Parma, Prothena, Galapagos, Roche, Celltrion, Epirus, Mundipharma, Oktal, Orion, Genentech, and Sanofi. Several are employees and shareholders in Novartis.
Primary Source
Arthritis Research & Therapy
Coates L, et al "Secukinumab provides sustained PASDAS-defined remission in psoriatic arthritis and improves health-related quality of life in patients achieving remission: 2-year results from the phase III FUTURE 2 study" Arthritis Res Ther 2018; doi:10.1186/s13075-018-1773-y.