MADRID – Secukinumab was superior to placebo for the primary endpoint of 20% improvement in Assessment of SpondyloArthritis international Society criteria (ASAS20), based on the initial 12-week data from the ongoing phase 3b MAXIMISE trial, the first randomized, controlled trial to evaluate a biologic therapy for the treatment of the axial manifestations of psoriatic arthritis (PsA).
“There was rapid and significant clinical improvement as measured with ASAS20 with both of the study doses of secukinumab,” an anti–interleukin-17 monoclonal antibody, reported, of Rheumazentrum Ruhrgebliet, Ruhr-University Bochum in Herne, Germany.
At the European Congress of Rheumatology, Dr. Baraliakos said that the 1-year data will be complete before the end of 2019.
In this primary analysis, 498 patients with established PsA were randomized to 150 mg secukinumab, 300 mg secukinumab, or placebo. For enrollment, all patients were required to have substantial axial pain and a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score greater than 4 despite treatment with at least two NSAIDs.
For the first 4 weeks of the trial, patients received their assigned therapies weekly by subcutaneous administration. Treatment thereafter was every 4 weeks.
Almost all patients had active psoriasis and axial symptoms of at least several years duration. The median patient age was 46 years. Approximately one-third were HLA B27 positive.
At baseline, the median back pain score on a visual analog scale of 100 was 73, and the median BASDAI score was greater than 7.0. More than 90% of patients reported back pain worsening with rest.
The proportion of patients achieving ASAS20 at 12 weeks was 63.1% in the group assigned to 300 mg secukinumab, 66.3% in those assigned 150 mg, and 31.1% for those assigned placebo (P less than .0001 for either active therapy versus placebo).
Analyses conducted with multiple imputations and comparing those who were and were not taking methotrexate produced almost the same relative advantage for secukinumab. ASAS20 responses in patients using concomitant methotrexate were 65.1% with 300 mg secukinumab, 67.3% with 150 mg secukinumab, and 33.9% with placebo. Corresponding values in the no-methotrexate group were 60.5%, 64.4%, and 27.1%, respectively.
“There was a good response from either dose of secukinumab no matter what analysis was employed,” reported Dr. Baraliakos, citing an odds ratio of 3.81 for reaching the primary endpoint with secukinumab versus placebo. There were no significant differences in efficacy between the doses of secukinumab.
There was “not much to say about safety,” according to Dr. Baraliakos, as no significant differences in any adverse events were observed between study arms. However, he did caution that longer-term exposure is needed for a more complete analysis of tolerability and safety.
Most patients with PsA are thought to eventually develop axial involvement, which has a major adverse affect on quality of life, according to Dr. Baraliakos. He considers this primary 12-week analysis encouraging, but said the 1-year data will provide more information about whether this therapy should be considered routinely in PsA patients with persistent axial symptoms.
Axial imaging was conducted at study entry even though it was not a criterion for enrollment. Dr. Baraliakos reported that the impact of secukinumab on objective imaging measures of disease activity, if any, is forthcoming.
Imaging data might be needed to establish benefit objectively, judging from a criticism of the study design that arose during discussion after the data were presented. Specifically, it was pointed out that improvement in ASAS20 and BASDAI could occur as a result of improvement in peripheral symptoms, such as enthesitis. The lack of axial-specific outcomes was called a potential weakness of this study.
Dr. Baraliakos countered that BASDAI evaluations did include axial-specific questions, but also confirmed that spine-specific outcomes are included among outcomes to be presented with longer-term analyses.
“These data will come,” said Dr. Baraliakos, referring to imaging as well as other outcomes that will provide more information on the impact of secukinumab in treating the axial involvement of PsA.
Dr. Baraliakos reported multiple financial relationships with pharmaceutical companies, including Novartis, which sponsored this trial.
SOURCE: Ann Rheum Dis. Jun 2019;78(Suppl2):195-6. Abstract . doi: 10.1136/annrheumdis-2019-eular.2932.