Secukinumab shows sustained efficacy and low structural progression in ankylosing spondylitis: 4-year results from the MEASURE 1 study

Abstract

Objective To evaluate the effect of secukinumab, a fully human anti-interleukin-17A monoclonal antibody, on efficacy, imaging outcomes, and safety through 4 years (208 weeks) in patients with ankylosing spondylitis. Methods Patients opting to enrol had completed 2 years’ treatment in the MEASURE 1 core study with subcutaneous secukinumab 150 or 75 mg every 4 weeks (q4Wk), following intravenous loading to Week (Wk) 4, or placebo treatment to Wk16/24. Up-titration from secukinumab 75–150 mg q4Wk was permitted following a protocol amendment. Efficacy is reported for patients originally randomized to secukinumab. Radiographic changes were assessed using the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) and changes in MRI measures of inflammation using the Berlin scoring method. Safety and tolerability were evaluated. Results Among 274 extension study participants, 89.7% (78/87) and 93.0% (93/100) originally randomized to secukinumab 150 and 75 mg, respectively, completed 208Wk. Through Wk208, Assessment of Spondyloarthritis International Society 20/40 (observed) were 79.7%/60.8% (150 mg), 71.0%/43.5% (75 mg) and 80.0%/76% (up-titrators; n = 25). Mean (s.d.) changes in mSASSS were 1.2 (3.91) (150 mg), 1.8 (4.32) (75 mg) and 1.6 (5.67) (up-titrators). No radiographic progression (mSASSS change from Baseline < 2) was observed in 79% of patients receiving either secukinumab dose. Exposure-adjusted incidence rates per 100 patient-years were: serious infections (1.0), Candida infections (0.4), Crohn’s disease (0.6), ulcerative colitis (0.2), and malignant/unspecified tumours (0.5), with no new safety signals. Conclusion Through 4 years, secukinumab provided sustained efficacy on signs and symptoms, and MRI outcomes, a low rate of radiographic progression and a consistent safety profile. Trial registration NCT01863732.

The Brazilian Society of Rheumatology guidelines for axial spondyloarthritis – 2019

“…seventy-one of the patients in the 150 mg group (73,2%) had at least baseline and week 208 radiographs. The rates of progression in the 0-2, 2-4, and 0-4 years intervals were, respectively, 0.5 ± 1.69; 0.7 ± 3.32; and 1.2 ± 3.91, respectively [177]…”

Nonsteroidal Antiinflammatory Drugs as Potential Disease‐Modifying Medications in Axial Spondyloarthritis

“…However, this approach has not shown associations between the dose of biologics and progression. In a 4‐year secukinumab study , although the 150 mg group had marginally less radiographic progression than the 75 mg groups as measured by mSASSS, the 75 mg groups had higher mSASSS at baseline, which is a risk factor for radiographic progression. In addition, similar proportions of patients in each dosing group (78.9% versus 78.6%) had no radiographic progression (mSASSS change ≤2).…”

“…The second strategy, similar to that used in the NSAIDs trials, was to compare different dosing regimens with the question of whether there was a dose effect (Table ). However, this approach has not shown associations between the dose of biologics and progression.…”

Varicella Zoster and Cutaneous Candida Infection in a Patient With Ankylosing Spondylitis Under Treatment With Secukinumab

“…Candida infections were observed in 68 of the 3,133 patients. [6][7][8][9][10][11][12] Most of these were oral, vulvovaginal and esophageal candidiasis. Cutaneous candidiasis was reported only in one patient.…”