Long-Term Effects of Secukinumab on Fatigue in Ankylosing Spondylitis

Treatment with secukinumab in patients with ankylosing spondylitis (AS) was found to provide rapid and sustained improvements in fatigue for up to 3 years, regardless of prior tumor necrosis factor (TNF) inhibitor exposure, according to results of an analysis published in Arthritis Care & Research (Hoboken).

Study authors conducted an exploratory analysis of 2 phase 3 randomized, placebo-controlled trials — MEASURE 1 and MEASURE 2 (ClinicalTrials.gov Identifiers: NCT01358175 and NCT01649375, respectively) — to explore the long-term effects of secukinumab on fatigue in patients with active AS.

In both MEASURE 1 and MEASURE 2, patients with active AS were randomly assigned to receive secukinumab or placebo. In MEASURE 1, patients received either an intravenous 75-mg loading dose followed by a subcutaneous 150-mg maintenance dose or placebo. In MEASURE 2, patients received either a subcutaneous secukinumab 150-mg maintenance dose or placebo. Participants were either naive to or had an inadequate response/intolerance to TNF inhibitors. Fatigue was evaluated using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) scale.

Eligible patients were aged 18 years or more, had AS (as defined by the modified New York criteria), had an inadequate response or intolerance to nonsteroidal anti-inflammatory drugs, and had received either no prior treatment with anti-TNF therapy or experienced an inadequate response/intolerance to 1 or more anti-TNF agents.

At week 16, significant improvements in FACIT-F scores from baseline were observed with secukinumab vs placebo in both studies (P <.05). These improvements were sustained through week 156 and 104 in MEASURE 1 and MEASURE 2, respectively. Further, significantly more patients reported fatigue responses (FACIT-F increase of ≥4) with secukinumab 150 mg compared to placebo at week 16 in both MEASURE 1 (P <.05) and MEASURE 2 (P <.01).

Overall, 75.6% and 81.4% of participants achieved fatigue responses at week 156 and week 104 in the MEASURE 1 and MEASURE 2 trials, respectively. In addition, these findings were consistent in patients who were anti-TNF-naive and those who were anti-TNF-intolerant in MEASURE 1 (74.3% and 84.6%, respectively) and MEASURE 2 (81.3% and 75.0%, respectively).

Fatigue responses were moderately to strongly associated with responses in several clinical measures, including the Assessment of SpondyloArthritis International Society (ASAS)20/40, ASAS5/6 responses, AS Disease Activity Score-

C-reactive protein (ASDAS-CRP), Short-Form-36 scores, and Bath Ankylosing Spondylitis Disease Activity Index.

Study limitations included the lack of a control group after week 15, the exclusion of missing data, and potential selection bias towards patients who chose to continue to receive long-term secukinumab treatment.

Researchers concluded that the fatigue responses reported in the current analysis add to the existing evidence for secukinumab treatment in patients with AS.

Disclosure: The studies included in this analysis were supported by Novartis Pharma AG. Please see the original reference for a full list of authors’ disclosures.

Reference

Kvien TK, Conaghan PG, Gossec L, et al. Secukinumab provides sustained reduction in fatigue in patients with ankylosing spondylitis: long-term results of two phase III randomized controlled trials. Arthritis Care Res (Hoboken). Published online November 23, 2020. doi:10.1002/acr.24517