Background and Importance Nine drugs are currently approved for the treatment of ankylosing spondylitis (AS) in adults: adalimumab, certolizumab pegol, etanercept, golimumab, infliximab, ixekizumab, secukinumab, upadacitinib and tofacitinib. Tofacitinib was the last of them to receive its approval. However, there are no direct comparisons between them.
Aim and Objectives To establish whether the drugs approved for AS in adults can be considered equivalent therapeutic alternatives (ATE) in efficacy in AS.
Material and Methods A search of clinical trials of these drugs in adult patients with AS was conducted, phase II or III, double-blinded, controlled with another drug or placebo.
Other inclusion criteria were
Endpoint: ASAS40 (a ≥40% improvement and an absolute improvement from baseline of the Assessment in SpondyloArthritis International Society).
Follow-up time: 12-16 weeks.
Other inclusion criteria wereFor those drugs with more than one study, a previous meta-analysis was performed using Joaquin Primo calculator. An adjusted indirect comparison (IC) of the drugs used in AS versus tofacitinib was performed using the Bucher method, using Joaquin Primo calculator. Due to lack of data in the literature and considering that therapy failure can be recovered with second lines, half of the ASAS40 value obtained in meta-analysis was taken as delta value. ATE guide was followed in order to establish a positioning.
Sixteen studies were included 4 adalimumab, 2 golimumab, 1 infliximab, 1 certolizumab, 2 etanercept, 1 upadacitinib, 2 tofacitinib, 1 secukinumab and 2 ixekizumab. The difference in ASAS40 of the drugs before versus tofacitinib expressed as RAR (IC 95%) was: Adalimumab [4 (-6,1; 14,1)], certolizumab [-7,3 (-25,1; 10,5)], etanercept [2 (-11,5; 15,5)], golimumab [-5 (-16,3; 6,3)], infliximab [8,43 (-4,8; 21,6)], ixekizumab [-9 (-20, 6; 2,6)], secukinumab [-2,7 (-18,3; 12,9)], upadacitinib [-1,9 (-17,8; 13,9)]. Adalimumab, etanercept and tofacitinib are considered ATE. Infliximab, upadacitinib, secukinumab, golimumab, certolizumab, ixekizumab and tofacitinib can also be considered ATE, being the probability of clinically relevant difference <50% (most of the 95% CI is in the equivalence range) and the failure does not involve serious/irreversible damage.
Conclusion and Relevance Tofacitinib and the rest of these drugs could be considered ATE. For a definitive statement, the criteria of safety and adequacy should be considered.
Conflict of Interest No conflict of interest
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