Clinical and Economic Benefit of Advanced Therapies for the Treatment of Active Ankylosing Spondylitis

Abstract

Introduction: Recent changes to treatment guidelines for ankylosing spondylitis (AS) have listed first-line advanced therapies as tumor necrosis factor (TNF), interleukin (IL)-17, and Janus kinase (JAK) inhibitors. This study sought to assess the comparative clinical and economic benefit of advanced therapies approved for AS.

Methods: A systematic literature review was conducted to identify randomized clinical trials for JAK inhibitors (upadacitinib [UPA], tofacitinib [TOF]), anti-IL-17 therapies (secukinumab [SEC], ixekizumab [IXE]), and TNF inhibitors (adalimumab [ADA], etanercept [ETN], golimumab [GOL]) used for the treatment of active AS. Clinical efficacy was evaluated by Assessment of Spondyloarthritis International Society 40 (ASAS40) criteria and treatment discontinuation due to adverse events (AEs) was used to generate response rates synthesized via a Bayesian network meta-analysis. Number needed to treat (NNT) was calculated as the reciprocal of incremental response rate of each treatment versus placebo. Cost per ASAS40 responder (CPR) was calculated as the 12-week treatment costs divided by ASAS40 response rates. Data were stratified by biologic treatment status (i.e., biologic naïve [bio-naïve] or inadequate response or intolerance to biologics [bio-IR]) for efficacy and CPR analyses.

Results: Among bio-naïve patients, the response rate for ASAS40 was 53.6% for UPA-treated patients, whereas most other treatments had response rates between 41% and 49%. NNTs were lowest for UPA-treated patients at 2.8 (other therapies 3.2-4.8). Estimated CPR among UPA-treated patients was lowest (UPA $39.5k vs others $44.2k-102.5k). Efficacy and CPR trends were similar among bio-IR and TNF-IR patients. Among bio-naïve and bio-IR patients, the rate of AEs leading to discontinuation was lowest among UPA and SEC-treated patients (0.0, others 0.6-3.7%).

Conclusions: Relative to other treatments assessed in this study, UPA demonstrated numerically greater clinical and economic benefit for the treatment of AS. Head-to-head or real-world comparisons of these therapies are warranted and may inform clinical decision-making.

Keywords: Ankylosing spondylitis; Network meta-analysis; Treatment effectiveness; Upadacitinib.

Fig. 1

Absolute ASAS40 response rates at week 12–16 in bio-naïve (a) and bio-IR (b) patients with AS. ^aIXE 80 mg was administered every 4 weeks. ^bPatients received SEC 150 mg without a loading dose. ADA adalimumab, ARR absolute rate ratio, ASAS40 Assessment of Spondyloarthritis International Society improvement ≥ 40%, Bio biologic disease-modifying antirheumatic drug, CrI credible interval, ETN etanercept, GOL golimumab, IR inadequate response or intolerance, IXE ixekizumab, JAK Janus kinase, PBO placebo, SEC secukinumab, TOF tofacitinib, UPA upadacitinib

Fig. 2

Cross-tabulation of estimated absolute rates of discontinuation due to AEs versus rates of ASAS40 among bio-naïve (a) and bio-IR (b) patients with AS. ADA40 adalimumab 40 mg, AE adverse event, ASAS40 Assessment of Spondyloarthritis International Society improvement ≥ 40%, Bio biologic disease-modifying antirheumatic drug, ETN25/30 etanercept 25 mg/50 mg, GOL50 golimumab 50 mg, GOL100 golimumab 100 mg, IL interleukin, IR inadequate response or intolerance, IXE80Q4W ixekizumab 80 mg every 4 weeks, JAK Janus kinase, LD loading dose, PBO placebo, SEC150 secukinumab 150 mg, SEC300 secukinumab 300 mg, TNF tumor necrosis factor, TOF5 tofacitinib 5, UPA15 upadacitinib 15 mg. Rates for any treatment discontinuation due to AEs were assessed at weeks 12–24 and rates for ASAS40 were assessed at weeks 12–16

Fig. 3

Number needed to treat for ASAS40 at week 12–16 in bio-naïve (a) and bio-IR (b) patients with AS. ^aIXE 80 mg was administered every 4 weeks. ^bPatients received SEC 150 mg without a loading dose. ADA adalimumab, ARR absolute rate ratio, ASAS40 Assessment of Spondyloarthritis International Society improvement ≥ 40%, Bio biologic disease-modifying antirheumatic drug, CrI credible interval, ETN etanercept, GOL golimumab, IR inadequate response or intolerance, IXE ixekizumab, JAK Janus kinase, NNT number needed to treat, PBO placebo, SEC secukinumab, TOF tofacitinib, UPA upadacitinib

Fig. 4

Cost per responder for ASAS40 over 16 weeks in bio-naïve (a) and bio-IR (b) patients with AS. ^aIXE 80 mg was administered every 4 weeks. ^bPatients received SEC 150 mg without a loading dose. ADA40 adalimumab, ARR absolute rate ratio, ASAS40 Assessment of Spondyloarthritis International Society improvement ≥ 40%, Bio biologic disease-modifying antirheumatic drug, CPR cost per responder, CrI credible interval, ETN etanercept, GOL golimumab, IR inadequate response or intolerance, IXE ixekizumab, JAK Janus kinase, PBO placebo, SEC secukinumab, TOF tofacitinib, UPA upadacitinib