JAK1 inhibition shows remarkable efficacy in AS

More than half of patients with active ankylosing spondylitis (AS) gained an ASAS40 response at week 14 with the selective Janus kinase (JAK)1 inhibitor upadacitinib [1].

There is a high medical need for patients with AS who have an inadequate response/contraindication to non-steroidal anti-inflammatory drugs (NSAIDs). Although TNF inhibitors are approved in AS and have demonstrated efficacy across key disease domains, a significant proportion of patients still have inadequate or poor response or may not tolerate these therapies. Therefore, novel treatment options are urgently needed. AS involves a range of immune cell types and cytokines, many of which utilise JAK pathways for signalling.

This was the rationale to assess the efficacy and safety of the selective JAK1 inhibitor upadacitinib in patients with AS that showed an inadequate response to NSAIDs. In the double-blind, placebo-controlled, phase 2/3 study SELECT-AXIS 1, patients with AS were treated with 15 mg upadacitinib or placebo. All included patients (n=187) met modified New York Criteria for AS based on central reading of radiographs, had a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) ≥4 and a total back pain ≥4 in a numeric rating scale from 0–10. They were biologic-naïve and had an inadequate response to ≥2 NSAIDs or intolerance/contraindication for NSAIDs. The primary study endpoint was an ASAS40 response at week 14.

“Twice as many patients in the upadacitinib group met the primary endpoint compared to placebo”, said Prof. Désirée van der Heijde (Leiden University Medical Center, the Netherlands) during the presentation of the study (51.6% vs 25.5%; P=0.0003; see Figure). In addition, there was also a significant superiority in a couple of secondary endpoints, e.g. the BASDAI50 at week 14, the difference in the Ankylosing Spondylitis Disease Activity Scores, and the ASAS partial response.

Upadacitinib showed also good tolerability with similar numbers of serious adverse events, infections, and adverse events that led to treatment discontinuation in the placebo and the upadacitinib group. No serious infections, herpes zoster, malignancy, venous thromboembolic events, or deaths were reported. “There was also a rapid effect already after only 2 weeks”, said Prof. van der Heijde. Therefore, the JAK inhibitor could be a valuable addition to the present treatment armamentarium.

Figure. Significantly more patients treated with upadacitinib achieved the primary endpoint of ASAS40 response at week 14 [1]

ASAS, Assessment of SpondyloArthritis International Society; CI, confidence interval

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   1. van der Heijde D et al. Abstract 2728. ACR 2019. November 8-13, Atlanta (GA/USA).

Posted on 4 February 202017 May 2024