Is Treatment in Patients With Suspected Nonradiographic Axial Spondyloarthritis Effective? Six‐Month Results of a Placebo‐Controlled Trial

Abstract

Objective. To investigate the efficacy of 16-week treatment with etanercept (ETN) in patients with suspected nonradiographic axial spondyloarthritis (SpA).Methods. Tumor necrosis factor inhibitor-naive patients with inflammatory back pain with at least 2 SpA features and high disease activity (Bath Ankylosing Spondylitis Disease Activity Index score ≥4), without the requirement of a positive finding on magnetic resonance imaging (MRI) of the sacroiliac (SI) joint and/or elevated C-reactive protein (CRP) level, were randomized (1:1) to receive ETN (n = 40) or placebo (n = 40) for 16 weeks and subsequently were followed up for a further 8 weeks (to 24 weeks from baseline) without study medication. The primary end point was the Assessment of SpondyloArthritis international Society 20 (ASAS20) response at 16 weeks. Secondary end points included the Ankylosing Spondylitis Disease Activity Score (ASDAS) and changes in disease parameters, including the Bath Ankylosing Spondylitis Metrology Index (BASMI), CRP level, erythrocyte sedimentation rate (ESR), and Spondyloarthritis Research Consortium of Canada index scores (MRI of the SI joint), after 16 and 24 weeks.Results. Patient characteristics at baseline were comparable between the ETN and placebo groups. At 16 weeks, there was no significant difference in the percentage of patients exhibiting ASAS20 response between the ETN group (6 patients [16.7%]) and the placebo group (4 patients [11.1%]) (relative risk 0.7 [95% confidence interval 0.2-2.2], P = 0.5). Only the ESR showed more improvement in the ETN group compared to the placebo group at 16 weeks (decreases of 2.2 mm/hour and 1.4 mm/hour, respectively), but the difference did not reach statistical significance. Between 16 and 24 weeks, without study medication, the BASMI, CRP level, and ESR had worsened to a greater extent in the ETN group compared to the placebo group, with the difference being significant for the CRP level.Conclusion. This study shows that in patients with suspected nonradiographic axial SpA with high disease activity but without the requirement of a positive finding on SI joint MRI and/or elevated CRP level, treatment with ETN is not effective.

2022 French Society for Rheumatology (SFR) recommendations on the everyday management of patients with spondyloarthritis, including psoriatic arthritis

“…It is based on the same argument of lack of significant difference between TNF inhibitors (adalimumab, golimumab) and placebo during prospective controlled trials in non-radiographic axial SpA with normal CRP and no findings of inflammation on MRI [6]. This was confirmed in a recent study with etanercept in the same disease profile [97]. There is currently no data for IL17 antagonists or JAK inhibitors, thus no indication for starting these treatments in this situation.…”

Efficacy and safety of biological DMARDs: a systematic literature review informing the 2022 update of the ASAS-EULAR recommendations for the management of axial spondyloarthritis

“…One study of adalimumab in axSpA with a focus on imaging outcomes partially met its primary outcome (whole-body MRI smallest detectable change of ≥2.3 units met (44% vs 13%); SPARCC spine improvement of ≥5 units not met (36% vs 17%) after 6 weeks) and met several secondary outcomes (eg, ASAS40 48% for adalimumab vs 4% for placebo) 18. Finally, a trial of etanercept versus placebo in patients with ‘suspected axSpA’ (no objective signs of inflammation required) was negative 20. Only one small study at high risk of bias compared originator TNFi with an active control (online supplemental tables S3.11−S3.20).…”

Reply

“…The main point of concern of Mishra and colleagues is that patients with a suspected diagnosis of axial SpA on the basis of the presence of several risk factors, such as inflammatory back pain plus at least 2 SpA features as well as high patientreported disease activity (BASDAI ≥4) (1), as in our study, may not respond well to treatment with tumor necrosis factor inhibitors (TNFi) because objective signs of inflammation are lacking. As we have discussed in our article, we agree with the statement that the threshold for starting TNFi therapy, even in patients in whom a diagnosis of nonradiographic axial SpA is suspected but who have not been diagnosed as having nonradiographic axial SpA, is often too low.…”

“…To the Editor: I read with interest the reanalysis of the results of the SENSCIS trial by Dr. Maher et al (1). The extended findings in Maher and colleagues' study may represent an advance in the knowledge of the effects of nintedanib in systemic sclerosisassociated interstitial lung disease (SSc-ILD), but some aspects of the trial require additional commentary.…”