Nocebo effects of Janus kinase inhibitors in the treatment of active ankylosing spondylitis

Abstract

Ankylosing spondylitis (AS) is a chronic inflammatory condition associated with enthesis and inflammation of the spinal and sacroiliac joints, and it ultimately contributes to the erosion of bone and joints [1, 2, 3]. There is an unmet need to elucidate alternative modes of action to efficiently control AS, and this has led to the recent introduction of Janus kinase (JAK) inhibitors [4, 5, 6]. The nocebo effect, the negative equivalent of the placebo effect, refers to the adverse events (AEs) that arise after administration of an inactive drug with no active therapeutic advantage [7]. The nocebo effect is a factor relevant to the development of medications and the design of randomized controlled trials (RCTs) [8]. Significant nocebo effects can result in incorrect evaluation of treatment-related AEs because they increase the proportion of AEs in the placebo group or unrelated AEs in the patient group receiving active therapy [7]. These problems are particularly important because the nocebo effect is influenced by accumulated experience pertaining to a disease and is thought to be most marked in chronic diseases like AS where patients need multiple disease-management therapies [9]. We have examined possible discrepancies in the proportion of AEs between patients randomized to receive placebo and those randomized to receive the active comparator in randomized, placebo-controlled clinical trials involving JAK inhibitors for the treatment of AS [10, 11, 12].