Interleukin 6 inhibition in refractory antisynthetase syndrome: case-based literature review

Abstract

ABSTRACT Introduction: Antisynthetase syndrome (ASyS) is a rare idiopathic inflammatory myopathy (IIM), characterised by the presence of anti-aminoacyl tRNA synthetase antibodies. Significant clinical heterogeneity often results in delayed or missed diagnoses. While corticosteroids are the primary treatment for ASyS, immunosuppressants are frequently added as steroid-sparing agents. In cases where conventional therapies have limited efficacy, the use of biological disease-modifying anti-rheumatic drugs (bDMARDs) is increasingly being explored. Given the suggested role of interleukin 6 (IL-6) in the onset and progression of ASyS, its inhibition could be a potential therapeutic option. Nevertheless, the clinical effects of IL-6 blockade remain to be awaited, given the unpredictability of its anti- and pro-inflammatory effects. Off-label use of IL-6 antagonists has shown favourable results in selected cases with ASyS. Material and methods: In this manuscript we present two patients with insufficient response to conventional treatment who received tocilizumab and sarilumab, two bDMARDs targeting IL-6. Results: Both patients had significant improvement in follow-up laboratory and pulmonary parameters as well as clinical symptoms with an additional corticoid-sparing effect. The treatment was well tolerated. Conclusion: Future randomised clinical trials in a selected ASyS patient population could elucidate the efficacy of IL-6 inhibition in this specific IIM subgroup.