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

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.

In this manuscript we present two patients with insufficient response to conventional treatment who received tocilizumab and sarilumab, two bDMARDs targeting IL-6.

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.

Future randomised clinical trials in a selected ASyS patient population could elucidate the efficacy of IL-6 inhibition in this specific IIM subgroup.