Inclusion myositis and sirolimus: the final results of the Rapami trial pave the way for a phase III

Sporadic inclusion myositis combines inflammatory processes and degeneration. It is the most common myositis after the age of 50, but also the only one that is refractory to the usual treatments for these autoimmune diseases (corticoids, immunosuppressants).

Between 2015 and 2017, with financial support from the AFM-Téléthon, Prof. Olivier Benveniste’s team conducted a randomised, double-blind, single-centre phase II/III clinical trial called Rapami. Its aim was to evaluate the efficacy, safety and tolerability of sirolimus or rapamycin (Rapamune®) at a dose of 2 mg/day versus placebo for one year in 44 participants aged between 45 and 80.

This compound, indicated for the prevention of rejection after renal transplantation, has a selective immunosuppressive action. It blocks the proliferation of effector T lymphocytes (while preserving regulatory T cells) and induces autophagy, processes which are impaired in inclusion myositis.

A stabilising trend

The final results of the Rapami trial show, after one year of treatment :

  • significant differences in the results of the 6-minute walk test, vital capacity, fat fraction in the thighs (MRI) and the HAQ-DI (Health Assessment Questionnaire without Disability Index) score, with a tendency towards stabilisation with sirolimus versus deterioration with placebo;
  • a visible and measurable effect on magnetic resonance imaging (MRI) and phosphorus 31 magnetic resonance spectroscopy of the lower limbs, making it possible to distinguish participants in the sirolimus group from those in the placebo group.
  • a decline in CD8+ and CD38+ effector T-cell subpopulations under sirolimus, correlated with the positive effects on the results of the 6-minute walk test;
  • similar results in the sirolimus and placebo groups for maximal voluntary isometric knee extension strength (primary endpoint of the trial) as well as for strength of the other muscle groups assessed (elbow flexion and extension, knee flexion, grip), dysphagia, IBMWCI and IBMFRS scores;
  • 45% of sirolimus-treated patients experienced serious adverse events, compared with 27% of placebo-treated patients;
  • treatment discontinuation for 18% of participants in the sirolimus group (n = 4) due to side effects (severe oral ulcerations, aseptic pneumonia, renal failure, oedema of the lower limbs).

To be confirmed in a multicentre study

For the investigators, the benefits of sirolimus in the 6-minute walk test could be explained by respiratory and metabolic effects rather than muscular effects. They were sufficient to justify the launch of the Optimism in IBM phase III trial, which is recruiting 140 participants in the United Kingdom, Australia, the Netherlands, the United States and Germany.


Sirolimus for treatment of patients with inclusion body myositis: a randomised, double-blind, placebo-controlled, proof-of-concept, phase 2b trial. Benveniste O, Hogrel JY, Belin L et al. The Lancet Rheumatology January 2021


Effect of sirolimus on muscle in inclusion body myositis observed with magnetic resonance imaging and spectroscopy. Reyngoudt H, Baudin PY, de Caldas de Almeida Araújo E et al. J Cachexia Sarcopenia Muscle. 2024 Apr 13.