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Tacrolimus

Tacrolimus (a calcineurin inhibitor) has the most “trial-like” evidence in IIM in PM/DM-associated interstitial lung disease (ILD), with smaller prospective data for refractory muscle disease. Early prospective, open, non-randomized work in refractory dermatomyositis/polymyositis (n=9) reported clinical improvement at 6 months in 8/9 patients (all 5 DM and 3/4 PM), with better responses suggested when tacrolimus trough >5 ng/mL and disease duration <4 years; reported toxicities were limited mainly to moderate hypertension and worsening diabetes in this small cohort. [1]

Prospective ILD data come from the IMPPACT multicenter, *single-arm, *52-week clinical trial testing initial combination therapy (tacrolimus plus glucocorticoids) for active PM/DM-interstitial pneumonia. Tacrolimus was dosed at 0.075 mg/kg/day and adjusted to a target whole-blood trough 5–10 ng/mL, with prednisolone 0.6–1.0 mg/kg/day followed by taper. Among 26 treated patients, the 52-week survival was 88.0% (95% CI 67.3–96.0). Serious adverse events occurred in 44.0% (11/25–26, as reported), including four opportunistic infections, illustrating both the potential benefit signal (survival) and the real infection burden in this high-risk phenotype under intensive immunosuppression. [2]

The most rigorous comparative evidence is a prospective multicenter randomized, open-label phase 2 trial in PM/DM-ILD comparing prednisolone + tacrolimus vs prednisolone + cyclosporine A over 52 weeks (n=58; tacrolimus n=30, cyclosporine n=28). The primary endpoint, progression-free survival (PFS) at 52 weeks, was 87% with tacrolimus vs 71% with cyclosporine (P=0.16), while overall survival at 52 weeks was 97% vs 93% (P=0.50). %FVC increased in both arms (per-protocol), and no patients discontinued due to adverse events.

Taken together, tacrolimus has a consistent prospective signal in PM/DM-ILD (single-arm survival and randomized PFS trend), but definitive superiority over other calcineurin-based regimens and long-term outcomes remain incompletely proven. [3]

References (numbered to match text; each includes a link)

  1. Matsubara S, Kondo K, Sugaya K, Miyamoto K. Effects of tacrolimus on dermatomyositis and polymyositis: a prospective, open, non-randomized study of nine patients and a review of the literature. Clin Rheumatol.2012;31(10):1493-1498. doi:10.1007/s10067-012-2044-y.

https://pubmed.ncbi.nlm.nih.gov/22886003/
  1. Takada K, Katada Y, Ito S, et al. Impact of adding tacrolimus to initial treatment of interstitial pneumonitis in polymyositis/dermatomyositis: a single-arm clinical trial. Rheumatology (Oxford). 2020;59(5):1084-1093.

https://pmc.ncbi.nlm.nih.gov/articles/PMC7850120/
  1. Fujisawa T, Hozumi H, Kamiya Y, et al. Prednisolone and tacrolimus versus prednisolone and cyclosporin A to treat polymyositis/dermatomyositis-associated ILD: a randomized, open-label trial. Respirology. 2021;26(4):370-377. doi:10.1111/resp.13978.

https://pubmed.ncbi.nlm.nih.gov/33179395/