Future of IIM TreatmentPreview
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Daratumumab

Daratumumab (anti-CD38) is being explored in IIM as a plasma-cell–depleting strategy, but at present the evidence base in myositis is not a traditional clinical-trial portfolio; it is dominated by case reports/letters and cross-disease summaries, with authors explicitly calling for prospective controlled trials. In the* largest systematic synthesis* of autoimmune (non-oncologic) use, 83 patients across 24 autoimmune diseases were reported (median 5 prior therapies; median 4daratumumab doses), with 81% described as remission/improvement; adverse events occurred in 45% (infusion reactions 20%, infections 19%, hypogammaglobulinemia 33%) and deaths in 3%—supporting biological plausibility but underscoring that rigorous disease-specific efficacy is unproven in IIM. [1]

The most “trial-like” IIM evidence remains preliminary, coming from dramatic single-patient rescue narratives in anti-MDA5 dermatomyositis with rapidly progressive ILD/ARDS, where daratumumab was layered onto intensive combination immunosuppression. In an ECMO-dependent anti-MDA5 ARDS case, daratumumab was given as four 1800 mg weekly subcutaneous injections, after ~3 weeks of nonresponse to multi-agent therapy; over ~2 months, imaging and oxygenation improved, MDA5 and Ro52 antibody levels turned negative, ECMO was removed 70 days after the first dose, prednisone was tapered from 50 mg/day to 10 mg/day, and ferritin decreased from 3100 µg/L to ~1600 µg/L(not normalized). [2]

Another published anti-MDA5 dermatomyositis RP-ILD report describes clinical remission with pulmonary improvement at 6 months, alongside depletion of CD38+ plasma cells and falling MDA5 antibody signal, again in a rescue context rather than as isolated drug effect. [3] A separate letter in anti-MDA5 RP-ILD likewise reports successful rescue use. [4]

“Established” IIM data now also include a cautionary counterexample: a case report of anti-synthetase syndrome in which daratumumab was stopped after five cycles for lack of durable benefit, with myositis recurring when prednisone was tapered to 30 mg/day, and the patient later dying of viral pneumonia (as reported). [5] This negative experience is important because it highlights likely effect modifiers (e.g., demonstrable plasma-cell biology, autoantibody phenotype, disease chronicity, and—critically—concurrent therapies) and reinforces the central limitation across the IIM literature: outcomes are confounded by combination immunosuppression and patient selection, making it difficult to attribute response or failure to daratumumab itself.

Together, the current IIM “signal” for daratumumab is best framed as phenotype-specific rescue experience (anti-MDA5; anti-SRP IMNM) rather than proven efficacy—pending prospective, controlled trials. [1,2,5,6]

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

  1. Holzer M-T, Ruffer N, Huber TB, et al. Daratumumab for autoimmune diseases: a systematic review. RMD Open. 2023;9(4):e003604.
https://pmc.ncbi.nlm.nih.gov/articles/PMC10729190/
  1. Ostendorf L, Muench F, Thormählen L, et al. Rescue combination treatment of anti-MDA5-associated ARDS with daratumumab. RMD Open. 2023;9(3):e003238.
https://pmc.ncbi.nlm.nih.gov/articles/PMC10364176/
  1. Holzer MT, Nies JF, Oqueka T, et al. Successful rescue therapy with daratumumab in rapidly progressive interstitial lung disease caused by MDA5-positive dermatomyositis. Chest. 2023;163(1):e1–e5.
https://pubmed.ncbi.nlm.nih.gov/36628678/
  1. Chua C-G, Chai G-T, Lim XR, et al. Successful rescue treatment of refractory anti-MDA5 autoantibody positive dermatomyositis with rapidly progressive interstitial lung disease using daratumumab. Clin Exp Rheumatol. 2024;42:460–461.
https://www.clinexprheumatol.org/abstract.asp?a=20641
  1. Nguyen N, Hudson M, et al. Failure of daratumumab in the treatment of anti-synthetase syndrome: a case report.SAGE Open Med Case Rep. 2025.
https://pmc.ncbi.nlm.nih.gov/articles/PMC12041689/
  1. Landon-Cardinal O, Allard-Chamard H, Chapdelaine H, et al. Daratumumab as a rescue therapy in severe refractory anti-SRP immune-mediated necrotising myopathy. Ann Rheum Dis. 2023;82(4):579–580.
https://pubmed.ncbi.nlm.nih.gov/36609342/