‘Strong’ treatment predictions in inflammatory myositis Save

For many years, the treatment algorithm in inflammatory myositis was:

Glucocorticoids
Immune suppression (MTX, MMF, tacrolimus)
And in more severe cases or recalcitrant to treatment: IVIg, Rituximab, rarely cyclophosphamide

Then: 
Tofacitinib was used for calcinosis and JAKi acquired positive observational data in ILD
Triple therapy became popular in severe IM: high dose steroids, CNI (TAC or cyclosporine) and Rituximab or intravenous cyclophosphamide

Now there is a positive phase 3 trial with a TYK2/JAKi inhibitor. Presented at EULAR 2026 London, Brepocitinib dual TYK2/JAK1 inhibitor with successful Phase 3 VALOR trial demonstrating significant improvement in skin and muscle symptoms in dermatomyositis (DM). Previously presented, this abstract showed in 241 dermatomyositis patients, Brepocitinib 30mg a day demonstrated superiority over placebo with mandatory steroid reduction and 22% more achieved a total improvement score of >40.^1,2

Many MOAs in inflammatory myositis^3,4:
FcRn blockers
Efgartigimod sc FcRn blocker that reduces pathogenic IgG autoantibodies. Positive Phase 2 results in 2024 showed improvement in muscle strength and daily function across multiple subtypes (DM, PM, IMNM in Phase 2/3 ALKIVIA trial
Neopallia A FcRn blocker is being studied in IM.
Nipocalimab – insufficient enrolment so trial was stopped prematurely, I don’t know if another study will be designed with less difficult enrolment?

Other MOAs being studied in inflammatory myositis^3,4
Dazukibart reduces interferon-beta signaling in Phase 3 trials for dermatomyositis and polymyositis
Anifrolumab type I interferon receptor antagonist being evaluated for moderate-to-severe IIM
Enpatoran Toll-like receptor (TLR) 7/8 inhibitor being studied in Phase 2 trials to reduce inflammation in DM and PM
CABA-201 4-1BB-containing CD19-CAR T cell therapy designed for the potential "one-and-done" treatment of autoimmune diseases, including myositis
Apremilast: A PDE-4 inhibitor showing potential for refractory cutaneous dermatomyositis.
Daxdilimab: An anti-ILT7 monoclonal antibody targeting plasmacytoid dendritic cells, currently in trials for DM and anti-synthetase syndrome
Umbilical Cord Lining Stem Cells (ULSC)

Strong hope to strengthen patients!

References

1. Paik J, et al. BREPOCITINIB DEMONSTRATES CONSISTENT BENEFIT ON COMBINED MEASURES OF CLINICAL RESPONSE AND SUSTAINED CORTICOSTEROID TAPERING IN DERMATOMYOSITIS PATIENTS AT ONE YEAR. EULAR 2026, London., POS0264; 

2. Vleugels RA, et al. N Engl J Med. 2026;394:1883−93

3.Paik JJ, Werth VP, Chinoy H, Masri KR, Jambekar A, Hasan F, Borlenghi CE, Gold DA. Treatment guidelines for idiopathic inflammatory myopathies in adults: a comparative review. Rheumatology (Oxford). 2025 Jun 1;64(6):3288-3302.

4. Barsotti S, Lundberg IE. Current Treatment for Myositis. Curr Treatment Opt Rheumatol. 2018;4(4):299-315.