Compare by TIS
The Total Improvement Score (TIS) used in modern idiopathic inflammatory myopathy (IIM) trials is the 2016 American College of Rheumatology/European League Against Rheumatism myositis response criteria composite, a 0–100 scale built from 6 weighted core set measures (strength/MMT-8, physician & patient global activity, HAQ, extramuscular activity, muscle enzymes). Minimal, moderate, and major improvement are typically TIS ≥20, ≥40, and ≥60, respectively. In placebo-controlled trials that explicitly used TIS as a main endpoint, the most convincing efficacy signals come from IVIG in dermatomyositis (ProDERM) and brepocitinib in dermatomyositis (VALOR)—but cross-trial “most effective” rankings are inherently imperfect because trials differ in entry criteria, background immunosuppression, rescue rules, and whether they analyze responder rates (e.g., TIS≥20) vs mean TIS at different timepoints. Also, TIS is more heavily influenced by muscle improvement, which can disadvantage therapies (or patient subsets) where skin-dominant disease is the main issue—something highlighted directly in the lenabasum Phase 3 readout.
Head-to-head style comparison of key IIM trials using TIS
| IVIG (octagam 10%) (sponsor: Octapharma) | ProDERM (adult DM) | Phase 3, randomized, placebo-controlled; primary at Week 16 | Primary endpoint: TIS ≥20 (minimal improvement) without deterioration | Positive: Week 16 minimal response 79% vs 44%; mean TIS 48 vs 21; moderate/major responses also higher on IVIG. |
| Brepocitinib (TYK2/JAK1)(sponsors: Roivant Sciences / Priovant Therapeutics) | VALOR (adult DM) | Phase 3, randomized, placebo-controlled; 52 weeks | Primary endpoint: mean TIS at Week 52vs placebo | Positive: Week 52 mean TIS 46.5 vs 31.2 (p=0.0006); also large proportions reaching TIS≥40 and ≥60 per topline report. |
| Tocilizumab | Refractory adult DM/PM (phase 2B) | Randomized, placebo-controlled; 24 weeks | Primary: TIS comparison over treatment phase | Negative: no difference in TIS over 24 weeks; mean on-treatment TIS ~26.4 (tocilizumab) vs 29.3(placebo). |
| Lenabasum(sponsor: Corbus Pharmaceuticals) | DETERMINE (adult DM) | Phase 3, randomized, placebo-controlled; primary at Week 28 | Primary: mean TIS at Week 28 | Negative: Week 28 mean TIS 28.3 vs 26.7 (p=0.1965); subtype signals noted, and sponsor commentary emphasizes TIS weighting toward muscle. |
| Abatacept | Active IIM (DM + non-DM subtypes incl PM/IMNM) | Phase 3 randomized controlled; 24 weeks double-blind | Secondary/exploratory: mean TIS and response categories | Mixed/weak: mean TIS change at week 24 40.8 vs 37.2 (difference 3.6; CI crosses 0); signal more apparent in non-DM subgroup than DM. |
| Zetomipzomib (KZR-616) (sponsor: Kezar Life Sciences) | PRESIDIO (active DM/PM) | Phase 2 randomized, placebo-controlled crossover; 16 weeks per period | Primary: mean change in TIS | Negative: Week 16 mean TIS 25.5 vs 25.0; no differentiation from placebo in crossover readout. |
| Efgartigimod PH20 SC (sponsor: argenx) | ALKIVIA (active IIM; DM/ASyS/IMNM included) | Phase 2 portion reported; primary at Week 24 | Primary: mean TIS at end of treatment; also reports across core set measures | Signal reported in Phase 2 analyses with improvement in several core measures vs placebo; detailed peer-reviewed manuscript results are still emerging. |
So…which looks “most effective” by TIS?
If you restrict the question to placebo-controlled trials that use TIS as a central outcome, the strongest demonstrated efficacy signals are:
- IVIG in adult dermatomyositis (ProDERM): large early separation on both TIS≥20 responder rate and mean TIS by Week 16.
- Brepocitinib in dermatomyositis (VALOR): clear separation on mean TIS at Week 52 with statistically robust topline results in a year-long placebo-controlled design.
Everything else above is negative (tocilizumab, lenabasum, zetomipzomib) or mixed/early (abatacept subgroup-leaning; efgartigimod Phase 2 signal pending full publication).