| Therapy class | Agent / approach | Typical place in therapy | Key efficacy data | Steroid-sparing / discontinuation data | Safety / cautions |
|---|---|---|---|---|---|
| First-line symptomatic therapy | NSAIDs | Historically used for mild initial disease; now usually adjunctive rather than definitive monotherapy | Reviews note that treatment is "no longer limited to NSAIDs" because targeted biologics have improved outcomes; NSAID-only control is generally limited in systemic disease | No robust recent pooled discontinuation data identified | GI, renal, and cardiovascular toxicity; usually insufficient for severe systemic inflammation |
| First-line anti-inflammatory therapy | Glucocorticoids (systemic corticosteroids) | Standard initial therapy for most patients, especially systemic flares | In the US claims cohort, systemic glucocorticoids were used in 62.2% of patients; expert consensus recommends reducing glucocorticoid exposure where possible because of toxicity | 2024 expert recommendations explicitly prioritize glucocorticoid reduction and favor biologics over prolonged conventional treatment | Infection risk, metabolic toxicity, osteoporosis, diabetes, hypertension, mood effects; prolonged use strongly discouraged when steroid-sparing options are available |
| Conventional DMARD | Methotrexate | Common steroid-sparing csDMARD, especially for articular disease or maintenance | In the US claims cohort, MTX was used in 51.0%; in the 24-patient Spanish NGS cohort, conventional DMARDs were used in 70.8% overall | Used to reduce steroid dependence, but no pooled steroid discontinuation rate reported in recent meta-analysis | Hepatotoxicity, cytopenias, teratogenicity; requires laboratory monitoring |
| IL-1 inhibition | Anakinra | Preferred biologic option for systemic-predominant or refractory disease; often early-line biologic | 2024 meta-analysis: complete remission 73% (95% CI 58-84) across pooled studies | 2024 meta-analysis: corticosteroid discontinuation 47% (95% CI 18-78) | Generally favorable safety profile; injection-site reactions and infection risk; in MAS meta-analysis pooled MAS incidence among anakinra-treated cohorts was 1.50% (95% CI 0-3.36) |
| IL-1 inhibition | Canakinumab | Approved/used for refractory or relapsing disease, often after or instead of anakinra | 2024 meta-analysis: complete remission 77% (95% CI 29-97), though heterogeneity was high | 2024 meta-analysis: corticosteroid discontinuation 34% (95% CI 6-81) | Generally well tolerated in reviews; infection risk and cost/access are practical issues |
| IL-6 inhibition | Tocilizumab | Widely used for systemic and articular inflammation, especially after steroid/csDMARD failure | 2024 meta-analysis: complete remission 80% (95% CI 59-92), the highest pooled estimate among the three best-studied biologics | 2024 meta-analysis: corticosteroid discontinuation 57% (95% CI 29-81) | MAS can be diagnostically masked under IL-6 blockade; pooled MAS incidence in TCZ-treated cohorts was 14.01% (95% CI 4.51-23.51), significantly higher than with anakinra in one meta-analysis, likely influenced by baseline severity and confounding by indication |
| TNF inhibition | TNF-α inhibitors (class) | Generally considered later-line, more often for chronic articular phenotype than highly systemic disease | Reviews list TNF inhibitors as available biologic options, but recent evidence base is less robust than for IL-1/IL-6 blockade | No reliable pooled steroid discontinuation estimate identified in the retrieved recent literature | Infection risk, paradoxical inflammatory reactions; typically not favored over IL-1/IL-6 blockade for systemic disease |
| JAK inhibition | Baricitinib, ruxolitinib, tofacitinib, upadacitinib | Emerging option for difficult-to-treat or biologic-refractory Still disease | French retrospective series of 9 difficult-to-treat Still disease patients: 2/9 complete remission, 3/9 partial response, 4/9 treatment failure | Corticosteroids could be decreased but not stopped at last follow-up in the 9-patient JAK inhibitor series | Tolerance described as acceptable with no severe adverse events in that small series; class risks include infection, herpes zoster, thrombosis, and laboratory abnormalities |
| Biologic strategy overall | bDMARDs (especially IL-1 and IL-6 blockade) | Increasingly preferred over prolonged conventional therapy in expert algorithms | 2024 systematic review/meta-analysis concluded that evidence supports TCZ, anakinra, and canakinumab, although comparative effectiveness remains uncertain and randomized trials were underpowered | Complete remission and corticosteroid discontinuation rates were consistently substantial across pooled biologic studies | Heterogeneity is high because agents are used at different disease stages and in different phenotypes; careful monitoring for infection and MAS remains essential |
| Expert treatment strategy | Early biologic use with steroid minimization | Consensus-based modern management approach | 2024 expert Delphi panel reached consensus on 29 statements and preferred biologics over conventional treatment; IL-1 and IL-6 blockade were considered important therapeutic pillars | Tapering strategies were part of the consensus recommendations, with specific emphasis on limiting glucocorticoid burden | Requires phenotype-based selection, exclusion of infection/malignancy, and monitoring for severe complications such as MAS |


*Table: This table summarizes current treatment approaches for adult-onset Still disease, emphasizing the strongest recent evidence for IL-1 and IL-6 inhibitors, plus steroid-sparing outcomes and major safety considerations. It is useful for comparing first-line, conventional, and biologic/JAK-based strategies in modern AOSD management.*