Studies reporting the efficacy and/or safety of GCs, csDMARDs, MTX and CsA colchicine and IVIG in sJIA and AOSD
| First author | Study design | Patients (N) | Intervention | Concomitant treatment | CID (%) | Other outcomes (%) | AE * | SAE* | Risk† | |
| GCs | Picco29 | RCT | sJIA (12) | MPDN intravenous 5 mg/kg/day for 3 days, then 2.5 mg/kg/days for 3 days, then PDN per os (1 mg/kg/day) for 6 months | NSAIDs | na | 11/12 (92%) ‡ | 5 | na | |
| sJIA (10) | PDN 1 mg/kg/day for 6 months | NSAIDs | na | 9/10 (90%) | ||||||
| Adebajo30 | LOR | sJIA (18) | MPDN pulses (8 one pulse, 7 two pulses and 4 three pulses) | Other GCs, NSAIDs and csDMARDs | 10 (55%)§ CRM: 3 (16%) for 24 months | na | Two avascular necrosis hip and hip replacement | |||
| Ruscitti31 | LOP | AOSD (80) 50% on low dose (LD); 50% on high dose regimen (HD) | HD: PDN 0.8–1 mg/kg/day LD: PDN 0.2–0.3 mg/kg/day | na | Overall: 33/73 (45%) HD 25/38 (65%) LD 8/35 (23%) | na | (7%) | 5 (6%) MAS: 1 (2%) on HD and 4 (10%) on LD | ||
| MTX | Fujii36 | LOR | AOSD (13) | MTX 5–20 mg/week for 4 months | GCs | 8/13 (61%) | na | 5/13 (38%) patients | ||
| Al-Sewairy37 | LOR | sJIA (18) | MTX 2.5–15 mg/week for 18 months | GCs | na | 16 (89%) ¶ CRM: 7 (39%) at 12 M | na | na | ||
| Woo39 | RCT | sJIA (45) | MTX PO 15–20 mg/m2 | GCs and NSAIDs | na | ACR30 (25%) | 57 | One pneumonitis | ||
| sJIA (44) | PBO | GCs and NSAIDs | Na | ACR30 (16%) | 63 | Two pneumonitis | ||||
| Fautrel38 | LOR | AOSD (26) | MTX 10 mg/week for 8–136 months | GCs | 18 (69%) | na | 14 | One AA amyloidosis and severe neutropenia (died) seven GCs related | ||
| Multiple csDMARDs interventions and CsA | Mitamura41 | LOR | AOSD (34) | CsA 7 (21%) 125 mg/day to 200 mg/day for 12.4 months (1–31) MTX 10 (29%) 5–8 mg/week | GCs, 13 (38%): CYC, FK506, AZA, Gold, D-PEN, SSZ, colchicine and mizoribine | 6/7 (86%) on CsA 1/10 (10%) on MTX | na | 0 | On CsA: one brain nocardiosis, pericarditis, interstitial pneumonia,one lung nocardiosis and one MAS+DIC | |
| Franchini28 | LOR | AOSD (45) | MTX 22 courses (49) up to 25/mg week for 56 months CsA 12 courses (27) up to 250 mg/day for 56 months | GCs NSAIDs, AZA, SSZ | 16/22** (73%) MTX 9/12 (75%) CsA 3/4 (75%) AZA | na | na | na | ||
| CsA | Pal40 | LOP | sJIA (15) | CsA 3.1 mg/kg/day for 12 months | GCs, MTX | M2: 13/15 (86.6%) †† At 5 years: 11 (73%) | na | 2 | 0 | |
| Colchicine | Myachikova‡‡32 | LOR | AOSD (20) with serositis | Colchicine 1 mg/day | NSAIDs and GCs | 13 (65%) | na | 6 | 0 | |
| IVIGs | Silverman33 | RCT | sJIA (14) | IVIG 1.5 g/kg (maximum 75 g) every 2 weeks for 2 months, then monthly for 4 months | NSAIDs and GCs | na | 7/14 (50%)§§ 7/14 (50%)¶¶ 14/47 (30%)*** | 10 | 0 | |
| sJIA (17) | PBO | NSAIDs and GCs | na | 4/15 (27%)§§ 7/14 (50%)¶¶ 22/48 (46%)*** | 0 | 0 | ||||
| Uziel34 | LOR | sJIA (27) | IVIG 1 g/kg/day for 2 days, then 1.5 g/kg/day 1 day (2–102 months) | NSAIDs, GCs, MTX (six patients) | 4/25 (16%)††† | 0 | One septic meningitis, one MPGN, one SLE and one necrotising vasculitis | |||
| Gerfaud-Valentin35 | LOR | AOSD (23) | IVIG (dose not specified) | na | na | 4/23 (17%)‡‡‡ | One acute renal failure | |||
| Néel132 | LOR | AOSD (6) | IVIG 2 g/kg/day | GCs | na | 1/6 (17%)§§§ | na | na |
*AE only number is reported (% of patients). For SAE, individual SAEs are listed. Infection events are also listed.
†RoB was calculated with RoB-2 tool; red=high, yellow=intermediate and green=low.
‡The outcome of efficacy is expressed as ‘decrease in fever and disease activity score’.
§Normalisation of systemic features.
¶The response to MTX was evaluated in all patients and was defined as a reduction of 50% or more in the number of joints with active arthritis and control of all systemic features; the response was defined as ‘clinical improvement’.
**22 refers to the total drug courses.
††Classified as responders off CsA and GCs;.
‡‡Colchicine in this study was employed for the specific manifestation of pericarditis in AOSD. Remission in this study was defined if persistent apyrexia, absence of rash, absence of articular syndrome and sore throat, pericardial effusion less than 7 mm according to transthoracic echocardiography, absence of chest pain, CRP level less than 5 mg/L, normalisation of aminotransferases, leucocyte count and ferritin level.
§§Better, much better according to Physician Global Assessment.
¶¶Clinically important improvement in severity score (articular).
***Improvement on the total number of laboratory tests executed. Improvement is expressed as: ‘at least 25% improvement or normalisation in haemoglobin, albumin and platelet count and ESR’.
†††Remission expressed as ‘no active joints’.
‡‡‡IVIG ‘controlled the disease’.
§§§In this study, IVIG were used in second line in ICU patients and the outcome is defined as ‘efficacy’.
ACR, American College of Rheumatology; AE, adverse events; ALT, alanine aminotransferase; AOSD, adult-onset Still’s disease; AP, alkaline phosphatase; AZA, azathioprine; CID, clinical inactive disease; CRM, clinical remission on medication; CRP, C reactive protein; CsA, ciclosporin A; csDMARDs, conventional synthetic disease-modifying antirheumatic drug; CYC, cyclophosphamide; DIC, disseminated intravascular coagulation; D-PEN, D-penicillamine; ESR, erythrocyte sedimentation rate; FK506, tacrolimus; GCs, glucocorticoids; ICU, intensive care unit; IVIG, intravenous immunoglobulins; LOP, longitudinal observational prospective; LOR, longitudinal observational retrospective; M, months; MAS, macrophage activation syndrome; MPDN, methylprednisolone; MPGN, membranoproliferative glomerulonephritis; MTX, methotrexate; NSAIDs, non-steroidal anti-inflammatory drugs; PBO, placebo; PDN, prednisone; PO, per os; RCT, randomised controlled trial; RoB, risk of bias; SAE, severe adverse events; sJIA, systemic juvenile idiopathic arthritis; SLE, systemic lupus erythematosus; SSZ, sulfasalazine.