Table 3.

Characteristics of included studies

Reference	Design	Country of origin	N	Inclusion criteria	Outcome a	Follow up
[18] b	Prospective	The Netherlands	113	JIA, starting MTX	1k, 2a, 2d, 2f	1 y
[19]	Prospective	UK	87	JIA, starting MTX	1b, 1j	6 mo
[17] c	Retrospective and prospective	The Netherlands	287	JIA, starting MTX	1c	1 y
[10]	Retrospective	Germany	411	JIA, starting MTX	1a, 1b, 1c, 2i	1 y
[16] (deriv)	Retrospective	The Netherlands	183	JIA, starting MTX	1e	1 y
[16] (rep)	Prospective	The Netherlands	104	JIA, starting MTX	1e	1 y
[23] (deriv)d	Prospective	UK	197	JIA, starting MTX	1d	6 mo
[23] (rep)d	Unknown	USA	210	JIA, starting MTX	1g	6 mo
[31]	Cross-sectional	Japan	92	JIA, at least 3 mo MTX	2e	Mean 58.2 moe
[24] (deriv)d	Prospective	UK	197	JIA, starting MTX	1d	6 mo
[24] (rep)d	Unknown	USA	210	JIA, starting MTX	1g	6 mo
[20]	Cross-sectional	Czech Republic	69	JIA, at least 3 mo MTX	1i, 2d, 2f, 2g, 2h	Median 1.3-1.4 ye
[28] f	Prospective	Multinational (PRINTO)	563	RF negative polyarticular course JIA, starting MTX	1a, 1c	6 mo
[26]	Prospective	Italy	60	JIA, ≥2 active joints in oligo persistent, ≥5 active joints in other categories	1b	1 y
[27] f	Prospective	Multinational (PRINTO)	521	RF negative polyarticular course JIA, starting MTX	1l	6 mo
[25]	Retrospective	Italy	125	Polyarticular JIA, starting MTX	1f, 1i	6 mo, 5 y
[32]	Retrospective	Germany	58	JIA, at least 3 mo MTX	2d, 2i	Mean 48 months
[21]	Retrospective	Italy	80	JIA, at least 6 mo MTX	1a, 2c, 2g	Efficacy: 6 mo
						Toxicity: median 6–9 mo
[29]	Retrospective	USA	49	JRA, starting MTX	1h	Mean 2.6 y (range 1.0-7.3 y)
[34] b	Prospective	The Netherlands	152	JIA, starting MTX	2b	1 y
[22]	Retrospective and prospective	Czech Republic, UK, The Netherlands	694	JIA, starting MTX	1f	6 mo

Abbreviations: ACR30/50/70 American College of Rheumatology pediatric 30, 50 or 70 response criteria, respectively, AE adverse event, ALT alanine aminotransferase, AST aspartate aminotransferase, CHQ child health questionnaire, deriv derivation cohort, GI gastrointestinal, HRQOL health-related quality of life, JADAS juvenile arthritis disease activity score, JIA juvenile idiopathic arthritis, min minutes, MISS methotrexate intolerance severity score, mo months, MTX methotrexate, NR non-response, PhS physical component summary score, PsS psychosocial component summary score, RA rheumatoid arthritis, rep replication cohort, RF rheumatoid factor, ULN upper limit of normal, y years.

^a 1a: Achievement of ACR30; 1b: Achievement of ACR50; 1c: Achievement of ACR70; 1d: Achievement of ACR70 vs. non-achievement of ACR30; 1e: Achievement of ACR70 in 2/3 visits; 1f: NR vs. ACR30 vs. ACR50 vs. ACR70; 1g: >70% improvement in joint count vs. <30%; 1h: Adapted ACR criteria for RA: morning stiffness <15 min, no fatigue, no joint swelling, no joint pain for 2 consecutive months; 1i: Clinical inactive disease on MTX monotherapy according to Wallace criteria; 1j: JADAS-10; 1k: JADAS-27; 1l: HRQOL: CHQ PhS ≥30 and PsS ≥30; 2a: MISS: intolerant (score >6); 2b: MISS: intolerant (score >6) after 6 and/or 12 months; 2c: ALT/AST > ULN; 2d: ALT/AST >2 ULN; 2e: ALT >5 ULN; 2f: Bone marrow suppression (any cytopenia); 2g: GI toxicity; 2h: Other (alopecia, headaches, behavioural changes, nodulosis); 2i: Any AE; ^bThis is the same cohort as the replication cohort of [16], but different outcome and/or predictors; ^cThis cohort is the derivation and replication cohort of [16] together, but uses a slightly different outcome and different predictors; ^dThese are the same cohorts, but they use different predictors; ^eTime after start of MTX; ^fThese are the same cohorts, but they use different outcome measurements.