Table 2.

Disease-modifying antirheumatic drugs (DMARDs) initiation^*

Recommendations	Certainty of evidence	Based on the evidence report(s) of the following PICO(s)†	Evidence table(s), in Supp. App. 2
Initiation of treatment in DMARD-naive patients with moderate-to-high disease activity
Methotrexate monotherapy is strongly recommended over:
Hydroxychloroquine or sulfasalazine	Very low/low‡	PICO 2a.C1/C2	p. 14–5
bDMARD or tsDMARD monotherapy	Very low/moderate	PICO 5a.C1–4/C5§	p. 61–78
Combination of methotrexate plus a non–TNF inhibitor bDMARD or tsDMARD¶	Low/very low	PICO 6a.C2–4/C5§	p. 109, 117–28
Methotrexate monotherapy is conditionally recommended over:
Leflunomide	Low	PICO 2a.C3	p. 18
Dual or triple csDMARD therapy¶	Moderate	PICO 4a.C1–C2	p. 46–9
Combination of methotrexate plus a TNF inhibitor¶	Low	PICO 6a.C1	p. 110
Initiation of a csDMARD without short-term (<3 months) glucocorticoids is conditionally recommended over initiation of a csDMARD with short-term glucocorticoids.	Very low	PICO 7a	p. 167
Initiation of a csDMARD without longer-term (≥3 months) glucocorticoids is strongly recommended over initiation of a csDMARD with longer-term glucocorticoids.	Moderate	PICO 8a	p. 170
Initiation of treatment in DMARD-naive patients with low disease activity
Hydroxychloroquine is conditionally recommended over other csDMARDs.	Very low	PICO 1a.C1–4	p. 1–6
Sulfasalazine is conditionally recommended over methotrexate.	Very low	PICO 1a.C2	p. 2
Methotrexate is conditionally recommended over leflunomide.	Very low	PICO 1a.C3	p. 5
Initiation of treatment in csDMARD-treated, but methotrexate-naive, patients with moderate-to-high disease activity#
Methotrexate monotherapy is conditionally recommended over the combination of methotrexate plus a bDMARD or tsDMARD.**	Moderate/very low	PICO 6b.C1–4/C5§	p. 136–56

^*PICO = population, intervention, comparator, and outcomes; Supp. App. 2 = Supplementary Appendix 2, available on the Arthritis Care & Research website at http://onlinelibrary.wiley.com/doi/10.1002/acr.24596/abstract; bDMARD = biologic DMARD; tsDMARD = targeted synthetic DMARD; TNF = tumor necrosis factor; csDMARD = conventional synthetic DMARD.

^† The closest matching PICO questions to each recommendation are provided.

^‡The first certainty of evidence applies to the first listed option; the second certainty of evidence applies to the second listed option.

^§The original PICO included individual DMARDs as comparators. The recommendation considers bDMARDs as a group.

^¶The direction of the beneficial effect is in favor of the nonpreferred option.

^#Other recommendations for this patient population are the same as those for DMARD-naive patients.

^**The direction of the beneficial effect is in favor of the nonpreferred option. The certainty of evidence is high for the combination of methotrexate plus a TNF inhibitor and moderate for other bDMARDs.