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mapped to ≥1 PICO questions addressing pharmacologic treatment (see Supplementary Appendix 6, available on the Arthritis Care & Research website at http://onlinelibrary.wiley.com/doi/10.1002/ acr.24596/abstract). The literature review did not identify any evidence for 41% (n = 33) of the PICO questions. Recommendations for DMARD-naive patients with moderate-to-high disease activity (Table 2) DMARD monotherapy Methotrexate is strongly recommended over hydroxychloroquine or sulfasalazine for DMARDnaive patients with moderate-to-high disease activity This recommendation is strongly in favor of methotrexate despite very low-certainty evidence for hydroxychloroquine and low-certainty evidence for sulfasalazine based on the amount of data supporting the disease-modifying properties of methotrexate monotherapy compared to hydroxychloroquine or sulfasalazine and concerns over the long-term tolerability of sulfasalazine (13,14). Methotrexate is conditionally recommended over leflunomide for DMARD-naive patients with moderate-to-high disease activity Despite low-certainty evidence of comparable efficacy, methotrexate is preferred over leflunomide because of the evidence supporting its value as an anchor DMARD in combination regimens. Additional advantages of methotrexate include its greater dosing flexibility and lower cost. Methotrexate monotherapy is strongly recommended over bDMARD or tsDMARD monotherapy for DMARD-naive patients with moderate-to-high disease activity There is low-certainty evidence suggesting superiority of tocilizumab monotherapy (15) over methotrexate monotherapy and moderate-certainty evidence suggesting greater efficacy 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 (12 months prior to considering a change. Addition of/switching to DMARDs is conditionally recommended over initiation/dose escalation of glucocorticoids for patients with a serious infection within the previous 12 months who have moderate-to-high disease activity This conditional recommendation is made based on observational studies suggesting a strong association between dose and duration of glucocorticoids with the risk of serious infection (51–53). Nontuberculous mycobacterial (NTM) lung disease Given the variability of NTM lung disease severity and response to treatment, patients should be closely comanaged with an infectious disease or pulmonary specialist. Use of the lowest possible dose of glucocorticoids (discontinuation if possible) is conditionally recommended over continuation of glucocorticoids without dose modification for patients with NTM lung disease This recommendation is based on studies suggesting an increased risk of NTM lung disease in patients receiving either inhaled or oral glucocorticoids (54,55). Addition of csDMARDs is conditionally recommended over addition of a bDMARD or tsDMARD for patients with NTM lung disease
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