| Outcome Type | Specific Outcome | Results | Strength of Evidence | Summary of Rationale for Strength of Evidence |
|---|---|---|---|---|
| Disease activity | Responsea | No significant difference between SSZ + MTX and MTX alone4, 21–25 | Low for trials | Downgraded because open label design; high attrition; large CIs cross appreciable benefits or harms; and not enough events to meet optimal information size |
| Disease activity | Responsea | SSZ + MTX and MTX alone26 | Insufficient for obs evidence | Downgraded because high attrition; large CIs cross appreciable benefits or harms; and not enough events to meet optimal information size |
| Disease activity | Responsea | SSZ compared with MTX, with or without concomitant PNL27, 28 | Insufficient for both trials and obs evidence | Trials: Downgraded because high attrition; large baseline differences between groups; large CIs cross appreciable benefits or harms; and not enough events to meet optimal information size Obs evidence: Downgraded because high attrition; large CIs cross appreciable benefits or harms; and not enough events to meet optimal information size |
| Disease activity | Responsea | TOF compared with MTX alone29 | Insufficient | Downgraded because high attrition; large CIs cross appreciable benefits or harms; and not enough events to meet optimal information size |
| Disease activity | Remission | SSZ compared with MTX, with concomitant PNL27 | Insufficient | Downgraded because high attrition; direction of effect varies; large CIs cross appreciable benefits or harms; and not enough events to meet optimal information size |
| Disease activity | Remission | TOF compared with MTX alone29 | Insufficient | Downgraded because high attrition; large CIs; and not enough events to meet optimal information size |
| Disease activity | Radiographic Changes | SSZ compared with MTX, with or without concomitant PNL27 | Insufficient | Downgraded because high attrition; large baseline differences between groups; large CIs cross appreciable benefits or harms; and not enough events to meet optimal information size |
| Disease activity | Radiographic Changes | SSZ + MTX and MTX alone4, 21, 22, 24, 25 | Insufficient | Downgraded because high attrition; large CIs cross appreciable benefits or harms; and not enough events to meet optimal information size |
| Disease activity | Radiographic Changes | TOF compared with MTX29 | Insufficient | Downgraded because high attrition; large CIs cross appreciable benefits or harms; and not enough events to meet optimal information size |
| Functional Capacity | N/A | No significant difference between SSZ + MTX and MTX alone4, 21–25 | Low | Downgraded because open label design; high attrition; and large CIs cross appreciable benefits or harms |
| Functional Capacity | N/A | No significant difference between PNL + MTX + SSZ + HCQ and monotherapy with MTX or SSZ22 | Low | Downgraded because open label design; high attrition; and large CIs cross appreciable benefits or harms |
| Functional Capacity | N/A | SSZ compared with MTX, with or without concomitant PNL27 | Insufficient for both trials and obs evidence | Trials: Downgraded because high attrition; not enough events to meet optimal information size; and large baseline differences between groups Obs evidence: Downgraded because high risk of confounding by indication |
| Functional Capacity | N/A | TOF compared with MTX alone29 | Insufficient | Downgraded because large CIs cross appreciable benefits or harms, and not enough events to meet optimal information size |
| Harms | SAEs and D/C attributable to AEs | No significant differences between SSZ + MTX and MTX alone4, 21–25 | Low for trials | Downgraded because open label design; high attrition; and imprecision |
| Harms | D/C attributable to AEs | SSZ + MTX and MTX alone26 | Insufficient for obs evidence | Downgraded because of high risk of selection bias for treatment discontinuation; high risk of confounding by indication; and not enough events to meet optimal information size |
| Harms | SAEs and D/C attributable to AEs | TOF compared with MTX29 | Insufficient | Downgraded because high attrition; large CIs cross appreciable benefits or harms; and not enough events to meet optimal information size |
| Harms | D/C attributable to AEs | SSZ compared with MTX, with or without concomitant PNL27, 28 | Insufficient for both trials and obs evidence | Trials: Downgraded because high attrition; large CIs cross appreciable benefits or harms; and not enough events to meet optimal information size Obs evidence: Downgraded because high risk of confounding by indication; large CIs cross appreciable benefits or harms; and not enough events to meet optimal information size |
Response defined by ACR or DAS28
ACR = American College of Rheumatology; AE = adverse event; CI = confidence interval; csDMARD = conventional synthetic disease modifying anti-rheumatic drug; D/C = discontinuation; DAS28 = Disease Activity Score based on 28 joints; HCQ = hydroxychloroquine; MTX = methotrexate; N/A = not applicable; Obs = observational; PNL = prednisolone; PRED = prednisone; SAE = serious adverse event; SSZ = sulfasalazine; TOF = tofacitinib; tsDMARD = targeted synthetic DMARD.
From: Evidence Summary
NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.