Use of corticoids and non-steroidal anti-inflammatories in the treatment of rheumatoid arthritis: Systematic review and network meta-analysis

Abstract

Evidence on the use of non-steroidal anti-inflammatory drugs (NSAIDs) and corticoids for rheumatoid arthritis (RA) is inconclusive and is not up to date. This systematic review assessed the effectiveness and safety of these anti-inflammatories (AI) in the treatment of RA. COCHRANE (CENTRAL), MEDLINE, EMBASE, CINAHL, Web of Science and Virtual Health Library were searched to identify randomized controlled trials (RCT) with adults which used AI (dose represented in mg/day) compared with placebo or active controls and was carried out up to December of 2019. Reviewers, in pairs and independently, selected studies, performed the data extraction and assessed the risk of bias. The quality of the evidence was assessed by GRADE. Network meta-analyses were performed using the Stata v.14.2. Twenty-six articles were selected (NSAIDs = 21 and corticoids = 5). Naproxen 1,000 improved physical function, reduced pain and the number of painful joints compared to placebo. Etoricoxib 90 reduced the number of painful joints compared to placebo. Naproxen 750 reduced the number of swollen joints, except for etoricoxib 90. Naproxen 1,000, etoricoxib 90 and diclofenac 150 were better than placebo regarding patient assessment. Assessment physician showed that NSAIDs were better than placebo. Meta-analyses were not performed for prednisolone and prednisone. Naproxen 1,000 was the most effective drug and celecoxib 200 showed fewer adverse events. However, the low quality of the evidence observed for the outcomes with NSAIDs, the absence of meta-analyses to assess the outcomes with corticoids, as well as the risk of bias observed, indicate that future RCT can confirm such findings.

Fig 1. Study flowchart.

VHL: Virtual Health Library; WHO: World Health Organization; NSAIDs: Non-steroidal anti-inflammatory drugs; corticoids drugs.

Fig 2. Risk of bias for studies on non-steroidal anti-inflammatories (n = 21).

Fig 3. Evidence structure of eligible comparisons for network meta-analysis: Effectiveness outcomes.

A—Pain (9 studies, 10 non-steroidal anti-inflammatories—NSAIDs, 22 arms, 4,016 patients); B—Physical function (4 studies, 5 NSAIDs, 11 arms, 2,447 patients); C- Number of tender/painful joints (8 studies, 6 NSAIDs, 21 arms, 4,962 patients); D—Number of swollen joints (8 studies, 6 NSAIDs, 21 arms, 4,962 patients); E—Patient’s Global Assessment (6 studies, 6 NSAIDs, 17 arms, 4,152 patients); F—Physician’s Global Assessment (6 studies, 6 NSAIDs, 17 arms, 4,152 patients).

Fig 4. Comparative effectiveness outcomes between drugs using network meta-analysis.

Comparisons should be read from left to right. Standardized mean difference (SMD) for comparisons are located in the common cell between the column-defining and row-defining treatment. Numbers on highlighted background are statistically significant. A. Pain; B. Physical function; C. Number of tender/painful joints (upper right quarter) and number of swollen joints (lower left quarter); D. Patient’s global assessment (upper right quarter) and physician’s global assessment (lower left quarter).

Fig 5. Evidence structure of eligible comparisons for network meta-analysis: Adverse events.

Lines connect the interventions that have been studied in head-to-head (direct) comparisons in the eligible randomized controlled trials. The width of the lines represents the cumulative number of randomized controlled trials for each pairwise comparison and the size of every node is proportional to the number of randomized participants (sample size).

Fig 6. Comparative adverse events between drugs using network meta-analysis.

Comparisons should be read from left to right. Odds ratio for comparisons are located in the common cell between the column-defining and row-defining treatment. Numbers on highlighted background are statistically significant.

Fig 7. Risk of bias for studies on corticoids (n = 5).