High correlation of VAS pain scores after 2 and 6 weeks of treatment with VAS pain scores at 12 weeks in randomised controlled trials in rheumatoid arthritis and osteoarthritis: meta-analysis and implications

Abstract

Background: Researchers in clinical trials in rheumatoid arthritis (RA) and osteoarthritis (OA) often measure pain levels with a visual analogue scale (VAS). Of interest to clinical practice and future clinical trial design are associations of change from baseline (CFB) between time points with predictive ability of earlier response for long-term treatment benefit. We assessed the association and predictive ability of CFB in VAS pain between 2, 6 and 12 weeks in randomised controlled trials (RCTs) of non-steroidal anti-inflammatory drugs (NSAIDs).

Methods: Aggregated VAS pain data at baseline and CFB at 2, 6 and 12 weeks were collected from a systematic literature review of 176 RCTs in OA and RA. The predictive ability of earlier assessments for longer-term pain reduction was estimated using correlation and regression analyses. Analysis was performed using the R software package for statistical programming, version 3.1.1.

Results: Appropriate data were available from 50 RCTs (22,854 patients). Correlations between time points were high (weighted correlation coefficients between 2 and 6 weeks, 0.84; between 2 and 12 weeks, 0.79; and between 6 and 12 weeks, 0.96). CFB at 6 weeks was highly predictive and close to CFB at 12 weeks (regression coefficient 0.9, 95 % confidence interval 0.9-1.0). CFB at 2 weeks was significantly associated with CFB at 12 (0.8, 0.7-0.8) and 6 weeks (0.9, 0.8-1.0).

Conclusions: The results showed that early analgesic response measured by VAS for pain beyond 2 weeks of treatment with a particular NSAID is likely to be predictive of response at 12 weeks. Failure to achieve desired pain relief in OA and RA after 2 weeks should trigger reassessment of dosage and/or analgesic.

Keywords: NSAID; Osteoarthritis; Rheumatoid arthritis; VAS pain.

Fig. 1

CFB in VAS pain 2-week data versus CFB in VAS pain 6-week data. A scatterplot of observed CFB data from RCT arms is displayed along with predicted regression lines, N-weighted (red line) and precision-weighted (blue line). AIC Akaike information criterion; CFB change from baseline, RCT randomised controlled trial, VAS visual analogue scale

Fig. 2

CFB in VAS pain 2-week data versus CFB in VAS pain 12-week data. A scatterplot of observed CFB data from RCT arms is displayed along with predicted regression lines, N-weighted (red line) and precision-weighted (blue line). AIC Akaike information criterion; CFB change from baseline, RCT randomised controlled trial, VAS visual analogue scale

Fig. 3

CFB in VAS pain 6-week data versus CFB in VAS pain 12-week data. A scatterplot of observed CFB data from RCT arms is displayed along with predicted regression lines, N-weighted (red line) and precision-weighted (blue line). AIC Akaike information criterion; CFB change from baseline, RCT randomised controlled trial, VAS visual analogue scale