Table 4.
Results from mixed models evaluating the impact of treatment class on disease burden, disproportionate pain, and disease activity among combination therapy initiators
| Outcomes | Six-month mean (SD)/response rate | Unadjusteda | Adjustedb | |||||
|---|---|---|---|---|---|---|---|---|
| TNFi | IL-6Ri | βc | ORc | 95% CI | βc | ORc | 95% CI | |
| Disease activity | ||||||||
| CDAI | 16.7 (12.3) | 18.7 (13.6) | 1.12 | − | -0.17, 2.40 | 0.48 | − | -0.84, 1.81 |
| Achievement of LDA | 478/1301 (36.7%) | 124/397 (31.2%) | − | 0.81 | 0.56, 1.18 | − | 0.96 | 0.66, 1.38 |
| Achievement of remission | 114/1301 (8.8%) | 31/397 (7.8%) | − | 1.43 | 0.42, 4.86 | − | 1.23 | 0.34, 4.44 |
| Achievement of MCID in CDAI | 605/1301 (46.5%) | 185/397 (46.6%) | − | 0.89 | 0.66, 1.20 | − | 0.97 | 0.71, 1.30 |
| Disease burden | ||||||||
| HAQ-DI | 1.0 (0.7) | 1.1 (0.7) | 0.03 | − | -0.02, 0.09 | 0.01 | − | -0.05, 0.07 |
| HAQ-DI improvement ≥ 0.22 | 456/1168 (39.0%) | 142/382 (37.2%) | − | 0.82 | 0.59, 1.15 | − | 0.89 | 0.63, 1.25 |
| HAQ-DI improvement ≥ 0.30 | 348/1168 (29.8%) | 111/382 (29.1%) | − | 0.87 | 0.59, 1.28 | − | 0.98 | 0.66, 1.46 |
| Pain VAS | 45.3 (28.4) | 47.8 (27.5) | 0.97 | − | -1.81, 3.76 | 0.21 | − | -2.66, 3.08 |
| Pain VAS improvement ≥ 10 | 611/1308 (46.7%) | 181/401 (45.1%) | − | 0.78 | 0.54, 1.11 | − | 0.82 | 0.56, 1.18 |
| Patient global assessment VAS | 42.0 (26.6) | 45.5 (27.0) | 1.73 | − | -0.95, 4.41 | 1.30 | − | -1.44, 4.04 |
| Patient global assessment VAS improvement ≥ 10 | 656/1306 (50.2%) | 191/400 (47.8%) | − | 0.72 | 0.49, 1.05 | − | 0.74 | 0.51, 1.08 |
| Fatigue VAS | 46.4 (29.1) | 49.3 (29.1) | 1.18 | − | -1.64, 3.99 | 1.13 | − | -1.77, 4.03 |
| Fatigue VAS improvement ≥ 10 | 509/1165 (43.7%) | 175/379 (46.2%) | − | 1.02 | 0.74, 1.41 | − | 0.99 | 0.71, 1.38 |
| EQ-5D | 0.7 (0.2) | 0.7 (0.2) | -0.00 | − | -0.02, 0.01 | -0.00 | − | -0.02, 0.02 |
| DP | ||||||||
| DP1: All initiators | 165/1310 (12.6%) | 71/398 (17.8%) | − | 1.64 | 1.10, 2.45 | − | 1.39 | 0.94, 2.06 |
| DP1 at baseline, no DP1 at 6 months | 160/258 (62.0%) | 51/87 (58.6%) | − | 0.83 | 0.42, 1.63 | − | 0.93 | 0.45, 1.89 |
| DP2: All initiators | 332/978 (33.9%) | 115/311 (37.0%) | − | 1.16 | 0.78, 1.73 | − | 1.06 | 0.70, 1.61 |
| DP2 at baseline, no DP2 at 6 months | 112/287 (39.0%) | 38/100 (38.0%) | − | 0.90 | 0.44, 1.88 | − | 1.00 | 0.47, 2.12 |
aUnadjusted models include treatment indicators and baseline value of outcome as independent variables
bAdjusted models include treatment indicators, baseline value of outcome, and covariates specified in the covariate list and those identified to be significantly different in baseline table (covariates of monotherapy initiators: biologic line of therapy, age, duration of RA, gender, work status, history of CVD, CDAI, and morning stiffness; covariates of combination therapy initiators: biologic line of therapy, history of CVD, CDAI, patient reported pain, prior use of csDMARDs, and opioids use.)
cBased on unadjusted and covariate-adjusted regression analyses (β [95% CI] for linear regressions and OR [95% CI] for logistic regressions) using TNFi group as the reference; β represents the expected difference in the mean change of outcomes from baseline to 6 months for IL-6i group compared to TNFi group
CDAI, clinical disease activity index; csDMARDs, conventional synthetic disease modifying anti-rheumatic drugs; CI, confidence interval; CVD, cardiovascular disease; DP, disproportionate pain; EQ-5D, EuroQol-5 Dimension score; HAQ-DI, Health Assessment Questionnaire-Disability Index; IL-6i, interleukin-6 receptor inhibitor; LDA, low disease activity; MCID, minimal clinically important difference; OR, odds ratio; RA, rheumatoid arthritis; SD, standard deviation; TNFi, tumor necrosis factor inhibitor; VAS, visual analog scale