Univariate analysis of individual covariates of immune-mediated adverse event risk and risk of TNFi in association with event
| HR (95% CI) for covariate | HR (95% CI) for anti-TNF agent | |
|---|---|---|
| Lupus-like events | ||
| Unadjusted | 3.88 (1.54 to 9.23) | |
| Age (per year) | 0.98 (0.97 to 1.01) | 3.79 (1.51 to 9.53) |
| Gender (male referent) | 2.74 (1.25 to 6.00)* | 3.83 (1.53 to 9.59) |
| Ethnicity (non-white referent) | 2.90 (1.24 to 6.75)* | 3.36 (1.34 to 8.43) |
| Rheumatoid factor-positive | 1.08 (0.75 to 1.55) | 3.91 (1.56 to 9.80) |
| Smoking (current smoking referent) | 0.96 (0.49 to 1.67) | 3.95 (1.57 to 9.88) |
| Disease duration | 1.01 (0.99 to 1.04) | 3.89 (1.55 to 9.77) |
| Baseline DAS28 | 1.58 (1.25 to 1.98)* | 2.38 (0.90 to 6.29) |
| Baseline HAQ score | 1.69 (1.11 to 2.56)* | 2.73 (1.07 to 6.97) |
| Comorbidities (nil referent) | ||
| 1 comorbidity | 1.11 (0.65 to 1.91) | 3.95 (1.58 to 9.90) |
| 2 comorbidities | 0.77 (0.34 to 1.75) | |
| ≥3 comorbidities | 1.17 (0.41 to 3.38) | |
| Methotrexate use† | 0.91 (0.54 to 1.51) | 3.92 (1.57 to 9.83) |
| Baseline methotrexate use | 1.03 (0.62 to 1.72) | 3.95 (1.58 to 9.88) |
| Sulfasalazine use† | 0.30 (0.12 to 0.75)* | 3.38 (1.34 to 8.51) |
| Baseline sulfasalazine use | 0.36 (0.16 to 0.84)* | 3.53 (1.41 to 8.87) |
| Leflunomide use† | 0.73 (0.29 to 1.82) | 3.92 (1.57 to 9.83) |
| Baseline leflunomide use | 0.83 (0.33 to 2.01) | 3.93 (1.56 to 9.84) |
| HCQ use† | 1.30 (0.70 to 2.45) | 4.10 (1.63 to 10.31) |
| Baseline HCQ use | 1.57 (0.86 to 2.89) | 4.02 (1.61 to 10.08) |
| Minocycline use† | 11.20 (1.55 to 80.81)* | 3.88 (1.55 to 9.72) |
| Baseline minocycline use | 14.31 (1.98 to 103.18)* | 3.88 (1.55 to 9.72) |
| On steroid at baseline | 0.83 (0.49 to 1.36) | 4.23 (1.68 to 10.62) |
| Vasculitis-like event | ||
| Unadjusted | 2.12 (1.20 to 3.74) | |
| Age | 1.01 (0.98 to 1.03) | 2.27 (1.28 to 4.03) |
| Gender (male referent) | 0.67 (0.46 to 1.0) | 2.15 (1.22 to 3.80) |
| Ethnicity (non-white referent) | 0.51 (0.12 to 2.08) | 2.17 (1.18 to 4.00) |
| Rheumatoid factor-positive | 1.82 (1.18 to 2.78)* | 2.04 (1.16 to 3.61) |
| Current smoking | 1.30 (0.86 to 1.98) | 2.14 (1.21 to 3.79) |
| Disease duration | 1.03 (1.01 to 1.04)* | 2.16 (1.20 to 3.90) |
| DAS score | 1.42 (1.20 to 1.68)* | 1.44 (0.77 to 2.69) |
| HAQ score | 1.65 (1.19 to 2.28)* | 1.78 (0.93 to 3.42) |
| Comorbidities (nil referent) | ||
| 1 comorbidity | 1.46 (0.98 to 2.19) | 2.11 (1.19 to 3.72) |
| 2 comorbidities | 0.69 (0.35 to 1.38) | |
| ≥3 comorbidities | 1.16 (0.48 to 2.61) | |
| Methotrexate use† | 0.68 (0.47 to 0.98)* | 2.07 (1.17 to 3.67) |
| Baseline methotrexate use | 0.79 (0.54 to 1.14) | 2.07 (1.17 to 3.66) |
| Sulfasalazine use† | 0.46 (0.29 to 0.82)* | 1.84 (1.03 to 3.24) |
| Baseline sulfasalazine use | 0.56 (0.33 to 0.97)* | 1.96 (1.10 to 3.47) |
| Leflunomide use† | 0.75 (0.38 to 1.48) | 2.10 (1.19 to 3.72) |
| Baseline leflunomide use | 0.61 (0.27 to 1.38) | 2.08 (1.18 to 3.68) |
| HCQ use† | 0.81 (0.46 to 1.41) | 2.11 (1.19 to 3.74) |
| Baseline HCQ use | 0.91 (0.51 to 1.62) | 2.11 (1.19 to 3.72) |
| Combination nbDMARDs (≥2, including methotrexate) | 0.66 (0.43 to 1.00) | 2.05 (1.16 to 3.63) |
| On steroid at baseline | 1.20 (0.82 to 1.75) | 2.07 (1.16 to 3.67) |
The association between candidate confounders and the outcome (first lupus/vasculitis-like event), irrespective of the treatment group. The final column reports the effect of each baseline covariate on the estimated treatment effect.
*p<0.05.
†Use of nbDMARD versus not use during the study period (assumes the risk returns to baseline as soon as the patient is off the drug).
Anti-TNF, tumour necrosis factor-α inhibitor; DAS28, 28 joint count Disease Activity Score; HAQ, Health Assessment Questionnaire; nbDMARDs, non-biological disease-modifying antirheumatic drugs.