Summary of evidence for treatment-related predictors of adherence to MTX
| Predictor | Study | N | Outcome | Unadjusted ES (95% CI)/univariate analyses | p Value | Adjusted ES (95% CI) | p Value |
|---|---|---|---|---|---|---|---|
| MTX dose | |||||||
| MTX 12.5–17.5 mg | de Thurah et al27* | 85 | Non-adherence (CQR ≤25th centile) at BL | PR 0.6 (0.2 to 1.5) | NS | PR 0.7 (0.3 to 1.7) | NS |
| >17.5 mg/week | de Thurah et al27* | 85 | Non-adherence (CQR ≤25th centile) at BL | PR 0.5 (0.2 to 1.7) | NS | PR 0.6 (0.1 to 2.4) | NS |
| MTX 12.5–17.5 mg | de Thurah et al27* | 65 | Non-adherence (CQR ≤25th centile) at 9 mo | PR 0.2 (0.0 to 1.7) | NS | PR 0.4 (0.0 to 3.9) | NS |
| >17.5 mg/week | de Thurah et al27* | 65 | Non-adherence (CQR ≤25th centile) at 9 mo | PR 1.0 (0.4 to 2.4) | NS | PR 1.1 (0.4 to 3.1) | NS |
| Other sDMARDs | |||||||
| MTX + HCQ vs MTX | Grijalva et al23 | NP | Adherence (MPR) | β 0.13 (0.14 to 0.11) | NP | β 0.11 (0.13 to 0.09) | <0.001 |
| MTX + HCQ vs MTX | Contreras-Yanez et al24† | 93 | ≥80% adherent (7-day DRR) | OR 3.9 (0.64 to 23.05) | 0.14 | NP | NP |
| MTX + HCQ + SSZ + LEF vs MTX | Contreras-Yanez et al24† | 70 | ≥80% adherent (7-day DRR) | OR 21 (1.5 to 293) | 0.02 | NP | NP |
| MTX + HCQ + SSZ vs MTX | Contreras-Yanez et al24† | 70 | ≥80% adherent (7-day DRR) | OR 3.7 (0.68 to 20.2) | 0.13 | NP | NP |
| MTX + SSZ vs MTX | Contreras-Yanez et al24† | 70 | ≥80% adherent (7-day DRR) | OR 5.3 (0.49 to 56.8) | 0.17 | NP | NP |
| Other bDMARDs | |||||||
| MTX + INF vs MTX | Grijalva et al23 | NP | Adherence (MPR) | β 0.12 (0.07 to 0.18) | NP | β 0.12 (0.07 to 0.17) | <0.001 |
| MTX + ETA vs MTX | Grijalva et al23 | NP | Adherence (MPR) | β 0.12 (0.09 to 0.15) | NP | β 0.11 (0.08 to 0.14) | <0.001 |
| MTX + ADA vs MTX | Grijalva et al23 | NP | Adherence (MPR) | β 0.06 (0.02 to 0.10) | NP | β 0.07 (0.03 to 0.11) | 0.001 |
| Biological yes vs no | Waimann et al30 | 107 | Per cent of adherence (MEMS) | 63±21 vs 66±17 | NS | NP | NP |
| Salt and Frazier29† | 108 | Non-adherent (MARS ≤38) | NP | NP | OR 1.26 (0.63 to 2.53) | 0.51 | |
| Drugs related to RA | |||||||
| Number of RA drugs | Contreras-Yanez et al24† | 93 | Adherent (CQ ≥9) vs non-adherent (CQ ≤8) | 4.8±1.5 vs 4.7±1.4 | 0.65 | NP | NP |
| Waimann et al30 | 107 | Per cent of adherence (MEMS) | r 0.05 | >0.20 | NP | NP | |
| Pills/day of RA drugs | Waimann et al30 | 107 | Per cent of adherence (MEMS) | r 0.08 | >0.20 | NP | NP |
| Drugs unrelated to RA | |||||||
| Number of drugs for comorbidity | Contreras-Yanez et al24† | 93 | Adherent (CQ ≥9) vs non-adherent (CQ ≤8) | 3.2±1.7 vs 3.2±1.9 | 0.94 | NP | NP |
| Number of non-RA drugs | Waimann et al30 | 107 | Per cent of adherence (MEMS) | r −0.17 | 0.07 | NP | NP |
| Pills/day of non-RA drugs | Waimann et al30 | 107 | Per cent of adherence (MEMS) | r −0.15 | 0.12 | NP | NP |
| Adverse events | de Klerk et al22†,‡ | 127 | Per cent of adherence (MEMS) | NP | NS | NP | NP |
| Folic acid use | de Thurah et al27* | 85 | Non-adherence (CQR ≤25th centile) at BL | PR 0.2 (0.0 to 1.6) | NS | PR 0.3 (0.0 to 2.7) | NS |
| de Thurah et al27* | 65 | Non-adherence (CQR ≤25th centile) at 9 mo | PR 0.6 (0.2 to 2.4) | NS | PR 0.4 (0.1 to 2.6) | NS | |
*MTX adherence.
†Studies judged low quality.
‡Includes RA, PMR and gout.
9 mo, 9 months; ADA, adalimumab; bDMARD, biological disease-modifying antirheumatic drug; BL, baseline; CQ, Compliance Questionnaire; CQR, Compliance Questionnaire—Rheumatology; DRR, drug record registry; ES, effect size; ETA, etanercept; HCQ, hydroxychloroquine; INF, infliximab; LEF, leflunomide; MARS, Medication Adherence Revised Scale; MEMS, Medicine Event Monitoring System; MPR, medication possession ratio; MTX, methotrexate; NP, not presented; NS, non-significant; PR, prevalence ratio; r, Pearson correlation coefficient; RA, rheumatoid arthritis; sDMARD, synthetic disease-modifying antirheumatic drug; Sig, significant; SSZ, sulfasalazine; β, regression coefficient.