Aim: Identifying the predictors of responsiveness and adverse events in methotrexate (MTX) treated patients with rheumatoid arthritis (RA) has been the focus of most concern, but still without consistent consensus. Methods: PubMed and OVID EMBASE were searched to collect relevant studies that addressed correlations between gene polymorphisms and efficacy and/or toxicity in MTX-treated RA patients. Allelic, recessive, dominant and over-dominant model were applied. Results: A total of 68 studies were included. For associations with efficacy, AMPD1 34C>T polymorphism was related to responsiveness in dominant model (odds ratio [OR]: 1.77; 95% CI: 1.19-2.63) and over-dominant model (OR: 1.59; 95% CI: 1.04-2.45). ATIC T675C polymorphism had association with responsiveness in recessive model (OR: 2.54; 95% CI: 1.23-5.26). For associations with toxicity, polymorphisms in TYMS 1494 del6 and FPGS rs10106 were correlated to absenting overall adverse events in recessive model (OR: 0.68; 95% CI: 0.49-0.95) and dominant model (OR: 0.54; 95% CI: 0.35-0.83) respectively while MTHFR C677T was associated with presenting overall adverse events in allelic model (OR: 1.29; 95% CI: 1.02-1.63), recessive model (OR: 1.38; 95% CI: 1.00-1.89) and dominant model (OR: 1.41; 95% CI: 1.02-1.94). Conclusion: Polymorphisms in AMPD1 34C>T and ATIC T675C predict responsiveness. The absence of TYMS 1494 del6 and FPGS rs10106 and presence of MTHFR C677T predict adverse events in RA patients treated with MTX. Moreover, variations of the associations were found between Caucasians and non-Caucasians.
The aims of this study are to characterize the biological disease-modifying antirheumatic drug (bDMARD) usage patterns in real-life and examine the remission rate of rheumatoid arthritis (RA) patients receiving bDMARDs in routine clinical practice in China. Consenting RA patients (18 years) from 15 teaching hospitals and receiving marketed bDMARDs were included. In total, 802 patients (81.3 % women, 49.0 +/- 13.9 years) were included; 89.5 % were receiving a combination of bDMARDs and conventional synthetic DMARDs (csDMARDS), whereas 10.5 % were receiving bDMARD monotherapy. Etanercept (including EnbrelA (R) and local brand Yi Sai PuA (R) and QiangkeA (R)), tocilizumab, adalimumab, and infliximab were used by 66.6 %, 17.0 %, 7.5 %, and 6.6 % patients, respectively. Etanercept was used at a mean weekly dose of 38.2 +/- 15.6 mg for 25.5 +/- 47.0 weeks and tocilizumab at 94.5 +/- 21.9 mg for 4.7 +/- 7.5 weeks. Overall rate of remission was 12.6 %, 5.4 % , and 3.5 % based on DAS28, CDAI, and SDAI scores, respectively. Compared with patients receiving bDMARDs for < 3 months, those receiving bDMARDs for 3 months exhibited significantly lower DAS28 scores (p < 0.0001), and a significantly higher proportion of patients who received bDMARDs for 12 months achieved the treatment goal (remission or low disease activity, 62.5 % vs. 18.3 %, p < 0.0001). Patients receiving combination therapy with csDMARDs exhibited lower DAS28 scores than patients receiving bDMARD monotherapy (4.3 vs. 4.8, p = 0.011). This large-scale real-world study showed that bDMARD usage patterns in routine clinical practice in China were in accordance with international guidelines for RA management despite the short treatment duration. Longer duration of bDMARD usage and combination therapy showed a favored outcome of RA.