Background Persistence with methotrexate (MTX) therapy is longer compared to other conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) in patients with rheumatoid arthritis (RA). The majority of patients with RA stop MTX due to inefficacy or adverse events. There is currently no robust evidence on the clinical and demographic factors that may predict MTX failure in patients with inflammatory polyarthritis (IP) and its subset RA.
Objectives To: i) examine patient-reported reasons for stopping MTX in patients with IP and ii) investigate which factors are associated with MTX failure.
Methods Subjects in this study were participants in the Norfolk Arthritis Register (NOAR), a Primary care based inception cohort of patients with early IP. All patients recruited to NOAR between 1 January 2000 and 31 December 2008 commencing MTX as their first DMARD within 3 months of their baseline visit with at least 1 follow-up visit were eligible for inclusion. Patients were followed from their time of recruitment to their last follow-up visit up to 18 March 2013.
Baseline and annual follow-up assessments are conducted by a research nurse and include age at symptom onset, gender, smoking status, 28-swollen and tender joint count, visual analogue score (VAS) well-being. Blood is taken at baseline for measurement of CRP, shared epitope status, rheumatoid factor (RF), and anti citrullinated protein antibodies (ACPA), DAS28-CRP based on the three-component was calculated.
Medication details including start and stop date of any DMARD are recorded at each follow-up visit. Patient-reported reasons for stopping DMARDs are categorised into i) adverse events, ii) remission, iii) inefficacy, or iv) other. Adding a second DMARD within 6 months after MTX commencement was labeled as MTX failure due to inefficacy.
Time to MTX failure was assessed by Kaplan-Meier analysis for the total failure group and for those who stopped MTX due to adverse events or inefficacy. Univariable Cox proportional hazards regression models were used to assess potential predictors of MTX failure.
Results 431 patients were eligible, and followed for 2035 patient-years. The majority were female (63%) with a median age at symptom onset of 58 (IQR: 48-68) years. Median disease activity at baseline was DAS-28 3.8 (IQR 3.0 – 4.8). At baseline 297 (69%) of the cohort fulfilled the 2010 ACR/EULAR criteria for RA. Over the total study period there were 146 (34%) MTX failures, the probability of patients remaining on MTX at 2 years was 0.79 (95% CI: 0.75 – 0.83). 19% failed due to an adverse event, 9% due to inefficacy, 3% for other reasons and 3% stopped MTX due to disease remission.
Smoking at baseline was not associated with early MTX failure (data not shown). RF or ACPA negativity was associated with early MTX failure for all reasons combined (HR: 1.88, 95% CI: 1.33 – 2.66; HR: 2.11, 95% CI: 1.42 – 3.13, respectively). RF or ACPA negativity was associated with early MTX failure due to adverse events but not inefficacy. Shared epitope homozygosity was associated with earlier MTX failure due to inefficacy but not adverse events (HR: 4.21, 95% CI: 1.29 – 13.66; HR: 0.48, 95% CI: 0.20 - 1.17, Table 1).
Conclusions Female gender, HAQ, CRP, VAS well-being, shared epitope homozygosity, RF and ACPA negativity were the only clinical/demographic features found to influence MTX persistence.
Disclosure of Interest None declared