Risk factors for oral methotrexate failure in patients with inflammatory polyarthritis: results from a UK prospective cohort study

Abstract

BackgroundOral methotrexate (MTX) is the first-line therapy for patients with rheumatoid arthritis (RA). However, approximately one quarter of patients discontinue MTX within 12 months. MTX failure, defined as MTX cessation or the addition of another anti-rheumatic drug, is usually due adverse event(s) and/or inefficacy. The aims of this study were to evaluate the rate and predictors of oral MTX failure.MethodsSubjects were recruited from the Norfolk Arthritis Register (NOAR), a primary care-based inception cohort of patients with early inflammatory polyarthritis (IP). Subjects were eligible if they commenced MTX as their first DMARD and were recruited between 2000 and 2008. Patient-reported reasons for MTX failure were recorded and categorised as adverse event, inefficacy or other. The addition of a second DMARD during the study period was categorised as failure due to inefficacy. Cox proportional hazards regression models were used to assess potential predictors of MTX failure, accounting for competing risks.ResultsA total of 431 patients were eligible. The probability of patients remaining on MTX at 2 years was 82%. Competing risk analysis revealed that earlier MTX failure due to inefficacy was associated with rheumatoid factor (RF) positivity, younger age at symptom onset and higher baseline disease activity (DAS-28). MTX cessation due to an adverse event was less likely in the RF-positive cohort.ConclusionsRF-positive inflammatory polyarthritis patients who are younger with higher baseline disease activity have an increased risk of MTX failure due to inefficacy. Such patients may require combination therapy as a first-line treatment.Electronic supplementary materialThe online version of this article (10.1186/s13075-018-1544-9) contains supplementary material, which is available to authorized users.

Adherence with methotrexate in polish patients—Survey research results

“…People with longer history of illness and MTX treatment significantly more often give up further therapy, which is in concordance with previous results reported in the literature 6 . In Bluett et al observation in cohort recruited from Norfolk Arthritis Register of early inflammatory polyarthritis, 2 years of therapy continuation was observed in 82% of patients and 5 years in 72% 16 . In older studies percentage of patients continuing treatment after 2 and 5 years was much lower, respectively, 53% 17 and 45%‐57.1% 18,19 …”

The Clinical Value of Autoantibodies in Rheumatoid Arthritis

“…In the Utrecht RA cohort established in 1990, 36% of the patients achieved at least one period of remission; among other predictors, RF negativity was associated with 1.63 hazards of achieving remission (77). IgM RF positive patients were less likely to achieve remission also in other cohorts (78, 79), and a recent study on early RA patients commencing methotrexate (MTX) as their first disease modifying anti-rheumatic drug (DMARD) within 3 months of their baseline visit confirmed that RF was associated with earlier MTX failure due to inefficacy (80). In contrast, the predictive value of ACPA for achieving point remission is not that obvious.…”

From Rheumatoid Factor to Anti-Citrullinated Protein Antibodies and Anti-Carbamylated Protein Antibodies for Diagnosis and Prognosis Prediction in Patients with Rheumatoid Arthritis

“…Moreover, the presence of IgM RF in patient sera renders clinical remission less achievable. In fact, a recent study reported that RF is associated with early methotrexate (MTX) failure due to inefficacy in patients with early RA [ 136 ].…”