There are a few concerns regarding this definition of failure. According to the general definition, treatment failure is defined as no-response or limited efficacy, which includes initial lack of response, responsiveness over time, and inadequate response (Mittal et al. 2012). van der Kooij et al., In their analysis of methotrexate failure, classified patients who either did not achieve the DAS 2.4 or experienced adverse drug events and subsequently advanced to the next treatment step as ‘failures’. For each DMARD, these ‘failures’ were further categorized into three groups based on the reason for failure: (1) insufficient clinical response (DAS >2.4), (2) toxicity related to adverse events leading to DMARD discontinuation, and (3) other reasons (Van der Kooij et al.2007). The duration considered here was 2 years. However, recent recommendations from both the ACR and EULAR suggest that if there is no response or an inadequate response to treatment, it is time to consider the next line of therapy. The specific duration for defining treatment failure is still debated and the ACR recommendations are not entirely clear (Fraenkel et al. 2021).
In contrast, the EULAR 2020 guidelines retain their previous recommendation: “If there is no improvement within 3 months after the start of treatment or if the target has not been reached by 6 months, therapy should be adjusted (Smolen et al. 2020). The definition of ‘improvement’ in the recommendations is unclear, and the response criteria used for drug approval may not be clinically useful. A practical definition might involve an inadequate response or difficulty in escalating the DMARD, which could necessitate stopping, changing, or adding another DMARD. It is advisable to engage in shared decision-making with patients and consider additional factors such as comorbidities, age, and the potential implications of changing medications.
REFERENCES
1. Mittal N, Mittal R, Sharma A, Jose V, Wanchu A, Singh S. Treatment failure with disease-modifying antirheumatic drugs in rheumatoid arthritis patients. Singapore Med J. 2012 Aug;53(8):532–6.
2. Van der Kooij SM, de Vries-Bouwstra JK, Goekoop-Ruiterman YPM, van Zeben D, Kerstens PJSM, Gerards AH, et al. Limited efficacy of conventional DMARDs after initial methotrexate failure in patients with recent onset rheumatoid
arthritis treated according to the disease activity score. Ann Rheum Dis. 2007 Oct;66(10):1356–62.
3. Smolen JS, Landewé RBM, Bijlsma JWJ, Burmester GR, Dougados M, Kerschbaumer A, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2019 update. Ann Rheum Dis. 2020 Jun;79(6):685–99.