Background Methotrexate (MTX) is an antimetabolite of folic acid commonly used for the treatment of Rheumatoid Arthritis (RA). Despite its recognized benefit in controlling the activity of the disease, it can cause side effects, such as hepatic and hematologic toxicity. This makes necessary to carry out periodic analytical controls.

According to the recommendations of ACR₁ and EULAR₂ on the monitoring of MTX toxicity, the most appropriate frequency for analytical controls in patients starting treatment with MTX would be 4-6 weeks, and it could be spaced up to every 3 months when reaching a stable dose.

We consider this study in view of the perception in our real clinical practice of a low frequency of analytical abnormalities that lead to modify the treatment with MTX in our patients with RA.

Objectives To evaluate the frequency of analytical abnormalities in patients with RA who start treatment with Methotrexate and to review the modifications in the treatments carried out based on these analytical abnormalities.

Methods Retrospective descriptive study on patients with RA who had started treatment with MTX (15 mg per week) between 2001 and 2021. The results of hematological parameters and liver function tests, obtained in the analytical controls carried out, were collected from the beginning of the treatment and during the following two years. These controls were carried out before starting MTX, one month later, at 3 months, and subsequently every 3-4 months; according to the recommendations of the clinical guidelines. The parameters collected were aspartate aminotransferase (AST), alanine aminotransferase (ALT), hemoglobin (Hb), neutrophils, and lymphocytes. Only patients treated with MTX in monotherapy, with or without corticosteroids, were included in the study. The frequency of the analytical abnormalities found was calculated and the therapeutic changes made were reviewed in the medical records.

Results 97 patients were included, of whom 67% were women and 33% men with a mean age of 55.94 (±12.9) years. Significant new-onset abnormalities in transaminases (>2-fold normal value: 68 U/L) were found in 8 patients (8.2%) during the 2-year monitoring. Of these, the MTX dose was modified in 6 patients (6.1%) and it was stopped in 2 patients (2.1%) due to ALT/AST>3-fold normal (102 U/L). After the suspension, the two patients normalized analytical values. Regarding the hematological parameters, anemia was observed (Hb <13 g/dl in men, <12 g/dl in women) in 10 patients (9.7%). However, none of them presented Hb < 10 g/dl and there was no treatment modification due to this alteration. Lymphopenia (lymphocytes < 0.9 x10^3/μL) was observed in 3 patients (3.1%) and neutropenia (neutrophils < 1.9 x10^3/μL) in 4 patients (4.1%). None of these patients required modifications in the treatment.

Conclusion The low incidence of analytical abnormalities found in our study makes us reconsider the frequency of analytical controls in monitoring MTX, not only to avoid unnecessary repeated venipuncture, but also the visits to health centers. On the other hand, we must not forget the cost of health and human resources that these procedures entail. Larger studies are required to elucidate the most optimal time interval required to monitor MTX toxicity in the management of patients with RA.

References

1. Guidelines for monitoring drug therapy in rheumatoid arthritis. American College of Rheumatology ad hoc committee on clinical guidelines. Arthritis Rheum, 39 (1996), pp. 723-731.
2. K. Visser et al. Multinational evidence-based recommendations for the use of methotrexate in rheumatic disorders with a focus on rheumatoid arthritis: Integrating systematic literature research and expert opinion of a broad international panel of rheumatologists in the 3E initiative. Ann Rheum Dis, 68 (2009), pp. 1086-1093.

Acknowledgements: NIL.

Disclosure of Interests None Declared.

Keywords: Rheumatoid arthritis, Disease-modifying drugs (DMARDs)

DOI: 10.1136/annrheumdis-2023-eular.2099