AB0254 NEUROPSYCHIATRIC ADVERSE DRUG REACTIONS ASSOCIATED WITH LOW DOSE METHOTREXATE IN RHEUMATOID ARTHRITIS PATIENTS
Authors: J. Van Lint, T. Bakker, P. Ten Klooster, H. Vonkeman, N. Jessurun
Journal: Annals of the Rheumatic Diseases (2021)

Background: Neuropsychiatric adverse drug reactions (NPADRs) are well known with high dose methotrexate treatment. However, NPADRs have also been observed with low dose methotrexate (LDMTX) treatment in real world rheumatology data. Objectives: To evaluate the association between LDMTX and NPADRs, the impact of these NPADRs on further treatment and on health related quality of life (HRQoL) in patients with rheumatoid arthritis (RA) using real world data. Methods: The nature and frequency of NPADRs associated with LDMTX in the Dutch DREAM-RA registry were described. We assessed the causality of each NPADR with the Naranjo Probability Scale (NPS), the impact of NPADRs on further LDMTX treatment and the impact on patient reported HRQoL. NPADRs were structured using terminology of the Medical Dictionary for Regulatory Activities. Results: A total of 71 NPADRs (frequency 6.8%) associated with LDMTX were captured in the DREAM-RA registry. NPADRs were registered for 62 (5.9%) out of 1048 patients with 10.9 NPADRs per 1000 patient years (Table 1). The most frequently reported NPADRs were headache, dizziness and depression. The causality was considered probable for 67 NPADRs (94.4%) and definite for 1 NPADR (1.4%). The NPADRs led to LDMTX withdrawal in 34 cases (47.9%) and LDMTX was not restarted in 16 cases (47.1%). Median mental HRQoL was significantly decreased around the occurrence of the NPADR and remained significantly lower after the event. Median physical HRQoL was not significantly affected. Table 1. Baseline characteristics of DREAM-RA patients using methotrexate with at least one neuropsychiatric adverse drug reaction Characteristics N=62 N (%) Female sex 40 (64.5%) Age in years, mean (± SD), range 59.8 (± 13.1), 25 – 82 Rheumatoid factor Positive 43 (69.4%) Negative 13 (21.0%) Unknown 6 (9.7%) Anti-CCP, n (%) Positive 34 (54.8%) Negative 19 (30.7%) Unknown 9 (14.5%) Methotrexate dosage in mg/week, mean (± SD) 18.7 (± 5.9) Specific methotrexate dosage &lt; 15 mg / week 5 (7.0%) 15 mg/week 28 (39.4%) 20 mg/week 11 (15.5%) 25 mg/week 14 (19.7%) 30 mg/week 5 (7.0%) Unknown 8 (11.3%) Concomitant medication at moment of NPADR Folic acid 68 (95.8%) Prednisolone 20 (28.2%) Anti-CCP: anti cyclic citrullinated peptides, NPADR: neuropsychiatric adverse drug reaction, SD: Standard Deviation Conclusion: The association between NPADRs and LDMTX in RA patients was recognised by HCPs and frequently led to LDMTX withdrawal and a decrease in mental HRQoL. Many NPADRs scored ‘probable’ using the NPS. Knowledge on the nature, frequency and impact of these NPADRs will enhance attention towards potential NPADRs during LDMTX therapy allowing better risk assessment and communication to patients. Disclosure of Interests: Jette van Lint: None declared, Tom Bakker: None declared, Peter ten Klooster: None declared, Harald Vonkeman Consultant of: BMS, Celgene, Celltrion, Galapagos, Gilead, Janssen-Cilag, Lilly, Novartis, Pfizer, Sanofi-Genzyme, Grant/research support from: Abbvie, Naomi Jessurun: None declared