Characteristics of rheumatoid arthritis with immunodeficiency-associated lymphoproliferative disorders to regress spontaneously by the withdrawal of methotrexate and their clinical course: A retrospective, multicenter, case-control study

Objective To investigate clinical characteristics and time course of lymphoproliferative disorders (LPDs) in rheumatoid arthritis (RA) patients after methotrexate (MTX) discontinuation, in those who achieved spontaneous regression (SR). Methods We retrospectively reviewed clinical data from RA patients with LPDs obtained from eight institutions between 2000 and 2017 and compared clinical and pathological findings between SR and non-SR groups. Results Among 232 RA patients with LPDs, 216 were treated with MTX at the onset of LPD and 144 (66.7%) achieved SR after MTX discontinuation. Higher MTX doses, high titers of anti-CCP antibodies (>13.5 U/mL), and lower LDH and soluble IL-2 receptor levels were associated with SR. Lymphocyte count was decreased at LPD onset and increased at 2 weeks after MTX discontinuation in the SR group. Epstein-Barr virus-positive mucocutaneous ulcer, reactive lymphoid hyperplasia and unclassifiable B-cell lymphoma, were more frequent in the SR than in the non-SR group. In multivariable analysis, diffuse large B-cell lymphomas was an independent predictive factor for non-SR. In the patients with SR, 73.9% achieved partial or complete regression as early as 2 weeks after MTX discontinuation. Conclusion SR and non-SR in RA patients with LPDs after MTX discontinuation were associated with certain clinical characteristics.

Automated summary

This study investigated the clinical characteristics and time course of lymphoproliferative disorders in rheumatoid arthritis patients after methotrexate discontinuation, with a focus on those who achieved spontaneous regression. Among the patients, higher MTX doses, certain antibody levels and blood markers were associated with spontaneous regression. Certain types of lymphoid disorders were more common in the spontaneous regression group. Overall, 73.9% of patients who achieved spontaneous regression showed improvement within 2 weeks of discontinuing MTX.