Objectives To evaluate the effect of methotrexate (MTX) withdrawal on disease activity and remission rate in patients at target after treatment with bDMARDs/tsDMARDs plus MTX. Methods We searched the PubMed, EMBASE, and CENTRAL databases for all RCTs on MTX withdrawal in patients with rheumatoid arthritis at target after combination therapy from inception to 2022–3-7 in order to extract data, including the change from withdrawal in DAS28 at the end point; proportion of low disease activity (LDA) assessed by DAS28, SDAI or CDAI; proportion of remission assessed by DAS28, SDAI, CDAI or ACR/EULAR Boolean remission. The Cochrane Q test and I2 test were used to assess heterogeneity, and random-effects models were used for data synthesis. This study is registered with PROSPERO (CRD42022303891). Results Six articles were included for qualitative and quantitative analysis, all of which were noninferior RCTs involving 1430 patients (734 in the withdrawal group and 696 in the continuation group). Compared with continuing combination therapy, tapering off or discontinuing MTX increased DAS28 by 0.20 (95% CI 0.09–0.32, I2 = 0%) and decreased the percentage of patients with LDA assessed by DAS28 to < 3.2 (RR 0.88 [0.80, 0.97] I2 = 0%). However, MTX withdrawal did not decrease remission rates assessed by DAS28, SDAI, CDAI or ACR/EULAR Boolean remission (RR 0.90 [0.81, 1.01], 0.93 [0.77, 1.11], 0.90 [0.74, 1.11], 0.95 [0.70, 1.29], respectively). Conclusion Withdrawing MTX slightly increases the RA disease activity in patients treated at target with bDMARDs/tsDMARDs plus MTX and has limited effects for patients with deep remission.

Multicentric reticulohistiocytosis (MRH) is a rare systemic disease of non-Langerhans cell histiocytosis. A number of studies in the literature have documented that it can coexist with malignancy or autoimmune disease, making it difficult to determine the most appropriate therapy. Here, we present a case study of MRH associated with posterior mediastinal adenosquamous carcinoma along with antinuclear antibody positivity and lupus anticoagulant positivity. The patient experienced 6 months of clinical benefit after surgical resection and chemoradiotherapy of the mediastinal malignancy. This case adds to the available literature on multicentric reticulohistiocytosis associated with different types of malignancy and provides supplementary clinical data on the coexistence of this syndrome with malignancy and immune system abnormalities. To the best of our knowledge, this is the first case study describing MRH accompanied by posterior mediastinal adenosquamous carcinoma and lupus anticoagulant positivity. The unknown aetiology and polymorphic clinical presentation of MRH warrants further investigation.