Evolution of monoclonal gammopathy of undetermined significance in patients treated with JAK inhibitors for rheumatic diseases: data from the MAJIK-SFR registry.

OBJECTIVE: Monoclonal Gammopathy of Undetermined Significance (MGUS) is common but there are scarce data regarding the effect of disease-modifying antirheumatic drugs (DMARDs) on this pre-malignant condition. We aimed to evaluate the impact of JAK inhibitors (JAKi) on MGUS when initiated for an active rheumatic disease.

METHODS: Patients with monoclonal abnormality prior to JAKi initiation for an active rheumatic disease were identified through the MAJIK-SFR Registry, a french multicentre prospective study. Clinical and biological data were collected using a standardised case report form.

RESULTS: Twenty patients were identified with a mean age of 65 years and a diagnosis of rheumatoid arthritis (n = 15), psoriatic arthritis (n = 3), and axial spondyloarthritis (n = 2). The JAKi prescribed was baricitinib (n = 9), tofacitinib (n = 6) or upadacitinib (n = 5), with a mean duration of 15.5 months. Seventeen patients had individualized serum monoclonal protein (IgG Kappa n = 9; IgG Lambda n = 4; IgM Kappa n = 3; IgA Lambda n = 1) ranging from 0.16-2.3 g/dl, and three patients did not have initial measurable spike but a positive immunofixation. With a follow-up of 4-28 months, the serum monoclonal protein level decreased in 8 of 17 patients (47%), remained stable in 8 patients (47%) and increased in one patient (6%). The maximal decrease observed was an initial IgG Kappa of 2.3 g/dl decreasing to 0.2 g/dl at month 14.

CONCLUSION: This study brings reassuring and promising data on the MGUS evolution in patients treated with JAKi for rheumatic diseases, which may guide the choice of treatment in patients with both conditions.