Rituximab Demonstrates Potential Efficacy in Treatment of Special Forms of RA

Recently, a study published in the International Journal of Rheumatic Diseases suggested the efficacy and safety of rituximab intervention in patients with special forms of rheumatoid arthritis (RA). These effects were observed in patients with RA further burdened by lymphoproliferative disorder (LPD), rheumatoid vasculitis, or extra-articular organ involvement.

The pathogenesis of RA is not yet completely understood; however, this chronic, systemic, autoimmune disease typically carries poor prognoses exacerbated by joint destruction, functional disability, and worsened quality of life in patients. It is known that B cells play a role in RA’s pathology, primarily in how they drive synovial inflammation through disease-specific autoantibody production—such as anti–cyclic citrullinated peptide (anti-CCP) autoantibodies.

RA Xray Concept | image credit: stockdevil -stocke.adobe.com

The nature of RA and the use of immunosuppressants in its management make patients more vulnerable to developing conditions like lymphoma, which, as the authors note, directly correlates with poorer disease prognosis. The same is true for those who develop rheumatoid vasculitis, which generally occurs in longstanding, seropositive, poorly controlled cases of RA. Furthermore, in cases where extra-articular organ involvement arises, treatments here are not always effective for a patient’s arthritis, which in turn can contribute to increased morbidity and mortality rates.

Currently, there is no effective treatment paradigm demonstrated to benefit patients with RA worsened by the presence of these comorbidities; however, rituximab has shown potential in the treatment of RA, lymphoma, and systemic vasculitis separately. Rituximab is a chimeric, monoclonal, anti-CD20 antibody that can deplete B cells—which contribute to rheumatoid factor (RF) secretion of proinflammatory cytokines. Therefore, to address this treatment lack, researchers set out to evaluate the efficacy and safety of rituximab in the holistic treatment of these patients.

Between April 2010 and June 2022, all patients with RA and LPD or vasculitis who were treated with rituximab were analyzed. Data were collected from patient charts and disease activity was measured from the Clinical Disease Activity Index (CDAI, where higher scores indicated more severe disease) and the Disease Activity Score for 28 Joints-Erythrocyte Sedimentation Rate (DAS28-ESR, where scores under 2.6 indicate remission, and scores of 2.6-3.1, 3.1-5.0, and 5.1 and above indicate low, moderate, and high activity).

A cohort of 13 patients was eligible for analysis. All patients were female with average ages at RA diagnosis and rituximab initiation of nearly 44 and just over 61 years, respectively. RF was detected in 100% of patients, while anti-CCP antibodies were detected in over 75% (10/13). At rituximab initiation, mean CDAI and DAS28-ESR were 16 and 4.7, respectively. Sixty-one percent (8/13) of patients were treated for RA complicated by LPD while the remaining 38.5% (5/13) were treated for RA complicated by rheumatoid vasculitis. Rituximab dosage was 375 mg/m²/week 4 times at treatment initiation, although some cases allowed for decreased dosing at times. Mean follow-up and drug continuation was 52 and 39 months.

At 12 months of treatment, CDAI scores significantly improved from 16 to 5.1 (P .006), as did DAR28-ESR from 4.7 to 2.7 (P < .001). A total of 77% of patients achieved low disease activity or remission scores at this time. The serum RF titer also significantly decreased from 96.6 IU/L at drug initiation to 32.5 IU/L at 12 months (P = .01). Additionally, those with rheumatoid vasculitis (who also developed extra-articular skin ulcers) saw improvements in their condition.

Over the 52-month follow-up period, only 5 adverse events were reported in 5 patients: 1 experienced an infusion reaction, 1 experienced a fungal infection in the lungs, and 3 experienced other infections such as a urinary tract infection. Among these 5 patients, 1 experienced a recurrence of their LPD.

Overall, the researchers’ study highlighted the potential safety and efficacy of rituximab in patients with RA burdened by LPD, rheumatoid vasculitis, and extra-articular organ involvement. In their concluding thoughts, the authors reemphasized the insufficient treatment strategies available in this patient population and urged for future studies to confirm their findings.

Reference

Takanashi S, Yasushi K, Shuntaro S. Effectivness and safety of rituximab in special types of rheumatoid arthritis. Int J Rheum Dis. 2023;26(11):2240-2247. doi:10.1111/1756-185X.14920