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Multi-target Therapy with Rituximab plus Mycophenolate Mofetil versus Rituximab Monotherapy in Systemic Sclerosis-Associated Interstitial Lung Disease

In brief

Rituximab-MMF combo boosts lung capacity in 69% vs 33% with rituximab alone

In a retrospective cohort of 109 systemic sclerosis-ILD patients, adding mycophenolate mofetil to rituximab led to a at least 5 point rise in predicted FVC in 69% of patients, compared with 33% on rituximab alone, despite worse baseline lung function. The benefit persisted over three years, though herpes zoster was more common; prospective trials are needed to confirm efficacy.

Journal
The Journal of rheumatology (Q1)
Published
15 August 2026
Study design
Prospective / inception cohort
Evidence level
Level 2, Moderate (CEBM 2b)
Authors
Rudra P Goswami, Vamshikrishna Patel Kotha, Manupati Surya
PMID
42603716
DOI
10.3899/jrheum.2026-0069

Why clinicians should know about it

  • Picked for Rheumatology (top studies of the week, 16 August 2026): Retrospective cohort, RTX+MMF improves FVC in SSc‑ILD

Abstract

OBJECTIVE: To compare the effectiveness and safety of rituximab (RTX) plus mycophenolate mofetil (MMF) versus RTX monotherapy in patients with SSc-ILD. METHODS: We performed a retrospective comparative analysis among adults with radiologically confirmed SSc-ILD treated with rituximab monotherapy or RTX + MMF (MTT) as rituximab-based treatment strategy. The primary outcome was improvement in percent-predicted forced vital capacity (FVC%) of more than 5 percentage points at the end of 2nd year (ΔFVC>+5). Secondary outcomes included longitudinal FVC trajectories over three years, skin involvement, and safety. Longitudinal analyses used linear mixed-effects models, with additional sensitivity analyses using inverse probability of treatment weighting. RESULTS: Among 109 patients (MTT n=42; RTX n=67), baseline FVC% was lower in MTT group (50.6 vs 61.0). At the end of two years ΔFVC>+5 occurred in 69% of patients receiving MTT compared with 33% receiving rituximab alone. Over 3 years, the adjusted mean increase in FVC% was greater in the MTT group than in the monotherapy group (+12.9% vs +4.4%) with early separation of lung-function trajectories that was sustained throughout follow-up. The association between MTT and greater FVC improvement remained consistent across prespecified subgroups, including patients with severe baseline restriction (FVC% <45%). Herpes zoster occurred more frequently in the MTT group, while serious infections were uncommon in both groups. CONCLUSION: In this real-world study, RTX plus MMF was associated with favourable longitudinal FVC% trajectories compared with RTX monotherapy in a non-randomised cohort, despite greater baseline disease severity in the MTT group. These findings support prospective evaluation of MTT particularly in high-risk patients.

Abstract as published, via PubMed.

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For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.