Multitarget Therapy With Rituximab Plus Mycophenolate Mofetil Versus Rituximab Monotherapy in Systemic...

To compare the effectiveness and safety of rituximab (RTX) plus mycophenolate mofetil (MMF) vs RTX monotherapy in patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD).

We performed a retrospective comparative analysis among adults with radiologically confirmed SSc-ILD treated with RTX monotherapy or RTX plus MMF (a multitarget approach [MTT]) as an RTX-based treatment strategy. The primary outcome was improvement in percent predicted forced vital capacity (FVC%) > 5 percentage points at the end of the second year (ΔFVC > +5). Secondary outcomes included longitudinal FVC trajectories over 3 years, skin involvement, and safety. Longitudinal analyses used linear mixed-effects models, with additional sensitivity analyses using inverse probability of treatment weighting.

Among 109 patients (MTT, n = 42; RTX, n = 67), baseline FVC% was lower in the MTT group (50.6 vs 61.0). At the end of 2 years, ΔFVC > +5 occurred in 69% of patients receiving MTT compared with 33% receiving RTX 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, whereas serious infections were uncommon in both groups.

In this real-world study, RTX plus MMF was associated with favorable longitudinal FVC% trajectories compared with RTX monotherapy in a nonrandomized cohort, despite greater baseline disease severity in the MTT group. These findings support prospective evaluation of MTT, particularly in high-risk patients.