Rituximab, Cyclophosphamide Beneficial for Treating Connective Tissue Disease-Related ILD

Treatment with cyclophosphamide and rituximab is beneficial for interstitial lung disease (ILD) associated with idiopathic inflammatory myositis (IIM) and mixed connective tissue disease (MCTD) compared with systemic sclerosis (SSc), according to research findings presented at the American College of Rheumatology (ACR) Convergence 2022, held from November 10 to 14, in Philadelphia, Pennsylvania.

In the Rituximab versus Cyclophosphamide for the Treatment of Connective Tissue Disease Associated Interstitial Lung Disease (RECITAL; ClinicalTrials.gov Identifier: NCT01862926) trial, researchers assessed the efficacy of rituximab and cyclophosphamide as first-line therapy for patients with severe or progressive ILD associated with IIM, SSc, and MCTD.

The effect of rituximab and cyclophosphamide were analyzed by CTD subgroup. Patients with ILD were randomly assigned 1:1 to receive cyclophosphamide 600 mg/m² body surface area administered every 4 weeks for a total of 6 doses or rituximab 1 g administered at baseline and repeated at 2 weeks. A double dummy design was used to maintain blinding of patients and trial staff.

The primary outcome of the subanalysis was rate of change in forced vital capacity (FVC) at 24 weeks. Secondary outcomes included FVC change at 48 weeks, safety and tolerability, patient-reported quality of life, and modified Rodnan skin score in patients with SSc.

The study cohort included 101 patients (51 in the rituximab group and 50 in the cyclophosphamide group). A total of 44 patients (45.4%) had IIM; 37 (38.1%) had SSc; and 16 (16.5%) had MCTD. Patients with MCTD and SSc vs those with IIM had greater ILD severity at baseline.

In the IIM group, both rituximab (241 mL; 95% CI, 92.9-388.2 mL) and cyclophosphamide (345.7 mL; 95% CI, 198.1-493.2 mL) resulted in significant improvements in FVC at 24 weeks. In the MCTD group, the changes from baseline were 208.0 mL (95% CI, 3.3-412.7 mL) with rituximab and 164.8 mL (-5.0 to 379.9 mL) with cyclophosphamide. In the SSc group, treatment with rituximab and cyclophosphamide did not improve lung function. The FVC changes at 24 weeks were -26.0 mL (-186.8 to 134.6 mL) with rituximab and -3.3 mL (-154.8 to 148.2 mL) with cyclophosphamide. However, rituximab vs cyclophosphamide was associated with an improvement in Rodnan skin score in patients with SSc (1.6±5.7 vs -3.4±8.1 units, respectively; difference, -4.47 units [95% CI, -7.99 to -0.95 units]; P =.013).

Study authors concluded, “Cyclophosphamide and rituximab had the greatest magnitude of benefit in patients with IIM and MCTD associated ILD. In SSc-ILD, therapy [stabilized] but did not improve lung function. In patients [with SSc] rituximab but not cyclophosphamide improved skin thickness measured by [modified Rodnan skin score] at 24 weeks.”

Disclosure: Several study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.