medwireNews: Rituximab and cyclophosphamide have similar overall efficacy in patients with connective tissue disease (CTD)-associated interstitial lung disease (ILD), but rituximab may be associated with fewer adverse events, suggest findings from a phase 2b trial.
Speaking at ACR Convergence 2022 in Philadelphia, Pennsylvania, USA, Toby Maher (University of Southern California, Los Angeles, USA) said that “interstitial lung disease is now the leading cause of death in patients with systemic sclerosis [and is] one of the leading causes of death in patients with myositis.”
He added that cyclophosphamide, which is frequently used to treat people with severe or rapidly progressive CTD-ILD, “brings with it many challenges,” as it is “often poorly tolerated [and] has issues including infertility and risk of bladder cancer.”
The RECITAL trial, which was published simultaneously in The Lancet Respiratory Medicine, included 97 patients from the UK with severe or progressive ILD related to idiopathic inflammatory myositis (45%), systemic sclerosis (SSc; 38%), or mixed CTD (16%). Participants were randomly assigned to receive rituximab 1000 mg at weeks 0 and 2, or six cycles of cyclophosphamide 600 mg/m² every 4 weeks. Maher noted that with the exception of corticosteroids, other immunosuppressants were discontinued until week 24, after which time they could be prescribed at the treating physician’s discretion.
The investigators found that lung function improved to a similar degree in both treatment groups. Specifically, the mean change in forced vital capacity (FVC) from baseline to week 24 was 97 mL in the rituximab group and 99 mL in the cyclophosphamide arm, translating into a nonsignificant between-group difference of 40 mL after adjustment for age, sex, baseline FVC, and diagnosis.
In addition, the majority of secondary endpoints – including 6-minute walk distance, quality of life assessments, and disease activity scores – were comparable in the rituximab and cyclophosphamide arms at weeks 24 and 48.
Maher and team also conducted a subgroup analysis, finding that “there are perhaps some important differences between the CTD subgroups, but nonetheless the drugs seem to be effective across all of them.” He said that both rituximab and cyclophosphamide “appear to stabilize FVC” over 48 weeks in patients with SSc-ILD, and led to improvements in FVC in patients with mixed CTD or myositis. He noted that rituximab, but not cyclophosphamide, improved modified Rodnan skin score in those with SSc-ILD.
The presenter said that “the one area where we did see a difference [between rituximab and cyclophosphamide] was in the number of adverse events.” Although all participants in both arms experienced at least one adverse event, there were fewer events overall in the rituximab arm (445 vs 646 in the cyclophosphamide group), as well as fewer cases of gastrointestinal disorders (71 vs 170), administration site reactions (52 vs 91), and nervous system disorders (35 vs 72).
“My take-home from this is that rituximab should be considered as an alternative to cyclophosphamide in patients with CTD-associated ILD,” concluded Maher.
Discussing the RECITAL findings in a comment accompanying the publication, Andreina Manfredi and Marco Sebastiani, both from University of Modena and Reggio Emilia in Italy, say that the trial “confirms the efficacy of rituximab [in this population], previously suggested only by case series and uncontrolled studies.”
They point out, however, that “many questions remain to be addressed,” such as the potential benefits of combination therapy including rituximab, and the optimal duration of treatment.
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