November 12, 2022
2 min read
Maher T. 0003. Rituximab versus cyclophosphamide for the treatment of connective tissue disease associated interstitial lung Disease (RECITAL): A sub-group analysis of a multi-centre randomised controlled trial. Presented at: ACR Convergence 2022; Nov. 11-14, 2022; Philadelphia (hybrid meeting).
Maher reports consulting fees from Abbvie, Agomab, Apellis, AstraZeneca, Bayer, Biogen Idec, Blade Therapeutics, Bristol Myers Squibb, Boehringer Ingelheim, Bridge Therapeutics, Carthronix, Chiesi, CohBar, BSL Behring, Daewoong, Daitchi, DevPro, Endeavor, Fibrogen, Galapagos, Galecto, GlaxoSmithKline, Insilico, IQVIA, Kinevent, Pliant, Pfizer, Puretech, Qureight, Redx, Remedy Cell, Respivant Sciences, Roche, Shinogi, Surrozen, Theravance, Three Lakes Partners, Trevi, UCB, United Therapeutics, Veracyte and Vicore; speaking fees from Boehringer Ingelheim, Roche and United Therapeutics; and research funding from AstraZeneca, GlaxoSmithKline and UCB.
PHILADELPHIA — Rituximab is comparable in terms of safety and efficacy to cyclophosphamide among patients with interstitial lung disease associated with connective tissue diseases, according to data presented at ACR Convergence 2022.
“Interstitial lung disease is now the leading cause of death in patients with systemic sclerosis,” Toby Maher, MD, of the University of Southern California, Los Angeles, told attendees. He added that it is also among the leading causes of mortality in patients with myositis.
In the retrospective RECITAL trial, Maher and colleagues compared rituximab (Rituxan, Genentech) to cyclophosphamide as first line therapy for patients with severe or progressive interstitial lung disease (ILD) associated with idiopathic inflammatory myositis (IIM), SSc or mixed connective tissue disease (MCTD). He described it as a “basket” trial due to the diverse patient population.
Although cyclophosphamide has been a mainstay of treatment in this patient population, the drug comes with “many challenges,” according to Maher. He noted poor tolerance, infertility and bladder cancer risks have been associated with cyclophosphamide therapy.
There is an increasing body of data showing that rituximab may be a viable option in this patient group, he added.
Previously reported results from RECITAL demonstrated an improvement in the primary endpoint of forced vital capacity (FVC) at 24 weeks for both drugs in a larger population. In the current presentation, Maher reported on a subgroup analysis for patients with connective tissue disease.
Eligible participants were randomly assigned in a 1:1 ratio to receive rituximab 1 g at baseline and repeated at 2 weeks, or cyclophosphamide 600mg/m2 body surface area administered every 4 weeks for a total of six doses.
Overall, 49 patients received at least one dose of rituximab while 48 received at least one dose of cyclophosphamide.
“Generally, study retention was good,” Maher said.
The first primary endpoint was FVC at week 24. After this time point, the treating clinician was free to manage patients with their drug of choice. Maher suggested that many clinicians used mycophenolate mofetil (MMF).
At 24 weeks, results for the full cohort showed that rituximab yielded a 4% improvement in FVC, compared with a 5% improvement for cyclophosphamide.
“[This suggests] that both drugs almost certainly had a benefit in this patient group,” Maher said.
“We did not see any superiority of rituximab compared to cyclophosphamide,” he added. “From this we can conclude that both drugs had an effect in this disease group.”
The study also included subgroup analyses in specific patient populations. Results in the SSc group showed “similar effects” in terms of FVC between rituximab and cyclophosphamide between 24 and 48 weeks, according to Maher.
A similar outcome was reported in the MCTD group.
In the myositis subgroup, cyclophosphamide was more effective over the long-term.
“By the end of 48 weeks, the cyclophosphamide group gained a 20% improvement in FVC,” Maher said.
Conversely, there was “a little drop-off” in efficacy of rituximab in FVC between 24 and 48 weeks, he added.
Safety data demonstrated slightly fewer adverse events in the rituximab arm.
“Actually, the number of infections was similar between groups,” Maher said
Despite these results, Maher drew positive conclusions from the study.
“We failed to show that rituximab was more effective than cyclophosphamide in CTD-ILD,” he said. “But we did show that rituximab was similar to cyclophosphamide in a whole range of patients.”
Both drugs clearly show efficacy “across diseases,” Maher added.
“My take home from this is that rituximab should be considered as an alternative to cyclophosphamide in patients with CTD-ILD,” he said.