PHILADELPHIA — Within the first managed medical trial to check the 2 medicine, rituximab and cyclophosphamide have been equally efficient in enhancing lung operate in sufferers with interstitial lung illness (ILD) related to idiopathic inflammatory myositis and blended connective tissue illness (CTD). The findings additionally revealed some nuanced findings that would assist make clear which drug to make use of in particular sufferers.
“We really feel that rituximab is an affordable various to cyclophosphamide as a remedy in sufferers with these illnesses,” stated Toby Maher, MD, of the College of Southern California, Los Angeles, who introduced outcomes of an evaluation of three illness subgroups from the RECITAL (Rituximab versus Cyclophosphamide for the Therapy of Connective Tissue Illness Related Interstitial Lung Illness) examine on the annual assembly of the American Faculty of Rheumatology.
“We did not present it to be higher, so I believe you’ll be able to moderately select between the 2, however rituximab nearly actually has the benefit of being safer and higher tolerated than cyclophosphamide,” Maher stated in an interview. The findings have been printed concurrently in The Lancet Respiratory Drugs.
RECITAL is a section 2b, randomized, managed trial to check the speculation that intravenous rituximab can be superior to cyclophosphamide for ILD-associated CTD.
The examine included adults with three separate diagnoses: myositis (n = 44), blended CTD (n = 16), and systemic sclerosis (SSc; n = 37). The examine was finished in the UK when Maher was with Imperial Faculty London.
Sufferers within the rituximab group obtained 1,000 mg of IV remedy at baseline and a couple of weeks, then placebo remedy each Four weeks to week 20. Cyclophosphamide sufferers obtained 600 mg/m2 of physique floor space intravenously each Four weeks for six doses.
“Once we designed this examine there was restricted proof for any remedy for any illness related to ILD,” Maher stated. “However cyclophosphamide brings with it many challenges. It may be poorly tolerated and carries points like infertility and threat of bladder most cancers.”
Improved Lung Operate
Whereas the examine failed to fulfill its main endpoint — superiority of rituximab versus cyclophosphamide — it did present that each medicine led to enchancment in lung operate, measured by the speed of change in pressured very important capability (FVC), in addition to high quality of life measures, Maher stated.
“Total by week 48, we noticed a couple of 5% enchancment in FVC within the cyclophosphamide group and roughly a 4% enchancment in FVC from baseline within the rituximab group, suggesting that each medicine nearly actually had a constructive profit on this affected person group,” he stated.
However secondary outcomes various considerably throughout the completely different illness teams. Sufferers with SSc noticed a slight deterioration with cyclophosphamide within the modified Rodnan pores and skin rating at 24 weeks (1.6 ± 5.7 models) however an enchancment with rituximab (–3.4 ± 8.1 models).
“One space the place we did see a distinction was within the variety of hostile occasions,” Maher stated. “They have been fewer within the rituximab arm — particularly gastrointestinal problems [and] nausea, which we noticed fairly incessantly following cyclophosphamide. Additionally, that they had fewer complications, which we noticed fairly incessantly following cyclophosphamide.”
Rituximab sufferers additionally had fewer infusion reactions, however the variety of infections was related between the 2 remedy teams, he stated.
“The affected person group that responded finest to remedy was the myositis group,” Maher stated in his presentation. “Cyclophosphamide truly seems to be more practical than rituximab in enhancing their illness. By the tip of 48 weeks, the cyclophosphamide group truly gained about 400 mL in FVC, so a near 20% enchancment.”
The rituximab group had “a bit little bit of a drop-off” in efficacy from weeks 24 to 48, though the trial did not repeat dosing at 6 months, “which is what maybe one may do in medical apply,” he stated.
Oliver Distler, MD, chair of rheumatology on the College Hospital Zürich, raised questions on concurrent corticosteroid use in examine sufferers that will have brought on a “spillover” within the examine’s efficacy evaluation. However Maher famous that steroid use was balanced in all remedy arms. Sufferers within the cyclophosphamide arm averaged 42.9 mg of hydrocortisone day by day versus 37.6 mg day by day within the rituximab arm. That represents a 12.3% discount in steroid publicity for the latter.
Distler famous that the myositis inhabitants represented the majority of these examine sufferers on steroids. “So within the myositis subanalysis we do see a mix of high-dose steroid plus cyclophosphamide and rituximab.”
Maher disclosed relationships with Boehringer Ingelheim, Genentech, GlaxoSmithKline, Bristol-Myers Squibb, AstraZeneca, Trevi, CSL Behring, Pliant and Veracyte. Distler disclosed relationships with quite a few pharmaceutical firms.
This text initially appeared on MDedge.com, a part of the Medscape Skilled Community.