RECITAL Trial: RTX vs. CTX in CTD-ILD Save

A UK study suggests the equivalent outcomes when patients with interstitial lung disease (ILD) associated with connective tissue disease (CTD) are treated with either intravenous rituximab (RTX) or cyclophosphamide (CTX), but with fewer adverse events with RTX. 

The RECITAL study was a randomised, double-blind, double-dummy, phase 2b trial to assess the superiority of RTX compared with CTX in adult CTD-ILD patients . whose ILD was deemed severe or progressive and related to scleroderma, idiopathic inflammatory myositis, or mixed CTD. Regimens included either IV rituximab (1000 mg at weeks 0 and 2 intravenously) or cyclophosphamide (600 mg/m2 body surface area every 4 weeks intravenously for six doses). The primary endpoint at 6 mos was rate of change in forced vital capacity (FVC). 

A total of 101 patients were randomized and 97 received at least one dose with 86% of CTX and 82% of RTX patients completing 24 weeks of treatment and follow-up.

At 24 weeks, FVC improvements were seen in both groups (CTX mean increase 99 mL; RTX increase 97 mL) with no significant differences (p=0·49) between the groups. Similarly, there were no significant differences in secondary endpoints between the treatment groups, with the exception of change in GDA score at week 48, which favoured cyclophosphamide (difference 0·90 [95% CI 0·11 to 1·68]).

There was less corticosteroid exposure (over 48 weeks) and fewer reported adverse events (445 vs 646 events) in the RTX patients. There were 5 deaths during the study (2 CTX; 3 RTX), all due to complications of CTD or ILD. Serious adverse events were equal between groups (33 CTX vs 29 RTX).

While this study showed that RTX was not superior to CTX in treating CTD-ILD patients, both treatments showed an increased FVC at 24 weeks, as well as clinically important improvements in quality of life. Thse data suggest that RTX is a reasonable therapeutic alternative to CTX in such patients. 

Abstracts reported at ACR 2022 looked at subanalyses related to CTD subset. Such results should be viewed with caution as the study was not powered to look at individual CTD subsets (eg, MCTD, myositis, scleroderma). These subanalyses of RECITAL showed: 

• Equal outcomes in MCTD ILD
• CTX was better than RTX in myositis related ILD.
• SSc-ILD shows both drugs stabilized but not improve FVC; but RTX (not CTX) improved skin thickness by mRss at 24 wks