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PHILADELPHIA -- Rituximab (Rituxan) matched IV cyclophosphamide for improving lung function in patients with interstitial lung disease (ILD) related to systemic sclerosis and other connective tissue diseases, and was associated with less toxicity, according to the RECITAL study.

With 101 patients randomized between the two drugs and treated for 20 weeks, both groups saw increases in forced vital capacity (FVC) of about 100 mL from baseline, reported Toby Maher, MB, MSc, PhD, of the University of Southern California in Los Angeles, and colleagues in . Maher presented select findings at the American College of Rheumatology (ACR) annual meeting.

The efficacy findings were somewhat disappointing, Maher explained, as the trial had aimed to show superiority for rituximab. But the rough equivalence was still a positive outcome, and the investigators were heartened to confirm that adverse events (AEs) were significantly less common with the biologic agent.

Rates of overall AEs were nearly 50% greater in patients assigned to cyclophosphamide (n=646 vs 445); much of the difference came in incidents involving the gastrointestinal and nervous systems, which were more than twice as common in the cyclophosphamide group. No class of events was substantially more common with rituximab.

Rituximab depletes B cells and is normally used in conditions marked by excessive activity in this cell population. A number of studies have indicated that B cells play some kind of role in connective tissue disease, and rituximab has been tried as a rescue therapy for ILD associated with these conditions. This has met with some success but until now the approach had not been tested in a randomized trial.

Patients in were randomized 1:1 to rituximab or IV cyclophosphamide in a double-dummy design. Infusions were given to both groups on the same schedule. Patients in the rituximab group received two infusions of the active drug, given on days 0 and 14, followed by placebo infusions through week 20. In the cyclophosphamide group, the drug was given every 4 weeks through week 20, plus a placebo dose on day 14 to match the rituximab group's schedule. Evaluations were conducted at weeks 24 and 48. After week 24, patients were permitted to receive other immunosuppressant agents as recommended by their clinicians.

The 101 patients included 44 with idiopathic inflammatory myositis (IIM), 37 with systemic sclerosis, and 16 with mixed connective tissue diseases (MCTD); Maher devoted his ACR presentation to results in each of these subgroups.

Patients with systemic sclerosis did not respond as well to either drug, with no significant improvement in FVC or other markers of lung function. FVC values fluctuated during the treatment phase in these patients, and were actually slightly worse than at baseline at week 24. FVC had returned essentially to baseline by week 48. In the MCTD groups, both drugs were effective, raising FVC by about 200 mL from baseline. Cyclophosphamide appeared slightly more effective than rituximab for the IIM patients -- higher than baseline by about 350 mL versus 250 mL at week 24, and by roughly 400 mL versus 200 mL at week 48 -- though the differences did not reach statistical significance.

Overall, "rituximab should be considered as an alternative to cyclophosphamide" in these patients, Maher said.

In an accompanying Lancet Respiratory Medicine , Andreina Manfredi, MD, and Marco Sebastiani, MD, both of the University of Modena and Reggio Emilia in Italy, agreed, but with an important caution.

"[The] RECITAL trial confirms the efficacy of rituximab, previously suggested only by case series and uncontrolled studies, but many questions remain to be addressed, mainly regarding combination therapy with antifibrotic drugs or other immunosuppressants," they wrote. Manfredi and Sebastiani noted that rituximab's proper role in connective tissue diseases remains to be established, as does optimal dosing and the necessary duration of treatment.

"Further large and specifically designed studies are needed to answer all unresolved questions," they stated.