An investigational biologic that targets T cells in patients with systemic lupus erythematosus significantly lessened symptoms in a subset of patients who completed a 24-week randomized trial.
In the overall analysis, the drug – rigerimod (Lupuzor) – did not perform significantly better than did placebo. But a post hoc analysis of patients with a higher clinical disease score found better results, with a response rate of 84% vs. 46% who took placebo, Dr. Robert Zimmer and his colleagues reported in the November issue of the Annals of the Rheumatic Diseases (2013 [doi:10.1136/annrheumdis-2012-202460]).
The drug was well tolerated, with 40% of the treatment group experiencing at least one side effect, compared with 49% of the placebo group, wrote Dr. Zimmer, president and chief science officer of ImmuPharma, the French company that is developing rigerimod.
Rigerimod is a made from a small nuclear ribonucleoprotein. Studies suggest that it inhibits T-cell reactivity, thereby reducing proteinuria, vasculitis, and dermatitis. It also prevented the production of antibodies to DNA from a lupus-model mouse.
The phase II study comprised an intent-to-treat group 149 patients who had baseline total scores of 6 or more on the SLEDAI-2K (Systemic Lupus Erythematosus Disease Activity Index-2K). They were randomized to three arms: subcutaneous injections of 200 mcg rigerimod every 4 weeks (group 1), every 2 weeks (group 2), or placebo injections.
All patients were treated for 12 weeks and then followed for an additional 12 weeks.
Most (96%) were women; their mean age at enrollment was about 38 years. The mean disease duration was about 8 years. The mean SLEDAI-2K total score was 11, and the mean physician’s global assessment (PGA), slightly more than 1. More than 80% were taking corticosteroids; about half were taking concomitant antimalarials and a quarter, concomitant azathioprine. Less than 5% were taking methotrexate.
Responders were considered those who had a reduction of at least 4 points in their baseline SLEDAI-2K score, with no increase in the PGA score. Treatment failures were those who had a severe disease flare, needed a steroid increase of at least 80 mg prednisone equivalent, or received biologics. Patients could continue their existing, stable medication regimens during the study.
The dropout rate was 9% (13 patients) – 8% of group 1, 2% of group 2 and 16% of the placebo group.
By the end of the 12-week treatment period, the response rate was significantly better in group 1 than in the placebo group (53% vs. 36%). Response in group 2 was not significantly different from group 1(45%).
By the end of week 24, the response rate had increased similarly in the entire study population (group 1, 59%: group 2, 59%; placebo, 53%). These rates were not significantly different from one another.
The target group analysis was conducted after the study’s end. The investigators restricted this group to patients whose SLEDAI-2K clinical –not overall – score was at least 6. "Despite the fact that this population had not been defined at the beginning of the study, the changes in the inclusion criteria led us to carefully analyze this population [clinical SLEDAI score of 6 and above] as this population will be the phase III population," they noted.
At week 12 in this population, there were significantly more responders in group 1 than in the placebo group (62% vs. 39%). The difference between group 2 and placebo was not statistically significant.
By week 24, groups 1 and 2 had similar response rates (69% and 62%), but these were not significantly higher than placebo (56%), with p values of 0.11 for group 1 vs. placebo and 0.28 for group 2 vs. placebo.
The investigators did not break down response by symptom, but did say "The apparent clinical benefit observed f or patients who received 200 mcg Lupuzor every 4 weeks, compared with those who received placebo every 2 weeks, were mainly due to an improvement in articular and cutaneous symptoms (arthritis and rash) at week 12."
The incidence of adverse events was low and similar between the groups; 40% of patients in each active group experienced at least one, compared with 49% of patients in the placebo group. The most common were injection site reactions, which occurred in 6% of group 1, 10% of group 2, and 2% of the placebo group.
One patient died during the trial. The cause of death was pneumonia, which was not deemed related to the study drug. The investigators noted that this patient had been on immunosuppressant therapy before entering the trial. Two other patients also developed pneumonia. "Thus," the investigators said, "while there did not appear to be an increased incidence of serious infections with Lupuzor in this short study, longer-term studies are needed to further characterise the overall tolerability profile of Lupuzor."