Single-Center Study Finds Rituximab Effective for Lupus

May 11, 2016

Rituximab might even be effective for forms of Lupus that resist standard treatments.

A retrospective, single-center study - the largest of its kind - finds evidence that rituximab is an effective treatment for severe systemic lupus erythematosus and for forms of the disease that resist standard treatments.

Researchers at University College London Hospital analyzed the cases of 115 patients treated with rituximab at the hospital between June 2000 and December 2013, offering a rare long-term follow-up of lupus patients treated with the drug.

Patients received two infusions of 1 gram of rituximab each, two weeks apart, the researchers wrote in Arthritis Care & Research. They also received methylprednisolone, antihistamines and cyclophosphamide. After B-cell depletion resulting from the ritixumab treatment, patients received the immunosuppressant hydroxychloroquine. If possible, their corticosteroid doses were reduced. Most patients received this rituximab treatment because of musculoskeletal, mucocutaneous or renal involvement, the researchers wrote. Outcomes were evaluated six months after the treatment.

The response rate to treatment was 70 percent, as defined by improvements in BILAG score, anti-dsDNA antibody levels and C3 levels. After a single rituximab cycle, 38.2 percent of patients (28.9 to 47.5 percent, 95% CI) saw their anti-dsDNA level drop by at least half or normalize. C3 levels increased at least 25 percent in at least 36.5 percent of patients after one rituximab cycle. Forty-three percent (33.7-52.3 percent) of patients had a complete response, 29 percent (20.5-37.5 percent) had a partial response and 28 percent (19.6 to 36.4 percent) had no response. Ninety-four percent (89.3-98.7) of patients were CD19+ lymphocyte-depleted after treatment. The mean number of rituximab cycles was 1.95, plus or minus 1.18, with 46 percent of patients undergoing only one cycle.[[{"type":"media","view_mode":"media_crop","fid":"42432","attributes":{"alt":"Lupus","class":"media-image media-image-right","id":"media_crop_7094073565464","media_crop_h":"0","media_crop_image_style":"-1","media_crop_instance":"4592","media_crop_rotate":"0","media_crop_scale_h":"0","media_crop_scale_w":"0","media_crop_w":"0","media_crop_x":"0","media_crop_y":"0","style":"height: 114px; width: 171px; border-width: 0px; border-style: solid; margin: 1px; float: right;","title":"©ibreakstock/Shutterstock.com","typeof":"foaf:Image"}}]]

There were few adverse events. In 224 rituximab infusions total, there were 13 severe infections, 13 hypersensitivity reactions and 13 mostly mild infusion-related reactions, as well as 23 "other" events. One patient experienced the reactivation of hepatitis B and another died of acute respiratory distress syndrome after cyclophosphamide infusion.

Two clinical trials, the EXPLORER trial and the LUNAR trial found improvements in anti-dsDNA antibodytrea levels, complement levels and B-cell depletion with rituximab, but did not find that the drug was superior to other treatments. Other studies suggest that when other treatments have failed, rituximab may have a better track record.  

"Rituximab is the biologic agent with the most extensive off-label use in the treatment of refractory SLE and observational studies," the researchers wrote. "Much published data seem to contradict the results from the two available randomized controlled trials, suggesting a possible role for this drug in the treatment of SLE patients."

References:

Aguiar R, Araújo C, Martins-Coelho G, Isenberg D. Use of rituximab in systemic lupus erythematosus: a single center experience over 14 years. Arthritis Care & Research 2016. doi:10.1002/acr.22921.

Merrill JT, Neuwelt CM, Wallace DJ, Shanahan JC, Latinis KM, Oates JC et al. Efficacy and safety of rituximab in moderately-to-severely active systemic lupus erythematosus: the randomized, double-blind, phase II/III systemic lupus erythematosus evaluation of rituximab trial. Arthritis Rheum 2010;62:222-33. doi: 10.1002/art.27233.

Rovin BH, Furie R, Latinis K, Looney RJ, Fervenza FC, Sanchez-Guerrero J, et al. Efficacy and safety of rituximab in patients with active proliferative lupus nephritis: the Lupus Nephritis Assessment with Rituximab study. Arthritis Rheum 2012;64:1215-1226. doi: 10.1002/art.34359.