MANCHESTER, U.K. – Although around half of patients with refractory systemic lupus erythematous (SLE) benefit from rituximab treatment at 6 months, there is a subgroup of patients that appears to do worse, according to research presented at the British Society for Rheumatology annual conference.
Data from the British Isles Lupus Assessment Group Biologic Registry (BILAG BR) showed that 58.75% of patients showed an improvement in disease activity measured using the BILAG 2004 Index System at 3 months and 48.75% showed improvement at 6 months.
Persistent disease, however, remained in 20% of patients at 3 and 6 months, and deteriorating disease occurred in 15% at 3 months and 22.5% at 6 months.
“A similar pattern was seen with the SLEDAI-2K response, although a higher percentage of patients seemed to improve with this measure,” said BILAG BR study coordinator Emily Sutton of the Centre for Musculoskeletal Research at the University of Manchester, England, where the registry is based.
Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) responses at 3 and 6 months showed around 70% of patients had improved at both time points, 16%-18% had persistent disease, and 11%-13% had worsening disease.
BILAG BR is a UK-based, multicenter, prospective, observational study of patients with SLE who are refractory to standard immunosuppressive therapy and are starting treatment with a biologic drug or a conventional, nonbiologic therapy.
The registry was set up in 2010 with the aim of recruiting 220 patients into the biologic cohort and 220 patients into the conventional, nonbiologic therapy cohort to enable monitoring of the real-world safety and effectiveness of biologics, compared with standard immunosuppressive therapies in the treatment of SLE.
Prior data on rituximab therapy in SLE were inconclusive, Dr. Sutton noted, with two clinical trials – EXPLORER (Arthritis Rheum. 2010;62:222-33) and LUNAR (Arthritis Rheum. 2012;64:1215-26) failing to hit their primary endpoints and show a clear benefit for rituximab.
Nevertheless, data from an open-label, single-center study of 50 patients treated with rituximab show that around 42% of patients achieved remission at 6 months (Arthritis Rheum. 2009;61:482-7).
The current analysis of BILAG BR data looked at the response to rituximab at 3 and 6 months in a total of 80 patients. Most (92.5%) of the study subjects were female, with a median age at diagnosis of 29.4 years and a median age at enrollment into the registry of 39.5 years. Approximately 60% were white, 13.7% were of South Asian descent, 13.7% of African ancestry, and the remainder was of mixed ethnicity.
The BILAG 2004 Index System scores disease activity across nine organ systems, and Dr. Sutton noted that all organ systems were involved at baseline, but the most common systems involved were the mucocutaneous (41% of patients), renal (35%), and musculoskeletal (31%) systems.
“When we looked at the disease activity at 6 months by BILAG organ system, there were a number of new flares in systems not previously involved,” Dr. Sutton reported.
“SLE patients demonstrated a variable response to rituximab, not just in the organ system involved, but also in the magnitude of response and the duration of remission,” she said.
“It is, therefore, essential that we work towards a position where we are able to select those patients who are most likely to respond well to treatment,” Dr. Sutton observed.
Patients continue to be enrolled into the registry, and future work will look at whether there are any factors predictive of a response to rituximab and try to stratify patients for B-cell depletion therapy, she added.
BILAG BR is supported by unconditional educational grants from Roche and GlaxoSmithKline. Dr. Sutton has received research funding from Roche and GlaxoSmithKline.
