Predicting rituximab responses in lupus remains challenging


Key clinical point: Only the presence of constitutional symptoms at baseline and having more than one anti–extractable nuclear antigen (anti-ENA) antibody were related to rituximab response.

Major finding: Having more than one anti-ENA antibody was related to a worse response to rituximab at 12 months.

Study details: A cross-sectional study of 121 patients with systemic lupus erythematosus treated with rituximab during 2000-2016.

Disclosures: Dr. Isenberg has used rituximab to treat patients with lupus for almost 20 years but reported having no other competing interests. Dr. Sánchez Pérez reported having no disclosures in relation to the study.

Source: Sánchez Pérez H and Isenberg D. Ann Rheum Dis. 2018;77(Suppl 2):177. EULAR 2018 Congress, Abstract OP0255.



– Despite some “encouraging signs” seen in a cross-sectional study, it remains difficult to determine whether a patient with systemic lupus erythematosus (SLE) will respond to off-label rituximab therapy, according to David Isenberg, MD.

The presence of constitutional symptoms, which includes fatigue, at baseline were associated with a favorable response to rituximab at 6 months (odds ratio, 7.35; P = .01). Conversely, having more than one anti–extractable nuclear antigen (anti-ENA) antibody was associated with a worse response to rituximab at 12 months (OR, 0.33; P = .032).

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“It’s not a cure for lupus, that’s obvious, but used at the appropriate time in the right sort of patients, it can be very helpful,” Dr. Isenberg said in an interview at the European Congress of Rheumatology. That’s both in terms of improving disease activity and reducing the use of glucocorticosteroids and immunosuppressive drugs, he noted.

“The great mystery, as with all drugs, is: Are there any markers which might tell us that the disease is going to do better with rituximab than perhaps with another form of medication, or is it just saying to us, ‘Whatever you do, it doesn’t make much difference’?” Dr. Isenberg said. He discussed the results of a study involving the first 121 patients treated with rituximab at his institution, University College London Hospital (UCLH); he noted this is one of the largest single-center cohorts of individuals with SLE who have used rituximab.

The aim of the study, which was presented at the congress by Hiurma Sánchez Pérez, MD, was therefore to try to find demographic, clinical, and serological markers that might help in predicting the response to rituximab in SLE patients.

Dr. Hiurma Sánchez Pérez, Hospital Universitario De Canarias, La Laguna, Tenerife, Spain, Sara Freeman/MDedge News

Dr. Hiurma Sánchez Pérez

Dr. Sánchez Pérez of the University Hospital of the Canary Islands, Tenerife, Spain, explained that data were collected for patients who were part of the UCLH cohort and treated with rituximab during 2000-2016. The treatment protocol used at UCLH initially consisted of 1,000 mg of intravenous rituximab given on days 1 and 15, with 750 mg of intravenous cyclophosphamide given on days 2 and 16. In 2004, the protocol was revised to include only one dose of cyclophosphamide. During rituximab treatment, all immunosuppressive drugs with the exception of hydroxychloroquine were stopped.

Response to treatment was determined using the British Isles Lupus Assessment Group (BILAG) Index. Patients who initially had markedly (BILAG A) or moderately (BILAG B) active disease but who no longer fell into these categories at 6 or 12 months were designated as responders. Those who remained were designated as nonresponders. In addition, any person moving into category A or B of the BILAG Index was said to have relapsed because of a flare in disease activity.

At 6 and 12 months, a respective 85% and 70% of patients exhibited a response to rituximab. Just under a quarter (24%) relapsed before 1 year, Dr. Sánchez Pérez reported.

Most of the patients in the cohort were white (n = 50) or Afro-Caribbean (n = 38), but ethnicity did not seem to play a role in predicting whether patients would respond to rituximab treatment.

Aside from constitutional symptoms and having more than one anti-ENA antibody, there were no other biological markers of response that remained significant after multivariate analysis.

The mean time to flare after rituximab was nearly 8 months, Dr. Sánchez Pérez said. Arthritis was the main manifestation seen during relapse (41% of patients), and mucocutaneous symptoms occurred in 21%. Biological markers of flare at 12 months after multivariate analysis were musculoskeletal symptoms at baseline (OR, 0.26; P = .039) and being anti-RNP antibody positive (OR, 10.56; P = .03).

“There were one or two encouraging signs,” said Dr. Isenberg, who was the senior author of the study. “Unfortunately, what I think the data show us, it remains pretty hard to know how any individual patient is going to respond to B-cell depletion using rituximab.”

Dr. Sánchez Pérez reported having no disclosures in relation to the study. Dr. Isenberg was one of the first people to use rituximab to treat patients with lupus but reported having no other competing interests.

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