Rituximab may offer a new treatment option in patients with systemic sclerosis.
Systemic sclerosis is a serious disease of the connective tissues, where the tissue grows abnormally and triggers the immune system to attack itself (autoimmunity). This can cause hardening (fibrosis) and swelling of the skin, as well as joint pain, digestive problems and lung disease caused by fibrosis and scarring. It usually starts in people aged 30–50 years of age, and is slightly more common in women than men.
Rituximab is one of a class of drugs called the biologics that was developed for use in other autoimmune diseases, and which may be able to help reverse fibrosis in patients with systemic sclerosis. Rituximab targets B cells in the immune system, helping to restore the immune balance.
WHAT DID THE AUTHORS HOPE TO FIND?
The authors wanted to see whether rituximab was effective in treating skin and lung fibrosis in patients with systemic sclerosis.
WHO WAS STUDIED?
The study included 88 patients with systemic sclerosis who were enrolled in a large observational registry called EUSTAR. Of these, 63 patients were receiving rituximab according to the decision of their doctor, and 25 patients were in a control group and were treated with other drugs. Patients were included in the rituximab analysis if they had been diagnosed with systemic sclerosis, were treated with rituximab and had at least one return visit recorded. Patients were excluded if they had received a stem-cell transplant.
HOW WAS THE STUDY CONDUCTED?
This was a post-hoc, nested case-control observational study across 42 centres. This means that the analysis used data that had already been entered into a registry database. Patients in a registry are not randomised to receive any particular drug, but instead are simply observed and their data recorded. Nested case control means that the authors selected a group of cases or patients using the drug of interest (rituximab) and then compared their results to a group of control patients who were not using the drug at the same time.
The study analysed data in each group including age, gender and disease duration, and the presence of autoantibodies, as well as the degree of skin and lung fibrosis. Data were collected over 6 months.
WHAT WERE THE MAIN FINDINGS OF THE STUDY?
The study found that rituximab improved skin fibrosis by 24% and stabilised lung function in patients with systemic sclerosis. There were no serious side effects reported, although some patients were fatigued and some had infections while they were being treated.
ARE THESE FINDINGS NEW?
There have been previous open-label, uncontrolled studies which pointed to anti-fibrotic effects of rituximab, and there was also one small study published that showed skin and lung function improvement. While these studies provided important insights on the use of rituximab in systemic sclerosis, they were limited by the low number of patients and study centres, and the lack of a control group. This was therefore the first time that a larger patient population has been analysed in this way.
HOW RELIABLE ARE THE FINDINGS?
There are some potential limitations caused by the observational nature of the study, since patients in observational trials are not randomised to receive a certain medication, and both patients and doctors know which drugs they are taking, which means that it is not possible to draw definite conclusions on the efficacy of rituximab compared with placebo (dummy) treatment. The authors accounted for patient preference for medication by matching patients for major baseline factors that influence the treatment decision for skin and lung, including severity, disease duration and disease subtype. Another limitation of the study design is that some data had to be entered afterwards (retrospectively).
Immunosuppressive co-treatment was matched between rituximab patients and controls, but it is possible that the application of methylprednisolone in rituximab patients had an effect on the results, although this is unlikely with only one or two applications.
Finally, the assessment of skin fibrosis can be very different between different examiners, but the registry requires that the same person performs baseline and follow-up examinations at each study centre, and doctors are given regular training which helps to improve standardisation.
WHAT DO THE AUTHORS PLAN ON DOING WITH THIS INFORMATION?
These results should be confirmed in randomised clinical trials, and studies are ongoing in France and the USA. It is hoped that further investigation will confirm whether rituximab is a good treatment option in people with systemic sclerosis.
WHAT DOES THIS MEAN FOR ME?
At present, these results are too early to influence treatment recommendations for patients, but they do suggest that hope for a new treatment may be confirmed in future studies.
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Date summary prepared: June 2015
Summary based on research article published on:17 January 2014,
From: Jordan, S. et al. Effects and safety of rituximab in systemic sclerosis: an analysis from the European Scleroderma Trial and Research (EUSTAR) group. Ann Rheum Dis 2015;74:1188–94. doi:10.1136/ annrheumdis-2013-204522LaySummary Date prepared: July 2015
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