This is a plain English summary of an original research article. The views expressed are those of the author(s) and reviewer(s) at the time of publication.
People with systemic lupus erythematosus (or lupus) have a similar risk of serious infection whether their treatment is a newer biological therapy (rituximab and belimumab) or more traditional immunosuppressant (azathioprine and mycophenolate mofetil), research found.
Using data from more than 1,000 people with lupus, researchers found that medications used to control lupus symptoms all had a similar risk of serious infections. The risk was raised in people on higher doses of prednisolone (a steroid that reduces inflammation), those with multiple long-term conditions and those with low antibody levels (hypogammaglobulinaemia).
The findings suggest that lupus may be best managed by drugs other than steroids and that many people’s prednisolone doses may need to be reviewed.
People with lupus and their clinicians will be reassured by the finding that these more targeted treatments have a similar risk of serious infections. The information in this study could inform clinician and patient discussions about treatment.
For more information about lupus, visit the NHS website.
The issue: is infection risk the same for all lupus treatments?
Lupus is an autoimmune condition. This means that the body’s natural defence system (immune system) attacks healthy parts of the body. Symptoms include joint pain, rashes and tiredness. It is a long-term condition, but treatment can improve symptoms. Lupus UK estimates that about 1 in 1000 people in the UK have lupus.
Treatments for lupus work by dampening the immune response. These treatments, along with the condition itself, put people with lupus at higher risk of infections than others. Serious infections can lead to hospital admission and even death.
People with severe lupus may be given the steroid prednisolone on top of their usual medication to manage flare-ups. Newer treatments (biological therapies, such as rituximab and belimumab) are more targeted and block only some – not all – immune cells. They are often reserved for people whose condition cannot be managed with traditional immunosuppressants, but they still have potential side effects.
The researchers explored the risk of infection with different medications for lupus. They also looked at the impact of other health conditions on rates of serious infection.
What’s new?
The study was based on data from 1048 people added to a national lupus register between 2010 and 2021. They all had moderate to severe lupus. As expected for this condition, most (90%) were women (average age was 39 years). The 64 UK hospitals providing treatment gave information about serious infections (requiring intravenous antibiotics and hospital admission, or resulting in further illness or death) for 12 months after participants had started taking a new lupus treatment.
Most people (71%) were prescribed rituximab; 11% took belimumab and 17% took standard treatments (including azathioprine and mycophenolate mofetil). In those receiving prednisolone, the average dose in the study was 10mg.
The study found that within 12 months of starting therapy:
- the numbers of people who developed serious infections was similar for rituximab (8%), belimumab (4%) and standard treatments (7%)
- serious infections became twice as likely with doses of prednisolone higher than 10mg (compared with lower than 10mg).
Adding additional lupus medicines (combination therapy) did not increase the risk of serious infections.
People with low antibody levels (hypogammaglobulinaemia) were twice as likely as others to develop a serious infection. Those with multiple long-term conditions (particularly diabetes and high blood pressure) were almost 50% more likely to develop a serious infection than those without long-term conditions.
Why is this important?
The study showed that rituximab, belimumab and standard treatments all come with a similar risk of serious infections in adults with moderate to severe lupus. Having multiple long-term conditions, especially high blood pressure and diabetes, raised the risk of serious infection.
People taking higher doses of prednisolone (more than 10mg/day) were at greater risk of serious infections than those on lower doses. The British Society for Rheumatology guidelines recommend that steroids (such as prednisolone) be used at their lowest effective dose for lupus. The researchers question the use of steroids as a mainstay of treatment for people with lupus. In line with recent European guidelines, they suggest that other drugs should be prioritised.
What’s next?
The findings will reassure both clinicians and people with lupus about the safety of biological therapies (rituximab and belimumab).
The researchers suggest more regular reviews of prednisolone doses, and of antibody levels. People with lupus and other long-term conditions need to be closely monitored for signs of infection, they say.
You may be interested to read
This summary is based on: Rodziewicz M, Dyball S, and others. Early infection risk in patients with systemic lupus erythematosus treated with rituximab or belimumab from the British Isles Lupus Assessment Group Biologics Register (BILAG-BR): a prospective longitudinal study. The Lancet Rheumatology 2023; 5: E284 – E292.
A study from the US that showed similar results: Materne E, and others. Comparative risks of infection with belimumab versus oral immunosuppressants in patients with nonrenal systemic lupus erythematosus. Arthritis & Rheumatology 2023; epub ahead of print: 10.1002/art.42620.
If you’re interested in taking part in research about lupus, visit the Be Part of Research website.
Funding: This study was funded by the NIHR Manchester Biomedical Research Centre.
Conflicts of Interest: Several of the study authors have received funding from pharmaceutical companies. See paper for full details.
Disclaimer: Summaries on NIHR Evidence are not a substitute for professional medical advice. They provide information about research which is funded or supported by the NIHR. Please note that the views expressed are those of the author(s) and reviewer(s) at the time of publication. They do not necessarily reflect the views of the NHS, the NIHR or the Department of Health and Social Care.
