New Treatment For Lupus Brings Hope Goodnet

Targeted therapies offer ‘dream’ of lupus treatment free from steroids, immunosuppression Systemic lupus erythematosus is a clinically and immunologically heterogenous, systemic autoimmune disease characterized by inflammatory symptoms such as fever, fatigue, rashes and joint pains. The disease can affect any organ or system in the body, and it worsens or progresses over time. Uncontrolled inflammation causes organ damage, which leads to increased mortality. Daily struggles of living with SLE Patients with SLE can experience pain and fatigue daily, which makes life difficult.

Something people unfamiliar with the disease do not realize is that many of the symptoms that most affect people with lupus — such as brain fog, joint pain and fatigue — are not visible. The fatigue caused by lupus is much different from the standard, “Oh, I didn’t sleep well last night.” It is more like the fatigue you get with a bad case of the influenza, where you can barely get out of bed to make it to the bathroom and back.

It is not the kind of fatigue that you can just push through with sheer willpower. Approximately 55% of people with lupus report partial or complete loss of income due to inability to work, and 65% report chronic pain as the most difficult aspect of their disease. These numbers, and the experiences of those patients, reflect the overall impacts of SLE and traditional treatment approaches, suggesting there is ample room for more treatment options.

The science behind the pathophysiology, treatments The pathogenesis of SLE is mediated by the production of autoantibodies, proinflammatory cytokines and low complement levels, dysregulated B and T cells — all parts of the immune system that contribute to inflammation and tissue damage throughout the body. The earliest SLE therapies consisted primarily of corticosteroids, cyclophosphamide, hydroxychloroquine and other drugs used to nonspecifically suppress the immune system and thereby reduce inflammation and its associated symptoms.

Corticosteroids are still the primary treatment used to manage lupus at its worst, because they help to get inflammation rapidly under control. However, long-term use of high-dose corticosteroids and other traditional immunosuppressants used to treat SLE can have severe and long-term side effects, such as high risk for serious infections and irreversible organ damage. This means that despite their short-term efficacy to get disease symptoms under control, these medications pose serious risks to long-term health, and other treatment approaches are desperately needed.

This idea of moving beyond steroids can sometimes be difficult to communicate to patients, because corticosteroids offer such rapid relief of symptoms, and that is really what people with SLE notice — and care about — most of the time. However, they do not see the slow and progressive underlying damage that occurs with steroids over time. They cannot feel that impact until much later. A new path forward The treatment landscape for SLE was relatively the same for some 50 years.

This changed with the approval of a novel class of drugs that are now redefining possibilities for people with SLE — biologics. Biologics have granted unprecedented results in lupus treatment, and they have made remission possible for people living with the disease. Whereas patients previously had to live with lengthy periods of waxing and waning symptoms, with occasional bouts of relief induced by immunosuppressive drugs, biologics can now target specific components or pathways of the immune system to disrupt or halt pathogenic inflammatory cascades altogether.

This results in long-term reduction in symptoms and ultimately remission for some patients, with fewer side effects. It further reduces the disease burden by decreasing the use of corticosteroids. Still, only about one-third of patients show a complete response to certain biologic therapies, suggesting that what works well for some patients may not work for others. For the latter, different approaches are needed. Tailored treatment approaches For some patients, their lupus is driven by B cells and cytokines. For others, it may be dendritic cells or interferons.

For still others, it may progress from one pathway to another. This is why the ability to target each of these individual pathways is the key to personalizing treatment approaches for each patient and managing the disease pathophysiology at its core. However, as we harness each new mechanism of action, it is essential, too, to develop and use knowledge of those pathways to determine which one best addresses the pathophysiology of an individual’s SLE.

Because of the central role of autoantibodies in lupus, the first biologics used for lupus depleted B cells and reduced production of autoantibodies. Biologics have since been developed to bind to interferon receptors or to inhibit Janus kinases and cytokines. These new pathways have allowed for significant improvements and achievement of disease remission for some patients, but not all, supporting the assertion that different pathways and approaches must be used to tailor treatments for each person.

Leading experts in immunology with diverse capabilities have pioneered novel approaches with breakthrough potential for lupus treatment, such as the targeting of CD40/CD40L and other inflammatory cascades, which have shown promise in phase 3 clinical trials. This ligand/receptor signaling pathway holds unique promise in treating lupus because it acts on B cells, T cells and antigen-presenting cells, implicating it as a multi-pronged facilitator of lupus pathology. Ultimately, the goal should be to deliver patients with SLE a steroid-free regimen and durable drug-free remission.

Freedom from immunosuppressive drugs and the side effects of corticosteroids is a dream for many physicians and patients, and these novel treatment approaches such as biologics and cell therapies are getting closer to that point. Advancing personalized medicine, one pathway at a time Novel and targeted therapies such as biologics and cell therapy are poised to harness impactful immunological pathways in SLE pathophysiology to more fully address the individual needs of everybody living with this challenging disease.

Connecting scientific research with community leaders and organizations that have deep roots in underserved populations, drug developers are targeting immune cell pathways with the potential to break through the limitations of current therapies. They aim to deliver the novel treatments needed to put patients into drug-free remission to truly transform patient lives. Anca Askanase, MD, MPH Professor of medicine Director and founder Columbia Lupus Center Columbia University Irving Medical Center New York For more information: Anca Askanase, MD, MPH, can be reached at ada20@cumc.columbia.edu. References: Bragazzi NL, et al.

Expert Rev Mol Diagn. 2019;doi:10.1080/14737159.2019.1665511. Kaul A, et al. Nat Rev Dis Primers. 2016;doi:10.1038/nrdp.2016.39. Lupus Foundation of America. Lupus facts and statistics. 2023. Accessed August 17, 2023. https://www.lupus.org/resources/lupus-facts-and-statistics Felten R, et al. J Am Acad Dermatol. 2022;doi:10.1016/j.jaad.2020.04.150. Dubey AK, et al. J Pharmacol Pharmacother. 2011;doi:10.4103/0976-500X.85930. Fanouriakis A, Bertsias G. Lupus Sci Med. 2019;doi:10.1136/lupus-2018-000310. Dollear M. Where Do We Stand with Lupus Treatments? Lupus Society of Illinois. December 15, 2021. Accessed April 17, 2025. https://www.lupusil.org/where-do-we-stand-with-lupus-treatments/ Kundnani NR, et al. Pharmaceutics. 2024;doi:10.3390/pharmaceutics16091176. DelveInsight Business Research, LLP.

The Positive Topline Results From Phase III Study of UCB/Biogen’s Dapirolizumab Pegol Brings a Ray of Hope in Systemic Lupus Erythematosus Therapeutic Space. PR Newswire. October 7, 2024. Accessed May 7, 2025. https://www.prnewswire.com/news-releases/the-positive-topline-results-from-phase-iii-study-of-ucbbiogens-dapirolizumab-pegol-brings-a-ray-of-hope-in-systemic-lupus-erythematosus-therapeutic-space--delveinsight-302268558.html.

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