Multiple sclerosis treatment with interferon beta may infrequently cause thrombotic microangiopathy, resulting in acute kidney injury. However, a newly published literature review finds that early identification of the complication and treatment with eculizumab may help prevent end-stage renal disease.
Multiple sclerosis (MS) is a prevalent inflammatory demyelinating disorder of the central nervous system, mostly affecting young adults. Immunosuppressive therapies play an important role in managing the condition. It is mainly used to manage relapsing–remitting MS (RRMS). However, managing progressive forms of the disease remains challenging.
First-generation injectable disease-modifying therapies like interferon beta (IFNβ) 1a or 1b and glatiramer acetate have been cornerstone treatments for RRMS. Despite the established efficacy and tolerability of IFNβ, recent reports have highlighted its potential long-term adverse effects on various organs, notably kidney injury. This literature review, published in the Journal of Clinical Medicine, evaluated its risk in MS patients and explored treatment approaches.
IFNβ Therapy Causes Acute Kidney Injury in Many Patients on Prolonged Therapy
Studies have increasingly associated prolonged IFNβ therapy with systemic adverse effects, including kidney-related complications such as hypertension and thrombotic microangiopathy (TMA). While the occurrence of TMA under IFNβ treatment has been documented, its pathophysiological mechanisms are thought to be multifaceted and have not been fully elucidated.
Proposed mechanisms include increased platelet activation, endothelial damage mediated by IFNβ, thromboxane receptor activation, and complement system activation. Notably, the incidence of IFNβ-related TMA is expected to rise with the growing number of MS patients undergoing long-term IFNβ therapy.
The presentation of IFNβ-related TMA varies widely, underscoring the need for heightened clinical awareness. Manifestations range from systemic symptoms, such as malaise and flu-like symptoms, to neurological symptoms and urinary abnormalities, often preceding the onset of TMA.
Prompt recognition of prodromal signs is crucial in facilitating early intervention and preventing severe complications associated with TMA. Patients with IFNβ-related TMA typically present with severe kidney involvement, often accompanied by malignant hypertension and neurological manifestations. Despite the discontinuation of IFNβ therapy, additional treatments such as plasma exchange, immunosuppressive drugs, or eculizumab may be required, especially in cases of severe acute kidney injury.
Notably, eculizumab has shown promise in mitigating renal failure progression in IFNβ-related TMA. Moreover, considering that TMA occurs only on prolonged IFNβ therapy, and kidney damage is preceded by prodromes, its early diagnosis is possible, and early initiation of eculizumab may be quite beneficial in such cases.
Genetic analysis has revealed a minority of patients with causative mutations associated with TMA development, suggesting that environmental factors such as IFNβ exposure may trigger complement hyperactivation and subsequent TMA. While the cornerstone of management remains IFNβ withdrawal, adjunctive therapies targeting complement activation may hold promise in improving outcomes for severe cases of IFNβ-related TMA.
The Bottom Line
In conclusion, IFNβ-related TMA represents a rare but serious complication of prolonged IFNβ therapy in MS patients with a high risk of renal failure or end-stage renal disease. Vigilant monitoring for early signs of kidney involvement is essential in guiding timely intervention and optimizing patient outcomes.
Source:
Allinovi, M., Mazzierli, T., Laudicina, S., Pastò, L., Portaccio, E., Amato, M. P., & Trivioli, G. (2024). Thrombotic Microangiopathy as a Life-Threatening Complication of Long-Term Interferon Beta therapy for Multiple Sclerosis: Clinical Phenotype and Response to Treatment—A Literature Review. Journal of Clinical Medicine, 13(6), 1598. https://doi.org/10.3390/jcm13061598
