Understanding Sjögren’s Syndrome: Current Treatments and the Road Ahead

Note: The first part of this post is based on insights from the document titled “Treatment of Sjögren’s syndrome: current therapy and future directions” by Robert I. Fox, Carla M. Fox, Jacques Eric Gottenberg, and Thomas Dörner, published in Rheumatology 2021. The original document can be accessed here.

Introduction

Sjögren’s Syndrome (SS) is a complex autoimmune disorder that primarily affects the body’s moisture-producing glands. Characterized by symptoms like severe fatigue, dryness, pain, and glandular swelling, SS has been a challenge for the medical community, both in terms of diagnosis and treatment. This post delves into the current therapeutic approaches and the promising future directions in SS treatment.

What is Sjögren’s Syndrome?

SS is not just about dry eyes and mouth. It encompasses a range of symptoms including diffuse pain, glandular swelling, and various systemic manifestations. The challenge in treating SS arises because many patients enrolled in clinical trials often don’t show extraglandular manifestations, making it hard to gauge the efficacy of potential treatments.

Current Treatment Landscape

While there is no one-size-fits-all treatment for SS, several drugs have shown potential benefits:

• Glucocorticoids: Beneficial in reducing glandular swelling.
• Hydroxychloroquine (HCQ): Known for its efficacy in treating Systemic Lupus Erythematosus (SLE), it has shown promise in alleviating SS symptoms like arthralgias and myalgias.
• Methotrexate (MTX): A pilot study revealed its potential in improving dry mouth and eye symptoms.
• Azathioprine (AZA): Primarily used for treating specific extraglandular manifestations.
• Leflunomide (LEF): Demonstrated modest benefits in early-stage SS.
• Mycophenolic acid: Noted for reducing hypergammaglobulinemia, a condition of increased gamma globulins in the blood.
• Cyclosporine A (CSA): Found to improve dry mouth symptoms.
• Rituximab: An extensively studied monoclonal antibody with variable findings.

The Challenge of Clinical Trials

One of the primary reasons for the limited success in SS treatment is the targeting of incorrect biologic pathways in clinical trials. For instance, the focus on the TNF-alpha pathway instead of the more pivotal IFN-alpha pathway has led to unsuccessful outcomes.

Looking Ahead: Introducing Remibrutinib, Ianalumab, and Iscalimab

In the quest for new treatments, three promising candidates have emerged: Remibrutinib, Ianalumab, and Iscalimab. Notably, all three of these innovative drugs have originated from the Novartis pipeline, underscoring Novartis’s unwavering commitment to advancing research and treatment in autoimmune and inflammatory conditions.

Novartis’s Commitment:

Novartis has consistently demonstrated its dedication to the field of autoimmune diseases, particularly in primary Sjögren’s syndrome. The emergence of Remibrutinib, Ianalumab, and Iscalimab from their research pipeline is a testament to their relentless pursuit of groundbreaking treatments that can transform patients’ lives. Their investment in this disease area is not only commendable but also offers hope to countless patients worldwide.

Remibrutinib:

A recent study titled “Remibrutinib (LOU064): A selective potent oral BTK inhibitor with promising clinical safety and pharmacodynamics in a randomized phase I trial” sheds light on this potential new treatment. Remibrutinib is a selective, covalent Bruton’s tyrosine kinase (BTK) inhibitor. The study investigated remibrutinib’s pharmacokinetics, pharmacodynamics, and safety, showing its potential use for diseases driven by mast cells, basophils, and B-cells, such as chronic spontaneous urticaria, allergic asthma, or even Sjögren’s syndrome. The publication describing the results of the Phase II clinical trial is coming, but in the meantime you can check out our poster at EULAR2023.

UPDATE 20231108: The paper describing the clinical trial has been published -> “Efficacy and safety of remibrutinib, a selective potent oral BTK inhibitor, in Sjögren’s syndrome: results from a randomised, double-blind, placebo-controlled phase 2 trial”

Ianalumab:

Ianalumab (VAY736) is a new biologic with dual modes of suppressing B cells. The phase 2 clinical trial Safety and efficacy of subcutaneous ianalumab (VAY736) in patients with primary Sjögren’s syndrome: a randomised, double-blind, placebo-controlled, phase 2b dose-finding trial highlighted its potential efficacy in treating Sjögren’s syndrome. The phase 2b dose-finding study assessed the safety and efficacy of different subcutaneous doses of ianalumab in patients with moderate to severe primary Sjögren’s syndrome. The results indicated a dose-related decrease in disease activity as measured by the EULAR Sjögren’s Syndrome Disease Activity Index (ESSDAI) at week 24. Ianalumab was well-tolerated and safe, with no significant increase in infections.

Iscalimab:

Iscalimab is a novel anti-CD40 monoclonal antibody that has shown potential in treating primary Sjögren’s syndrome. The proof-of-concept clinical study Assessment of the anti-CD40 antibody iscalimab in patients with primary Sjögren’s syndrome: a multicentre, randomised, double-blind, placebo-controlled, proof-of-concept study investigated the safety and preliminary efficacy of iscalimab in patients with primary Sjögren’s syndrome. The results indicated that intravenous treatment with iscalimab resulted in a significant reduction in ESSDAI score compared to placebo. Adverse events were similar between iscalimab treatment groups and placebo groups. This study suggests a role of CD40-CD154 interactions in primary Sjögren’s syndrome pathology and indicates the therapeutic potential for CD40 blockade in this disease.

Conclusion

With such findings, Remibrutinib, Ianalumab, and Iscalimab could be game-changers in the treatment landscape of autoimmune and inflammatory conditions. As research progresses, we might see them becoming standard treatment options in the near future.

Author Notes

In this post, I’ve provided a brief overview of the research I’ve been a part of at Novartis Biomedical Research. The information shared is derived from scientific studies that are publicly accessible and have been published in reputable journals. I welcome any feedback or comments you may have. For further inquiries or to get in touch, please visit my personal page.