I had the incredible opportunity to attend my first ACR Convergence in Washington, D.C., thanks to my friend and dedicated RA patient advocate, Eileen Davidson, the voice behind Chronic Eileen.
In a groundbreaking update, Sjogren's is now officially recognized as a disease, not just a syndrome, which acknowledges its seriousness, systemic nature, and profound impact on patients' quality of life.
Given this global recognition, I was captivated by two presentations that addressed the challenges in developing therapies for SjD and highlighted clinical trials with promising outcomes.
Challenges of disease-modifying therapy in Sjögren’s Disease
Dr. Alan Baer explored the fundamental tension between modifying Sjögren’s disease and providing symptom relief in clinical trial designs for Sjögren’s.
He emphasized the high morbidity and burden of Sjögren’s disease on patients, which includes not only Sicca symptoms like dry eyes, nose, mouth, and skin but also fatigue, morning stiffness, sleep disturbances, joint pain, brain fog, and other neurological manifestations.
What people with Sjögren’s disease want in a new systemic therapy
According to Dr. Baer, patients are not only looking for effective treatments but also therapies that address the following needs:
Improve management of daily symptoms such as fatigue, muscle and joint pain, dryness, neuropathy, and dysautonomia.
Reduce flare-ups.
Reduce the risk of long-term complications, including severe dryness and lymphoma.
Eliminate medications like prednisone and other long-term treatments.
He jokingly shared a fictional name for the ideal drug therapy for Sjogren's Disease: SjöGone (siccakinumab).
I've personally been waiting more than twenty years for pharmaceutical or biotech companies to develop a SjöGone!
Expectations of a modifying disease therapy in rheumatic diseases
Reduce disease activity
Improvement of physical function, quality of life, social and work capacity
Induce remission or low disease activity
Slow or stop the progression of the disease
Slow or stop damage
Sustained improvement over time
Overall, modify the natural course of the disease
What makes it challenging to create treatments that modify Sjögren’s Disease?
There is a weak correlation between disease activity, assessed by the ESSDAI (EULAR Sjögren's Syndrome Disease Activity Index), and the symptom burden assessed by the ESSPRI (EULAR Sjögren’s Syndrome Patient Reported Index).
By the time a patient is diagnosed, salivary gland dysfunction is often too advanced, making it potentially irreversible.
The progression of the disease is significantly slower than in other rheumatic conditions.
The scores used to measure disease activity do not fully capture Sjogren's systemic involvement. According to the ESSDAI, 15% of patients will develop severe systemic disease, yet up to 50% might experience systemic manifestations and other autoimmune conditions over 10 to 20 years.
Limitations of completed clinical trials
Currently, clinical trials exclude seronegative patients or those with associated autoimmune diseases like RA or Lupus. Additionally, there is a significant placebo effect at play.
In some studies, even if there is a statistically significant response, it may not always align with the relief of symptoms, indicating that the biological effects do not always translate into clinical improvements.
Saliva and tear flow has not shown significant improvement.
Due to the slow progression of the disease, patients may require more time in trials for effects to manifest.
How to obtain better results from clinical trials
Better outcomes could be achieved with improved tools to exclude non-autoimmune causes of Sicca symptoms, tools to predict the evolution of Sjogren’s disease in patients with Sicca and/or anti-SSA positivity, and a deeper understanding of symptom etiology.
Dr. Baer is the Founder and Director of Jerome L Greene Sjogren’s Disease Centre at Johns Hopkins University School of Medicine.
Clinical Trials in Sjögren’s Disease
Dr. George Bruyn provided an overview of the treatments trialled for Sjogren’s over the past 20 years and what’s in the pipeline.
As of now, there are no FDA-approved treatments for Sjögren’s Disease. This autoimmune disease is highly variable and challenging to treat due to its slow progression.
The silver lining is that over 20 clinical trials are underway for patients with Sjögren’s, with three trials reaching phase 3. This means these drugs will be tested on a larger group of patients.
The encouraging news is that pharmaceutical companies are increasingly prioritizing the development of treatments for autoimmune diseases.
My takeaway from this session is that at least one clinical trial shows early positive results and is advancing to phase three. Researchers are cautious about sharing these findings, as there have been instances in the past where drug clinical trials for Sjogren's failed during phase 2 or 3 trials.
Dr. George AW Bruyn is Senior Consultant Rheumatologist and Director of Rheumatology Clinics in Lelystad, the Netherlands.
Abstract: Nipocalimab shows promise for Sjögren's Disease patients
The abstract on Efficacy and Safety of Nipocalimab, an Anti-FcRn Monoclonal Antibody, in Primary Sjogren’s Disease: Results from a Phase 2, Multicenter, Randomized, Placebo-Controlled, Double-Blind Study (DAHLIAS) gained a lot of attention at #ACR24. Here is an overview of the study:
Study Background
Sjögren's Disease is a chronic autoimmune disorder marked by specific autoantibodies and infiltration of exocrine glands by lymphocytes. Nipocalimab, an anti-neonatal Fc receptor (FcRn) monoclonal antibody, reduces circulating immunoglobulin G (IgG) including autoantibodies by inhibiting IgG–FcRn interactions.
Overview
Participants: 163 adults with moderate-severe (primary)SjD, seropositive for anti-Ro60/-Ro52 IgG antibodies.
Method: Participants were given either 5 mg/kg or 15 mg/kg of Nipocalimab, or a placebo, every 2 weeks for 22 weeks.
Intervention: Patients were randomized to receive IV nipocalimab 5 mg/kg, 15 mg/kg, or placebo every 2 weeks until week 22, alongside standard care.
Primary Endpoint: Change from baseline in Clinical European League Against Rheumatism Sjögren’s Syndrome Disease Activity Index (clinESSDAI) score at week 24.
Safety Assessment: Up to week 30.
Results
Effectiveness: The 15 mg/kg dose of nipocalimab significantly improved disease symptoms compared to the placebo. The 5 mg/kg dose showed similar results to the placebo.
Safety: Adverse effects were similar across all groups. Serious side effects were rare and not clearly linked to the drug. The most common side effect was hypersensitivity reactions.
Improvements: Physician assessments and patient-reported outcomes improved in the 15 mg/kg group. Significant dose-dependent reductions in IgG and autoantibodies were observed.
Conclusions
Nipocalimab demonstrated significant efficacy in reducing disease activity in primary SjD at a 15 mg/kg dose and was well-tolerated.
The study supports the potential of FcRn inhibition as a therapeutic approach in SjD, highlighting the pathogenic role of IgG autoantibodies.
These findings indicate that nipocalimab could be a promising treatment for patients with moderate-to-severe SjD, warranting further investigation in larger clinical trials.
My thoughts as someone living with Sjögren's disease
ACR24 Convergence presented more research abstracts and scientific sessions focused on Sjögren’s than previous years. I couldn't even enter one session because it was overflowing with attendees. Luckily, I can watch the recording!
Clearly, there is growing interest in this neglected and difficult-to-treat disease, which is a positive sign.
As a patient, I felt validated because we have been ignored for decades. Both presenters addressed the barriers and limitations to conducting clinical trials for individuals living with Sjögren’s Disease. Most importantly, they expressed what patients want from systemic treatments.
Although potential drugs like nipocalimab are showing promising results and the clinical trial is advancing to phase 3, I wonder if it will be applicable to all individuals with Sjögren's Disease. What I would like to see for myself and fellow patients:
Nipocalimab or other novel therapies continue to demonstrate a reduction of disease activity in a larger group of patients.
Access: If the drug receives FDA approval, there will be no delay in approvals outside the U.S
Advancing diagnostic criteria: Unlocking more pathogenic pathways in Sjögren’s will lead to more accurate and early diagnoses, helping patients get the care they need sooner.
Seronegative Sjogren's patients: Develop treatments for seronegative patients who often face neurological manifestations.
SjD and co-morbidities: Is there any hope for patients with a long-standing disease who are also living with other autoimmune diseases?
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