Presented By: Blake Warner, DDS, PhD, MPH, Xavier Mariette, A. Darise Farris, PhD and Jacques-Eric Gottenberg, PhD.
Perspective by: Teri Puhalsky, BSN, RN, CRNI
Epigenetic Links between Immune and Salivary Gland Dysfunction-Demystifying of Sjogren’s Syndrome
Presented by Blake Warner, DDS, PhD, MPH
Dr. Warner started his presentation with some background information on Sjogren’s.
His bullet points included; a systemic autoimmune disease causing dry mouth and eyes. Incidence in the U.S. 1-4 million affected, 9:1 female, >40 years old, unknown etiology. Beyond supportive care, there are no FDA-approved drugs to treat SjD and the quality-of-life measures remain reduced. The SjD model-environmental insult (viral, epigenetic) in a susceptible individual (genetic) with both hormone and immune (innate and adaptive) system alterations.
From Pathophysiology to Targeted Therapy in Sjogren’s Disease. Presented by Xavier Mariette
Mr. Mariette presented information regarding 1 IFN (interferon) seen in SjD, new data on the link between IL7 and type 2 IFN. IL7 and type 2 interferon drive T cells to interact with salivary gland cells. When abatacept was used to target T cells failed in two recent studies. He discussed another way to target IFN and T cells was to use HCQ and Lef which had promising study data. There is a phase II trial looking at anti-CD40 (infusion) monoclonal Ab with some promising data. Several studies are underway to look at BAFF and B cell pathophysiology in SjD. Data suggests that depletion of B cells in tissue is incomplete and there is an increase in serum BAFF after rituximab.
Mr. Mariette discussed a study he authored discussing the safety and efficacy of subcutaneous belimumab and IV rituximab combination. There were 4 arms placebo, belimumab/rituximab, belimumab monotherapy and rituximab monotherapy. At week 52, there was a numerically higher proportion of responders in the belimumab/rituximab group than in the placebo group and it was sustained to week 68. In contrast with placebo, belimumab and rituximab monotherapies, salivary gland biopsies from the belimumab/rituximab showed near complete CD20 + B-cell depletion at week 24.
He then presented data on Ianalumab, (VAY736, Novartis) an anti-BAFF-R monoclonal Ab (infusion) that combines B-cell depletion and BAFF/BAFF-R inhibition. The change from baseline over time up to week 24 revealed a statistically significant dose response relationship.
Another possible pathway is to target plasmablasts and plasma cells using drugs that work in multiple myeloma:
- Atacicept-inhibitor of BAFF and APRIL
- Bortezomib and other proteasome inhibitors
- Daratumumab-anti-CD38 Ab
- Anti-BCMA Ab
- Anti-BCMA/CD3 bispecific Ab
His thoughts for current and future therapies; Classification based on immunophenotype of disease has improved,
- Interferon type 1 or type 2
- T cells
- B cells
- Plasma cells
There are drugs dedicated to each of these pathways. The next steps are to get reliable biomarkers of each of the phenotypes and to design stratified trials based on the biomarkers with specific drugs.
Teri Puhalsky, BSN, RN, CRNI
Membership Development Chair Registered Nurse
Medstar Orthopaedic Institute
Brandywine, MD
Teri Puhalsky currently resides in Maryland, where she works as an infusion RN at Medstar Orthopaedic Institute. She studied nursing at Excelsior College School of Nursing and has been practicing rheumatology since 2011. Teri received the Outstanding Clinical Performance Award as an LPN, obtained her CRNI in 2012, and is a member of Sigma Theta Tau International PhiPi Chapter. She strives for positive patient outcomes and firmly believes that collaboration with the healthcare team is critical for chronic disease management. With a patient-focused and evidence-based nursing practice, she knows all patients can receive quality, safe, and effective care.