Sjögren's drug pipeline prepares for 'next wave' after longtime lapse in therapies
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Novel therapeutic approaches and a robust drug pipeline may provide hope for patients with Sjögren’s syndrome, according to a presenter at the 2021 Congress of Clinical Rheumatology-East.
“We are at a pretty exciting time for systemic Sjögren’s,” Nancy L. Carteron, MD, associate clinical professor of rheumatology at the University of California, San Francisco, said in her presentation.
That said, she was realistic about the amount of work that needs to be done for researchers and clinicians interested in this condition. “The Sjögren’s field is behind lupus and RA with regard to understanding all the predisposing factors,” she said.
Understanding all of the factors and manifestations of the disease may help the research community beef up the pipeline and refine their approaches, Carteron noted.
Because Sjögren’s can take so long to develop and present clinically, early diagnosis and ongoing vigilance is important, according to Carteron. She added that clinicians should pay attention to both innate and adaptive immune parameters in managing the syndrome.
While the genetic factors that predispose an individual to Sjögren’s syndrome can vary by geography and ethnicity, she noted that the STAT4, IRF5, CXCR5, BLK, IL‐12A, TNIP1 and HLA‐DR3 pathways may be implicated.
“A lot of research is going on in understanding epithelial cells,” she added. Regarding autoantibodies, SSA (Ro), SSB (La), ANA (speckled), rheumatoid factor and muscarinic all may play a part in Sjögren’s syndrome
Patients with this syndrome can have “a whole range of manifestations,” with roughly half of patients experiencing arthritis, arthralgias, skin or gastrointestinal involvement, according to Carteron. Raynaud’s phenomenon is “not uncommon,” occurring in up to 30% of patients, while a similar proportion of patients may experience pulmonary complications like interstitial lung disease, pericarditis or peripheral or small fiber neuropathy.
Many of these complications are difficult to manage and can make a true diagnosis difficult for one important reason, according to Carteron. “They often do not occur at the same time,” she said.
Carteron spent a significant amount of time addressing the ocular and oral complications reported in patients with the syndrome.
“Vision‐threatening findings can be seen without symptoms,” she said, noting key symptoms of dry eye and corneal ulcers or corneal melt. “It is so important to have a good working relationship with an eye care professional.”
Regarding oral complications, Carteron noted that dry mouth can lead to a number of adverse outcomes, including rampant dental caries, chronic oral candidiasis, severe oral discomfort, taste alterations, mucosal atrophy and abnormal food digestion. She urged vigilance and referral to a dentist. “We can help prevent against the rampant dental damage that we still see in our patients,” she said.
Topical fluoride is strongly recommended for treatment of oral manifestations, along with lozenges or gum to stimulate salivary glands, pilocarpine or cevimeline. Calcium phosphate may be used as a remineralizing agent.
As for treatments for the broader systemic manifestations of Sjögren’s syndrome, Carteron highlighted the complicated story of rituximab (Rituxan, Genentech). “It has not panned out in formal clinical trials, so it is not formally approved” in the U.S., she said. However, both EULAR and the British Society for Rheumatology support is use. “Internationally, this is a mainstay.”
Inhibiting T cell activation with drugs like abatacept (Orencia, Bristol Myers Squibb) may be the “next wave” of Sjögren’s treatment, according to Carteron. However, further data on this approach are needed.
Looking deeper into the pipeline, Carteron noted that the janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway is “on the radar,” as is Bruton's tyrosine kinase (BTK) signaling.
Researchers are also investigating various cytokines, according to Carteron. “There is a lot of activity in this area,” she said.
As for hydroxychloroquine, Carteron offered a realistic perspective. “It is an old drug, but don’t throw it out of your toolbox yet,” she said.
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Carteron NL. Use of Biologics in the Treatment of Sjögren’s & Management of Fatigue & Inflammatory Musculoskeletal Pain in Sjögren’s. Presented at: Congress of Clinical Rheumatology-East annual symposium; August 12-15, 2021 (hybrid meeting).
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