The European League Against Rheumatism has released its first recommendations for the management of Sjögren’s syndrome with topical and systemic treatments.
Dr. Sara McCoy
First author Manuel Ramos-Casals, MD, PhD, of Hospital Clinic de Barcelona Institut Clinic de Medicina i Dermatologia and colleagues on the multinational, multispecialty EULAR Sjögren Syndrome Task Force Group said the EULAR recommendations “synthesize current thinking” of management for Sjögren’s syndrome, which is complicated by individualized treatment that does not address the systemic disease and for which therapeutic decisions are often made based on expert opinion and personal experience because of a lack of data.
“Sjögren’s syndrome is generally treated through symptom management,” noted Sara McCoy, MD, who is director of the University of Wisconsin Health Sjögren’s Syndrome Clinic and was not involved in the recommendations, which were published in Annals of the Rheumatic Diseases. “Although we have measures to address these symptoms, we do not have any approved therapy that ameliorates the driving cause.”
There is limited high-quality evidence for many of the therapies discussed in the recommendations: In total, 9 randomized controlled trials, 18 prospective studies, and 5 case-control studies were included as evidence in the recommendations, and many involved a small number of patients.
The first overarching recommendation says that patients with Sjögren’s syndrome should be managed at centers of expertise using a multidisciplinary approach, the authors wrote. Two other overarching recommendations focus on how to manage certain patient cases. In cases of dryness, first-line therapy should include topical therapies for symptomatic relief, while clinicians should consider systemic therapies for patients with active systemic disease. All three overarching recommendations had a high level of agreement among task force members.
The task force also offered 12 specific recommendations on disease management, which take an “algorithmic approach” to Sjögren’s syndrome management that is guided by the EULAR Sjögren’s Syndrome Disease Activity Index (ESSDAI), Dr. McCoy said in an interview.
“The EULAR recommendations structure a clear approach to treatment of Sjögren’s manifestations, ranging from oral and ocular sicca management, to treatment of uncommon but severe systemic involvement of Sjögren’s,” she said.
Before treating patients for oral dryness symptoms, clinicians should evaluate salivary function at baseline using unstimulated whole salivary flows. First-line therapeutic approaches for oral dryness can include nonpharmacologic stimulation in cases of mild salivary gland dysfunction, pharmacologic stimulation in cases of moderate dysfunction, and substitution of saliva in cases of severe dysfunction, the authors said.
Ocular dryness should be assessed using ocular staining score followed by ocular surface–disease index, and once identified, it can be managed with artificial tears and ocular gels or ointments as first-line therapy. Topical immunosuppressive-containing drops and autologous serum eye drops are options for more severe or refractory ocular dryness.
Patients who have fatigue or pain associated with Sjögren’s syndrome should have their fatigue or pain scored with the EULAR Sjögren’s Syndrome Patient Reported Index (ESSPRI), and any concomitant disease should also be evaluated. Clinicians should consider acetaminophen and NSAIDs for treatment of acute musculoskeletal pain and other pain-modifying agents, such as hydroxychloroquine in cases of articular pain, despite a lack of evidence showing its efficacy in trials.
For systemic disease, the task force advised matching treatment to the organ(s) involved and using the ESSDAI to evaluate disease severity., They said that “patients presenting with at least moderate activity in one clinical domain, or with a global moderate disease activity score” of 5 or higher can be considered for systemic therapy.
Although many clinicians use glucocorticoids (GCs) for managing Sjögren’s syndrome, there is no evidence of the treatment’s efficacy in systemic disease. The task force recommended using glucocorticoids such as methylprednisolone at the minimum dose and withdrawing use “as soon as possible” in patients with inactive disease. “Based on the potential development of chronic damage in patients with uncontrolled systemic disease, some patients may require long-term therapy with GCs, especially those with severe organ impairments,” Dr. Ramos-Casals and colleagues wrote. “In these patients, the addition of immunosuppressive agents as GC-sparing agents is justified, always weighing the potential benefits and risks.” Because of a lack of head-to-head studies of different immunosuppressive agents, the task force did not recommend one particular agent over another.
One recommendation that contained a high level of evidence was for the use of B-cell targeted therapies for patients with severe, refractory systemic disease. Efficacy of rituximab was mixed in studies totaling more than 400 patients, but generally showed a positive outcome in at least one of the following areas: global response, organ-specific response, ESSDAI reduction, and prednisone reduction. The task force recommended that rituximab “may be considered” in “patients with severe, refractory systemic disease” and may be best for those with symptoms linked to cryoglobulinemic-associated vasculitis, with the potential of using belimumab (Benlysta) as rescue therapy. While systemic organ-specific therapeutic approaches vary, the general rule should be to treat with GCs first, followed by immunosuppressive agents and biologics as second-line therapy in cases refractory to GCs, either sequentially or in combination, the authors said.
For patients with B-cell lymphoma, clinicians should use individualized treatment based on the World Health Organization 2016 histologic subtype and the stage of the disease. While some clinicians employ a “watchful waiting” approach to treating low-grade hematologic neoplasia, “the decision to treat low-grade lymphomas or not must be discussed in a multidisciplinary committee, taking into account the fact that they are linked to the disease activity and are the ultimate stage of autoimmune B-cell activation,” the authors wrote.
The task force also defined a number of future research agenda goals for Sjögren’s syndrome treatment management, including developing personalized therapeutic approaches, finding predictors of biological response to agents used in treatment, and identifying biomarkers of poor outcomes.
In addition, EULAR acknowledged some research gaps exist in the guidelines for particular symptoms of Sjögren’s syndrome, such as in the case of fatigue. “The EULAR recommendations mention the common association of fatigue with Sjögren’s syndrome, though acknowledge that fatigue is more commonly seen in the same demographic cohort as Sjögren’s,” Dr. McCoy said. “Aside from exercise, there remains little available to address this common and burdensome symptom amongst Sjögren’s patients. Overall, this is a pertinent gap in knowledge in our Sjögren’s patients.”
The Sjögren’s syndrome recommendations were funded by EULAR. Many task force members reported relationships with industry in the form of advisory board and speaker’s bureau memberships, consultancies, and grants. Dr. McCoy reported serving on a data monitoring committee for Bristol-Myers Squibb unrelated to the data in the EULAR recommendations.
SOURCE: Ramos-Casals M et al. Ann Rheum Dis. 2019 Oct 31. doi: 10.1136/annrheumdis-2019-216114