EULAR: Immunosuppressants Only to Spare Steroid Use in Sjögren’s Syndrome
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Rheumatologists treating patients with systemic Sjögren’s syndrome should tailor their therapies to organ-specific severity, with immunosuppressants only being used as a glucocorticoid-sparing agent, with no evidence supporting one agent over another, according to EULAR recommendations published in the Annals of the Rheumatic Diseases.
“The therapeutic management of [Sjögren’s syndrome] has not changed substantially in recent decades and is still based on symptomatic treatment of sicca symptomatology and broad-spectrum immunosuppression for systemic disease, with insufficient information on the differential efficacy and safety of the therapeutic options available,” Manuel Ramos-Casals, MD, PhD, of the Hospital Clinic de Barcelona, and colleagues wrote. “Treatment decisions remain challenging in clinical practice, without a specific therapeutic target beyond the relief of symptoms as the most important goal. Therefore, there is growing interest in the proposal of clinical guidelines by national scientific societies.”
They added, “In 2010, the [EULAR] promoted and supported an international collaborative study (EULAR SS Task Force) aimed at developing disease-specific activity indexes in [Sjögren’s syndrome] (EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI) and EULAR Sjögren's syndrome disease activity index (ESSDAI) scores, which are now widely used both clinically and in research.”
Continuing this work, EULAR aimed to develop its first evidence- and consensus-based recommendations for Sjögren’s syndrome with topical and systemic medications. The recommendations task force included 77 specialists in rheumatology, internal medicine, oral health, ophthalmology, gynecology, dermatology and epidemiology, as well as statisticians, general practitioners, nurses and patients representatives from 30 countries across five continents. A steering committee included 13 rheumatologists, four internal medicine physicians, a primary care physician, an oral health specialist, an epidemiologist, one statistician, one health-professional representative and two patient representatives.
Following a systematic literature review and a presentation of proposals from the steering committee, the task force split into nine working groups with each introducing their own draft language for recommendations. Proposals from each group were discussed and refined. During a second face-to-face meeting, task force members used the Delphi method, and graded each prospective overarching principle and recommendation in terms of level of importance. Recommendations scored as “important” by more than 80% of the task force were accepted. The final overarching principles and recommendations were ultimate approved by the EULAR executive committee.
The task force ultimately approved three overarching principles and 12 recommendations. According to the overarching principles, rheumatologists should manage Sjögren’s syndrome at, or in close collaboration with, centers of expertise, using a multidisciplinary approach. In addition, the first-line treatment for dryness should involve topical therapies aimed at symptomatic relief. Lastly, systemic treatments may be considered for active systemic cases.
The 12 recommendations are:
- Baseline salivary gland function should be assessed prior to initiating any treatment for oral dryness;
- The preferred first-line approaches for oral dryness are nonpharmacological stimulations for mild dysfunction, pharmacological stimulation for moderate cases and saliva substitution for severe cases;
- Artificial tears and ocular gels or ointments can be used as first-line treatments for ocular dryness;
- Topical immunosuppressive-containing drops and autologous serum eye drops may be used to treat refractory or severe ocular dryness;
- Patients demonstrating fatigue or pain should be assessed for concomitant diseases, with severity scored using specific tools;
- Analgesics or other pain-modifying agents for musculoskeletal pain may be considered, with the physician balancing potential risks and benefits;
- Systemic disease treatment should be tailored to organ-specific severity based on ESSDAI definitions;
- Glucocorticoids should only be used for as long as necessary to control active systemic disease, at the minimum dose;
- Immunosuppressants should be mainly limited to use as glucocorticoids-sparing agents, with no evidence supporting one agent over another;
- Physicians may consider B-cell-targeting treatments in patients with severe, refractory systemic disease;
- As a general rule, systemic organ-specific treatments may follow the sequential, or combined, use of glucocorticoids, immunosuppressants and biologics; and
- B-cell lymphoma should be treated on an individual basis, taking into account histological subtype and disease stage.
“The [Task Force] is convinced that adhering to these recommendations, including shared decision-making, assessing disease activity regularly with the ESSDAI instrument, and applying the sequence of drugs as proposed, will improve overall outcomes in a clear majority of patients with [Sjögren’s syndrome],” they added. “New research information on treatment strategies, predictive markers and other aspects will soon become available and will probably require an update of the recommendations in coming years. Until then, we hope that the current recommendations will be broadly applied in clinical practice and/or serve as a template for national societies to develop local recommendations.” – by Jason Laday
Disclosure: Ramos-Casals reports consulting fees from Bristol-Myers Squibb and Gilead. Please see the study for all other authors’ relevant financial disclosures.
Perspective
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David A. McLain, MD, FACP, FACR
This is an excellent review of the current state of the art in Sjögren’s syndrome management. Specific recommendations are given for the treatment of the “Sjögren’s triplet” (dryness, fatigue, and pain) to the management of systemic, extraglandular disease. The task force recommends the use of the ESSDAI and the recommendations are often based on the level of the ESSDAI score. I doubt that many rheumatologists are calculating the ESSDAI at office visits.
Finally, the task force discussed why it has been difficult to show efficacy in double-blinded Sjögren’s trials, namely that 1) the wrong primary endpoint was chosen, and 2) the trials have been small. The two trials for lupus that finally showed efficacy (for belimumab) were 1000 patients each. The Sjögren’s trials have been no more than 50-60 patients in each arm.
Two recent randomized clinical trials that have shown efficacy in preliminary trials were the combination of hydroxychloroquine and leflunomide and a second trial with anti-CD40. I personally have used the combination of hydroxychloroquine and leflunomide many times with good results. Unlike the doses used in the preliminary trial, which were hydroxychloroquine 400 mg twice daily and leflunomide 20 mg per day, I have used hydroxychloroquine 200 mg per day and leflunomide 10 mg per day.
In the recent Sjögren’s syndrome newsletter, Herbert S. B. Baraf, MD, reported that there are 62 trials for Sjögren’s underway and registered with clinicaltrials.gov. Hopefully we will have more treatments available in the near future for this common syndrome.
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