New EULAR systemic sclerosis recommendations illuminate a ‘significantly changed’ field
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Key takeaways:
- Combination therapy is recommended as a first-line treatment for pulmonary arterial hypertension in SSc.
- Novel recommendations suggest biologic DMARDs for skin fibrosis and interstitial lung disease.
EULAR has released new recommendations on the treatment of systemic sclerosis, advancing new treatments and updated approaches to key manifestations such as skin and lung fibrosis.
“The field has significantly changed, and, according to various health systems, three drugs have been approved at least in some geographical areas,” Yannick Allanore, MD, PhD, of the department of rheumatology at Université Paris Cité, who convened the task force that formulated the new recommendations, told Healio. “In line with the progresses made in rheumatology, we have now recommended both synthetic and biologic DMARDs in SSc, which was not the case in 2017. Thanks to these achievements, the design of trials has been strongly improved.”
The recommendations are an update of those released in 2017. There are a total of 22 recommendations, up from 17 in the previous iteration, with seven considered “substantially new,” according to the authors. An updated research agenda aimed at guiding future studies could also provide a hint at advances to come.
“This has been a long journey,” Allanore said. “Throughout the process, all members were highly committed, but we must give a special thanks to the systematic literature review team that reviewed more than 12,500 abstracts, and also the two patient representatives who carried the voice of all patients.”
To learn more, Healio sat down with Allanore and first author Francesco Del Galdo, MD, PhD, of the Leeds Institute of Rheumatic and Musculoskeletal Medicine, in the United Kingdom.
Healio: What are the most important changes from the 2017 EULAR recommendations for SSc?
Del Galdo: The 2017 recommendations were built on literature up to the end of 2014. Thanks to the new randomized controlled trials conducted in the field since 2014, most following on the research agenda prioritized in 2017, there are several new recommendations:
- 1. Upfront combination therapy with dual intervention for patients diagnosed with pulmonary artery hypertension (PAH). PAH is a very severe complication of SSc that, untreated, leads to heart failure and death in a very short time. In 2017, there were already data available to recommend two major classes of drugs, but new evidence has indicated that if they are used together since diagnosis, dual therapy is more effective in reducing progression of disease.
- 2. Mycophenolate mofetil and rituximab (Rituxan, Genentech) are now recommended for the treatment of skin fibrosis in SSc. Neither of them were present in the 2017 update.
- 3. Mycophenolate, rituximab, nintedanib (Ofev, Boehringer Ingelheim) and tocilizumab (Actemra, Genentech) are recommended in a very detailed treatment algorithm for the management of interstitial lung disease, also known as lung fibrosis. None of these interventions were recommended in 2017.
Healio: Many new recommendations touch on interstitial lung disease and skin fibrosis. What are the main clinical takeaways there?
Allanore: For skin, we have a standard of care that is based on synthetic immunosuppressants, which are mostly mycophenolate mofetil or methotrexate. If the patient is progressing on skin or lung in parallel, a step-up strategy is offered, with either an anti-fibrotic or biological immunosuppressants to be added, based on the global assessment of the disease, disease duration, background inflammation and the profile of interstitial lung disease.
Therefore, the trend is undoubtedly toward combination therapies, with the best example coming from the SENSCIS trial and the results obtained in SSc-interstitial lung disease for patients receiving mycophenolate plus nintedanib.
Healio: The new recommendations advocate against the use of anticoagulants in SSc-PAH, particularly warfarin. Why is warfarin singled out?
Del Galdo: Data from two independent trials have indicated that the use of warfarin — common in other forms of PAH — was associated with severe complications, including death, in patients with SSc. Although this was not the main objective of those trials, this observation warranted the experts to formulate a negative recommendation for the use of warfarin.
Healio: What are key elements of the proposed research agenda going forward?
Allanore: Priorities in the research agenda include evaluating the efficacy of immune suppression in the vascular and gastrointestinal manifestations of SSc, because data are lacking there, as well as going more in depth on the cardiovascular effects of biologic interventions, because this is a major area for survival of SSc patients.
Within musculoskeletal manifestations, calcinosis is a major concern with a significant prevalence — about 20% — and no drug having shown any effect until now. Another priority is to continue to expand the immune interventions and antifibrotic armamentarium with the goal to further build synergistic combinations and improve clinical outcomes in SSc.
Furthermore, we highlight that there might exist in SSc a vascular endotype in which several organs or tissues may be suffering from insufficient vascularisation. This had previously been identified according to the aggregation of some vascular damages, but we add to this concept that similar vasoactive drugs are used in different vascular conditions in SSc.
This is opening the door to more work to look for shared risk factors, similar pathogenesis, composite vascular endpoints and, ultimately, global vascular management with a drug regimen providing disease-modifying actions.
References:
Del Galdo F, et al. Ann Rheum Dis. 2024;doi:10.1136/ard-2024-226430.
For more information:
Yannick Allanore, MD, PhD, can be reached at yannick.allanore@aphp.fr; X (Twitter): @allanore.
Francesco Del Galdo, MD, PhD, can be reached at F.DelGaldo@leeds.ac.uk; X (Twitter): @delgaldoFrances.
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