Updated recommendations on the management of systemic sclerosis are currently under final review by the European League Against Rheumatism (EULAR) Scleroderma Trials and Research Group (EUSTAR). These updates include 16 new/revised recommendations that build on previous iterations, explained Otylia Kowal-Bielecka, MD, of the Medical University of Bialystok, Poland, who discussed the highlights of the revised recommendations at the EULAR Congress.1
The new recommendations will cover several new treatment options, but they will not cover biologics in great detail because there are too few data known about their use in systemic sclerosis to warrant firm recommendations, she noted.
“We believe that these guidelines provide knowledge to the broad community of rheumatologists who do not always have time to review new developments in the published literature in depth and help them manage their patients with systemic sclerosis,” she said.
The first guidelines on the management of systemic sclerosis were published in 2009, and incorporated data through the end of 2006.2 Since then, more drugs have become available and further studies have been published on newer and older drugs, thus the need for a revised version, Kowal-Bielecka explained.
The guideline process is as follows: scleroderma experts from EUSTAR centers were asked to submit questions that could point to areas of necessary recommendations. Of the 170 questions proposed, 46 questions focused on 23 treatment categories were selected for a systematic review of the published literature through September 2014. More than 30 experts from Europe and the United States formed a task force that also included 2 patients with scleroderma and a clinical epidemiologist. The task force met in October 2014 and developed the final 16 recommendations.
Categories have not changed since the 2009 version: Raynaud phenomenon (RP), digital ulcers, pulmonary arterial hypertension (PAH), skin and lung disease, scleroderma renal crisis, and systemic sclerosis (SSc)-related gastrointestinal disease.
Treatment of PAH has undergone the most revision. A number of new drugs are now recommended, including tadalafil (Cialis), riociguat (Adempas), ambrisentan (Letairis), and macitentan (Opsumit), as well and intravenous prostacyclin analogues such as epoprostenol (Flolan).
Phosphodiesterase-5 (PDE5) inhibitors and fluoxetine (Prozac) have been added to the list of treatment options for SSc-RP; in the previous recommendations, only dihydropyridine calcium antagonists and intravenous iloprost (only after oral therapy) were recommended. Fluoxetine has weaker evidence but could be considered for SSc-RP attacks.
PDE5 inhibitors also listed as options for digital ulcers, in addition to the previously recommended options, include intravenous iloprost and the endothelin-receptor antagonist bosentan (Tracleer). Based on new level 1 data from 2 randomized clinical trials, bosentan is recommended to reduce the number of new digital ulcers, particularly in patients with multiple ulcers who have suboptimal responses to calcium-channel blockers, PDE5 inhibitors, and iloprost.
For the management of skin and lung disease, hematopoietic stem cell transplant is now an option—but only for carefully selected patients with progressive scleroderma who are at risk of developing organ failure. Other options include methotrexate for skin manifestations of early diffuse SSc and cyclophosphamide for interstitial lung disease.
The expert panel believes there is sufficient evidence supporting the immediate use of angiotensin-converting enzyme inhibitors for scleroderma renal crisis. Glucocorticoids are also recommended, but this recommendation is based on retrospective studies. Patients’ blood pressure and renal function should be monitored while on steroids, Kowal-Bielecka reminded listeners.
Recommendations for the management of SSc-related gastrointestinal disease have been reworded to include prokinetic drugs and the intermittent or rotating use of antibiotics.
Several biologics were considered potentially promising, but after a systematic review, the panel concluded that there was not enough evidence at present to support their inclusion as recommended agents. The expert panel has developed a list of promising agents to study in the future.
The updated recommendations for the management of systemic sclerosis will be published after review by the EUSTAR panel, possibly later in 2015.
- Kowal-Bielecka O, Fransen J, Avouac J, et al. Update of EULAR recommendation for the treatment of systemic sclerosis. Presented at: 16th Annual European Congress of Rheumatology; June 10-13, 2015; Rome, Italy. Abstract OP0061.
- Kowal-Bielecka O, Landewé R, Avouac J, et al. EULAR recommendations for the treatment of systemic sclerosis: a report from the EULAR Scleroderma Trials and Research Group. Ann Rheum Dis. 2009;68(5):620-628.