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Preliminary results of the prevention substudy

Background

DU are a heavy clinical burden in SSc, therefore their prevention is highly warranted. The objective of this OT was to determine the relative effectiveness and safety of the current off-label use of (i) sildenafil, (ii) bosentan, and (iii) the combination of sildenafil and bosentan compared to intravenous (i.v.) application of iloprost and conventional treatment with vasodilating agents such as calcium channel blockers (CCBs) or ACE inhibitors (ACEi) for the prevention of new DU in SSc patients.

Methods

This OT (study ID HEALTH-F5-2012-305495-OT1) comprised two treatment arms, a prevention arm and a healing arm. The study protocol of the prevention arm has been published at ClinicalTrials.gov, identifier: NCT01836263.

Preliminary Results

A total of 1,394 patients were available for preliminary analysis and 1,210 of them were included in the prevention substudy. A history of DU was a significant risk factor for developing new DU (OR=3.146; 95%CI:1.19-8.31, p=0.021), therefore interim analysis was focused on secondary prevention (prevention of new DU in patients with a history of DU). 473 out of 1,210 patients had a history of DU and 268 of them had available follow-up data (58.2% limited and 41.8% diffuse SSc subset). 47 out of the 268 patients (17.5%) were on bosentan, 33 (12.3%) on sildenafil, 40 (14.9%) on iloprost, 31 (11.6%) on sildenafil and bosentan in combination and 117 (43.7%) on CCB/ACEi alone. In patients with a history of DU in the last 24 weeks, the treatment with CCB/ACEi when given alone was associated with a 7-fold increased risk of developing new DU compared to all other treatment arms  (OR=7.313, 95%CI: 1.248-42.85, p=0.027).

Preliminary Conclusion

A history of DU in the past 24 weeks should trigger an active prevention strategy. In this group, treatment with CCB/ACEi alone is associated with a 7-fold increased risk of developing new DU compared to all other treatment arms.

Outlook 

The patients who have been enrolled into the prevention substudy of OT1 until November 2015 will be followed up for 2 years until November 2017 as a EUSTAR clinical project under the auspices of EUSTAR and WSF. After completion of the OT1 prevention substudy, OT1 will facilitate the development of validated Delphi-guidelines regarding the optimal treatment for the prevention of DU in SSc patients.