Preliminary results of the healing substudy
Background
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 i.v. iloprost and conventional treatment with vasodilating agents such as calcium channel blockers (CCBs) or ACE inhibitors (ACEi) for the healing of 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
Thus far, longitudinal data for 156 out of 265 patients with DU could be collected. 57% of patients were on vasodilators (sildenafil, i.v. iloprost and CCB, alone or in combination), 5.8% were on a single vasoactive drug (bosentan) and 37.2% patients were on combination therapy. The mean number of DU per patient at the inclusion visit was comparable among the three treatment arms. At 12 and 24 months, the mean number of healed DU per patient was 1.5 and 1.8 fold higher in the vasodilator group compared to the vasoactive and combination groups (p<0.013 and p<0.018), respectively. No significant difference in the mean number of healed DU per patient was observed at 6 months. Initial exploratory analysis also suggested that the estimated mean time to healing of at least one DU was 9.71 ± 2.2 months in in the vasoactive arm, 8.7 ± 0.5 months in the vasodilator arm and 7.9 ± 0.6 in patients on combination therapy. Furthermore, when considered separately, patients on sildenafil (±CCB) showed the highest healing rate at 6 months follow-up, compared to other drug combinations.
Preliminary Conclusion
The combination treatment appears to result in a shorter time to healing. However, a longer follow-up extension and a correction for concurrent treatment and confounding factors are still in progress.
Outlook
The patients who have been enrolled into the healing 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 healing substudy, OT1 will facilitate the development of validated Delphi-guidelines regarding the optimal treatment for the healing of DU in SSc patients.