Standardised assessments of disease severity are important to facilitate patient management and follow therapeutic response in clinical trials. Recently, the Epidermolysis Bullosa Disease Activity and Scarring Index (EBDASI) was introduced as a valid and reliable tool to measure disease activity and damage in epidermolysis bullosa (EB). We aim to further validate the EBDASI by assessing its responsiveness to change. A pilot prospective longitudinal study was conducted in 6 patients with EB (3 with recessive dystrophic EB, 3 with junctional EB) and 1 patient with epidermolysis bullosa acquisita (EBA). The EBDASI was scored by an expert physician on at least two patient visits. 2 patients showed response to therapy. The patient with EBA receiving monthly rituximab infusions at a dosage of 375 mg/m2 of BSA for four consecutive months exhibited partial response, with an EBDASI activity score of 54 at baseline and 15 after the fourth infusion. Relapse 12 months post-infusion was observed, with an EBDASI activity score of 58. A patient with junctional EB commencing on a regimen of 150mg/day of thalidomide experienced a reduction in EBDASI activity score from 46 at baseline to 25 at month 3, which correlated with a reduction in pain from 8 to 5 according to a 10cm visual analogue scale. The other 5 EB patients with supportive management experienced stable EBDASI activity scores at follow-up of 3 to 12 months (mean 6 months). EBDASI damage scores were stable or worsened in all patients in the study. These findings confirm the usefulness of the EBDASI activity score as responsive to change in patients’ disease with treatment and over time. The EBDASI may be useful in quantifying disease severity in clinical practice and in upcoming trials which assess novel therapies in EB.