Evaluation of Nomacopan for Treatment of Bullous Pemphigoid : A Phase 2a Nonrandomized Controlled Trial

This study's aim was to determine the relationship between Dermatology Life Quality Index (DLQI) scores and a Global Question (GQ) concerning patients' views of the overall impairment of their skin-related quality of life (QoL), and to express this relationship by identifying bands of DLQI scores equivalent to each GQ descriptor. A DLQI questionnaire and the GQ were mailed to 3834 adult general dermatology outpatients. There were 1993 (52%) responses: male 841; female 1152. Mean DLQI score = 4.86 (range 0-30, standard deviation (SD) = 5.83). Mean GQ score = 1.22 (range 0-4, SD = 1.20). The mean, mode, and median of the GQ scores for each DLQI score were used to devise several sets of bands of DLQI scores, and kappa coefficients of agreement calculated. The set proposed for adoption is: DLQI scores 0-1 = no effect on patient's life (GQ = 0, n = 754); DLQI scores 2-5 = small effect on patient's life (GQ = 1, n = 611); DLQI scores 6-10 = moderate effect on patient's life (GQ = 2, n = 327); DLQI scores 11-20 = very large effect on patient's life (GQ = 3, n = 242); DLQI scores 21-30 = extremely large effect on patient's life (GQ = 4, n = 59); kappa coefficient 0.489. Banding of the DLQI will aid the clinical interpretation of an individual's DLQI score and allow DLQI scores to inform clinical decisions.

Alternative C activation is involved in the pathogenesis of ANCA-associated vasculitis. However, glucocorticoids used as treatment contribute to the morbidity and mortality of vasculitis. We determined whether avacopan (CCX168), an orally administered, selective C5a receptor inhibitor, could replace oral glucocorticoids without compromising efficacy. In this randomized, placebo-controlled trial, adults with newly diagnosed or relapsing vasculitis received placebo plus prednisone starting at 60 mg daily (control group), avacopan (30 mg, twice daily) plus reduced-dose prednisone (20 mg daily), or avacopan (30 mg, twice daily) without prednisone. All patients received cyclophosphamide or rituximab. The primary efficacy measure was the proportion of patients achieving a ≥50% reduction in Birmingham Vasculitis Activity Score by week 12 and no worsening in any body system. We enrolled 67 patients, 23 in the control and 22 in each of the avacopan groups. Clinical response at week 12 was achieved in 14 of 20 (70.0%) control patients, 19 of 22 (86.4%) patients in the avacopan plus reduced-dose prednisone group (difference from control 16.4%; two-sided 90% confidence limit, −4.3% to 37.1%; P =0.002 for noninferiority), and 17 of 21 (81.0%) patients in the avacopan without prednisone group (difference from control 11.0%; two-sided 90% confidence limit, −11.0% to 32.9%; P =0.01 for noninferiority). Adverse events occurred in 21 of 23 (91%) control patients, 19 of 22 (86%) patients in the avacopan plus reduced-dose prednisone group, and 21 of 22 (96%) patients in the avacopan without prednisone group. In conclusion, C5a receptor inhibition with avacopan was effective in replacing high-dose glucocorticoids in treating vasculitis.

Pemphigoid diseases are a group of well defined autoimmune disorders that are characterised by autoantibodies against structural proteins of the dermal-epidermal junction and, clinically, by tense blisters and erosions on skin or mucous membranes close to the skin surface. The most common of these diseases is bullous pemphigoid, which mainly affects older people and the reported incidence of which in Europe has more than doubled in the past decade. Prognosis and treatments vary substantially between the different disorders and, since clinical criteria are usually not sufficient, direct immunofluorescence microscopy of a perilesional biopsy specimen or serological tests are needed for exact diagnosis. In eight pemphigoid diseases the target antigens have been identified molecularly, which has allowed the development of standard diagnostic assays for detection of serum autoantibodies-some of which are commercially available. In this Seminar we discuss the clinical range, diagnostic criteria, diagnostic assay systems, and treatment options for this group of diseases. Copyright © 2013 Elsevier Ltd. All rights reserved.