Objectives: The type I interferon pathway is a promising target for treatment of patients with systemic sclerosis (SSc). Here, we describe the design of a multinational, randomised phase 3 study to Determine the effectiveness of the type I interferon receptor antibody, Anifrolumab, In SYstemic sclerosis (DAISY).
Methods: DAISY includes a 52-week double-blind, placebo-controlled treatment period, a 52-week open-label active treatment period, and a 12-week safety follow-up period. The patient population includes a planned 306 adults with limited or diffuse cutaneous active SSc who satisfied American College of Rheumatology/European Alliance of Associations for Rheumatology 2013 SSc criteria. Use of standard immunosuppressants, including mycophenolate mofetil, at a stable dose prior to randomisation is permitted in addition to weekly subcutaneous anifrolumab or placebo. Efficacy will be assessed at Week 52 via Revised-Composite Response Index in SSc (CRISS)-25 response (primary endpoint). Lung function and skin thickness will be assessed via change from baseline in forced vital capacity in patients with SSc-associated interstitial lung disease and modified Rodnan Skin Score, respectively (key secondary endpoints).
Conclusions: The DAISY trial will evaluate the efficacy and safety of anifrolumab as a first-in-class treatment option for patients with both limited and diffuse cutaneous SSc and will provide insight into the contributions of type I interferon to SSc pathogenesis. Revised-CRISS-25 can account for improvement and worsening in a broad set of validated clinical measures beyond lung function and skin thickness, including clinician- and patient-reported outcomes, capturing the heterogeneity of SSc.
Systemic sclerosis is a chronic autoimmune disease that leads to inflammation and scarring of the skin and internal organs, especially the lungs. Systemic sclerosis and lupus are both associated with increased interferon signalling, which is usually triggered by viral infections, but is related to damaging inflammation in these diseases. Anifrolumab, a drug that blocks interferon signalling, is already used to treat patients with lupus (also known as SLE), so it could potentially be used to treat patients with systemic sclerosis. This publication details the DAISY study design and explains why it is needed. This study will follow 2 groups of 153 patients with systemic sclerosis over 2 years. During the first year, in addition to any standard immunosuppressant therapy, the groups will receive weekly injections of either anifrolumab or “dummy drug” (placebo). In the second year, all patients will receive anifrolumab with their standard immunosuppressant therapy. Multiple factors will be considered to evaluate the efficacy of anifrolumab treatment, including clinical measurements of skin thickness and lung function, and questionnaires completed by clinicians and patients to report on patient health and their everyday function during treatment. The DAISY study will investigate the efficacy and safety of anifrolumab treatment in a diverse group of patients with systemic sclerosis who currently have limited options for effective treatment. The study will evaluate the impact of anifrolumab treatment on multiple aspects of the disease, and how patients feel about their overall health-related quality of life.