Researchers aim to assess whether hydroxychloroquine is safer and more cost-effective than conventional immunosuppressive treatments in managing antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), according to study details published in Trials.
Autoimmune diseases like AAV are caused by an overactive immune system that results in small blood vessel inflammation. Multisystem organ damage may result, which can lead to failure and death; the mortality rate among patients with AAV is approximately twice that of the general population.
Immunosuppressive therapies can improve outcomes, but around half of patients still experience a relapse within 5 years. However, should immunosuppressants need to be withdrawn due to adverse effects, disease flares often occur, with an associated drop in quality of life.
“There is an unmet need for safe, effective therapies for non-severe AAV to reduce disease activity, prevent disease progression and damage accumulation and minimize drug toxicity,” the authors wrote.
Read more about AAV etiology
Hydroxychloroquine is a drug that has been proven to be safe and effective in treating autoimmune diseases such as Sjögren’s syndrome and systemic lupus erythematosus. Importantly, it is steroid sparing, meaning that patients do not need to worry about the resulting adverse effects of cumulative steroid doses. Despite its excellent track record in treating autoimmune disorders, the use of hydroxychloroquine has never been assessed in AAV.
The authors of this study thus seek to explore if the addition of hydroxychloroquine to background therapy can augment positive outcomes. They aim to conduct a double-blind, multicenter trial, called HAVEN, in which patients with AAV are randomized in a 1:1 ratio to receive hydroxychloroquine (400 mg daily, later adjusted to body weight and renal function) or placebo for 52 weeks. Ten visits will be scheduled across 60 weeks, during which clinicians will collect data on adherence to treatment, disease activity, clinical biomarkers, and quality of life.
The COVID-19 pandemic resulted in the delay of the trial, and the research team has extended the study period to cover lost time. They also revised the exclusion criteria to include patients who were admitted to critical care in the last 6 months due to COVID-19. Flexibility was added to trial visit windows in the event that a participant needed to self-isolate.
Read more about AAV treatment
The research team is currently working according to their latest protocol, amended on May 10, 2022. Recruitment for the trial is ongoing and is due to be completed by December 31, 2024.
“Despite concerns about the impact of COVID-19 on recruitment, the HAVEN trial hopes to show that the addition of hydroxychloroquine as an adjunctive therapy to standard of care therapies does reduce disease activity in patients with AAV,” the authors wrote.
Learoyd AE, Arnold L, Reid F, et al. The HAVEN study-hydroxychloroquine in ANCA vasculitis evaluation — a multicentre, randomised, double-blind, placebo-controlled trial: study protocol and statistical analysis plan. Trials. Published online April 6, 2023. doi:10.1186/s13063-023-07108-3