**Background**
Granulomatosis with polyangiitis (GPA) is a rare ANCA-associated vasculitis with an annual incidence ranging from 1 in 84,000 to 475,000 persons and a global prevalence of 20–150 cases per million. It most commonly presents in individuals aged early 40s to late 60s and is more frequent in Caucasian populations. Clinical presentation typically begins with upper respiratory tract symptoms, progressing to vasculitis-related manifestations such as arthralgia, neuritis, and cutaneous vasculitis; 60–80% of patients develop renal symptoms due to necrotizing glomerulonephritis. Pharmacological management aims at remission induction followed by maintenance, using drugs such as cyclophosphamide, glucocorticoids, rituximab, methotrexate, mycophenolate mofetil, and azathioprine. Most drugs are used off-label except rituximab (approved for severe GPA in 2011) and avacopan. Despite the availability of treatment guidelines, no prior study has systematically reviewed the clinical trial pipeline for GPA. This study aimed to fill that gap by identifying and characterizing clinical trials from two major repositories.
**Methods**
The authors searched Clinicaltrials.gov and the International Clinical Trials Registry Platform (ICTRP) from inception until 25 September 2022 using the keywords 'granulomatosis with polyangiitis' and 'Wegener's granulomatosis'. Studies were included if they recruited a GPA population and investigated pharmacological treatment, even if not exclusively GPA. Vaccine studies were excluded. Data were collected on study status, results availability, population (GPA-only vs. broader), study design (observational vs. interventional), masking, allocation, interventional model, purpose, phase, and international collaboration. Each drug was recorded and grouped by pharmacological class: immunosuppressants, corticosteroids, monoclonal antibodies (MABs), selective T-cell costimulation blockers, BAFF-antagonists, TNF-alpha inhibitors, anti-lymphocyte immunoglobulins, antibiotics, and hematopoietic agents. Disease severity (severe, non-severe, or all types) and treatment scope (remission induction, maintenance, or both) were extracted where possible; if not specified, all severity types and remission induction were assumed. Descriptive analyses were performed using STATA.
**Key Results**
A total of 137 studies were identified, of which 108 (79%) concerned GPA. Of these, 67 (62%) enrolled GPA patients to investigate pharmacotherapy. Among the 67 studies, 25 focused exclusively on GPA, while 42 included GPA among other populations. Most studies (52%) were completed, 12% were recruiting, and 13% had unknown status. Only 28% of studies had results available. The majority (93%) were interventional; 34% were phase II, 24% phase III, and 18% phase IV. Most studies included all severity types (76%), with only 8% focusing on mild disease and 12% on severe disease. The scope was remission induction in 49% of studies, remission maintenance in 27%, and both in 8%. The median enrolled population size was 60 patients (25th–75th percentile: 27.5–140). The most investigated drug class was non-corticosteroid immunosuppressants (68.7%), followed by MABs (47.8%) and corticosteroids (46.3%). Among individual drugs, prednisolone was most common (26.9%), followed by rituximab (28.4%), cyclophosphamide (20.9%), and azathioprine (17.9%). Only one observational study was identified, which investigated prednisone and cyclophosphamide followed by methotrexate in 100 patients.
**Clinical Implications**
This review reveals a limited number of clinical trials for GPA, with most including all severity types despite clinical guidelines recommending severity-specific treatment. The predominance of remission induction trials (49%) and the small number focusing on remission maintenance (27%) or drug discontinuation highlight important evidence gaps. The low rate of results publication (28%) underscores a need for greater transparency. The heavy reliance on off-label drugs (except rituximab and avacopan) emphasizes the importance of drug repurposing and the need for robust evidence to support optimal use. Future research should prioritize severity-specific trials, long-term observational studies, and improved data sharing to better inform clinical practice.