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Dermatology Advisor
Vascular Skin Disease
Hibah Khaja, PharmD June 27th, 2025
Pipeline Drugs for Vasculitis
Vasculitis refers to a group of autoimmune diseases that cause inflammation of the blood vessels. This inflammation can result in tissue damage and, in severe cases, lead to organ failure. The classification of vasculitis is primarily based on the size of the affected vessels, including small-, medium-, and large-vessel involvement.
Recent advancements have greatly improved the understanding and management of inflammatory conditions, paving the way for innovative therapeutic strategies targeting specific inflammatory pathways.1 Among these conditions, Kawasaki disease (KD), a type of medium-vessel vasculitis, has been highlighted in a newly updated scientific statement from the American Heart Association. This update showcases advances in early diagnosis, advanced cardiac imaging techniques, and the development of emerging anti-inflammatory treatments. It also emphasizes the critical role of timely intervention in mitigating the risk for coronary artery complications, which remain a significant concern in untreated cases.2
These advancements are vital for addressing the challenges of treating medium-vessel vasculitides, including polyarteritis nodosa (PAN) and KD. These conditions affect arterial integrity and can lead to life-threatening complications, particularly among pediatric patients.
Kawasaki disease is the most common cause of acquired heart disease among children in developed nations. In the United States, KD affects 18 to 25 out of every 100,000 children aged less than 5 years. Without prompt treatment, nearly 25% of affected individuals may develop coronary artery aneurysms, highlighting the need for early diagnosis and effective anti-inflammatory interventions.2 Advances in cardiovascular imaging and the identification of high-risk patient subgroups have paved the way for improved treatment algorithms, including the use of adjunctive biologic therapies for preventing long-term cardiovascular complications.2
Small-vessel vasculitis includes disorders such as granulomatosis with polyangiitis (GPA), eosinophilic granulomatosis with polyangiitis (EGPA), microscopic polyangiitis (MPA), and immunoglobulin A vasculitis (Henoch-Schönlein purpura). These conditions are primarily driven by immune system dysregulation, with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) playing a crucial role in GPA and MPA.3
In recent years, novel targeted therapies have been introduced to reduce reliance on corticosteroids, including complement inhibitors such as avacopan and biologics targeting eosinophilic pathways such as benralizumab.4,5 These emerging treatments are reshaping the management landscape, offering patients improved remission rates with reduced steroid-related adverse effects.5
Large-vessel vasculitis, encompassing conditions such as giant cell arteritis (GCA) — often linked to polymyalgia rheumatica (PMR) — and Takayasu arteritis (TAK), primarily affects the aorta and its major branches. These disorders can lead to serious vascular complications, including stenosis, aneurysms, and ischemic damage to organs.6 While corticosteroids have traditionally been the cornerstone of treatment, newer steroid-sparing agents such as Janus kinase (JAK) inhibitors are being actively explored for their potential to improve long-term disease control while minimizing corticosteroid-related toxicity.7
With clinical trials investigating novel immunomodulatory approaches, the therapeutic landscape for treating vasculitis continues to evolve, offering the potential for improved patient outcomes and better quality of life.
Small Vessel Vasculitis
Small vessel vasculitides, including GPA, EGPA, and MPA, are frequently linked to AAV. Emerging therapies for these conditions focus on enhancing remission rates while minimizing the adverse effects associated with traditional immunosuppressive treatments.
GPA, EGPA and MPA
Avacopan (CCX168): The C5a receptor inhibitor avacopan demonstrated significant efficacy for reducing glucocorticoid use while maintaining remission among patients with AAV, including GPA and MPA. In the phase 3 ADVOCATE trial (ClinicalTrials.gov Identifier: NCT02994927), patients who received avacopan achieved sustained remission at 52 weeks (65.7% vs 54.9% with standard therapy).4
Benralizumab: The anti-interleukin [IL]-5 receptor monoclonal antibody benralizumab demonstrated noninferiority to mepolizumab in the phase 3 MANDARA trial (ClinicalTrials.gov Identifier: NCT04157348), achieving remission at week 36 among 58% of patients with EGPA and enabling corticosteroid tapering to 4 mg/day or less in a greater percentage of patients.5
Iptacopan (LNP023): The oral complement factor B inhibitor iptacopan is being investigated in a phase 2 trial (ClinicalTrials.gov Identifier: NCT06388941) for its potential to reduce inflammation among patients with AAV. The trial is ongoing, with no published outcomes to date.
Low-dose naltrexone: The opioid receptor antagonist naltrexone is being investigated in the phase 2 LoDoNaVasc study (ClinicalTrials.gov Identifier: NCT03482479) for its potential to improve health-related quality of life (HRQOL) among patients with various vasculitides, including but not limited to GPA, MPA, and EGPA. The trial is ongoing, with no published outcomes to date.
Henoch-Schönlein Purpura
Rituximab, infliximab, tocilizumab: These biologics were being studied in the phase 3, multicenter, randomized, double-blind, placebo-controlled, modified-crossover BIOVAS trial (ClinicalTrials.gov Identifier: NCT05168475) evaluating the efficacy of infliximab, rituximab, and tocilizumab for the treatment of refractory non-ANCA-associated vasculitis (including Henoch-Schönlein purpura) among both adults and children. Though previously ongoing with no published outcomes, the BIOVAS trial was recently terminated due to withdrawal of funding.
Low-dose naltrexone: The phase 2 LoDoNaVasc study is also exploring the potential of naltrexone for enhancing HRQOL among patients with Henoch-Schönlein purpura. The trial is ongoing, with no published outcomes to date.
Medium-Vessel Vasculitis
Advancements in targeted therapies for medium vessel vasculitides, such as PAN and KD, have been limited. However, emerging research offers potential for progress in this area.
KD:
Defibrotide: The endothelial stabilizing agent defibrotide is being investigated in a phase 2 pilot study (ClinicalTrials.gov Identifier: NCT04777422) to evaluate its safety in combination with intravenous immunoglobulins (IVIG) among children with high-risk KD. The trial is ongoing, with no published outcomes to date.
Anakinra: The IL-1 receptor antagonist anakinra is being evaluated in the phase 3, multicenter, randomized, open-label ANACOMP trial (ClinicalTrials.gov Identifier: NCT04656184) to compare its efficacy and safety against a second IVIG infusion among patients with KD who failed to respond to initial standard IVIG treatment. Researchers aim to determine whether anakinra is superior in resolving fever, with the achievement of a body temperature below 38°C within 2 days of treatment initiation as the primary endpoint. The trial is ongoing, with no published outcomes to date.
PAN: Emerging therapies aim to enhance existing treatment approaches, particularly through biologics that target the tumor necrosis factor-alpha and IL-6 pathways. However, the absence of large-scale trials remains a significant limitation due to the rarity of the condition.
Rituximab, infliximab, tocilizumab: These biologics are being studied in the phase 3 BIOVAS trial evaluating the efficacy of infliximab, rituximab, and tocilizumab for the treatment of refractory non-ANCA-associated vasculitis (including PAN) among both adults and children. The trial is ongoing, with no published outcomes to date.
Low-dose naltrexone: The phase 2 LoDoNaVasc study is also exploring the potential of naltrexone for enhancing HRQOL among patients with PAN. The trial is ongoing, with no published outcomes to date.
Large-Vessel Vasculitis
Large vessel vasculitides, such as GCA and TAK, often require long-term treatment to prevent vascular complications.
GCA:
Abatacaept: The cytotoxic T-lymphocyte antigen 4 immunomodulator abatacept is being studied for GCA, showing potential for achieving remission and preventing relapses by modulating T-cell activation. In a phase 3, randomized, double-blind, placebo-controlled trial (ClinicalTrials.gov Identifier: NCT04474847), researchers are evaluating the efficacy of subcutaneous abatacept 125 mg per week among patients with newly diagnosed or relapsing GCA. The trial includes 62 patients randomly assigned in a 1:1 ratio to receive either abatacept or placebo. Patients achieving remission will remain on their assigned treatment for 12 months, after which treatment will be stopped. Those not in remission by month 3 or who relapse within the first 12 months will have the option to receive open-label abatacept for up to 12 months. This study is currently recruiting participants and the outcomes are yet to be determined.
Rituximab, infliximab, tocilizumab: Tocilizumab, already US Food and Drug Administration-approved for the treatment of GCA, is now the focus of new studies exploring its long-term outcomes and potential combination therapies. These biologics are being further investigated in the phase 3 BIOVAS trial evaluating the efficacy of infliximab, rituximab, and tocilizumab for managing refractory non-ANCA-associated vasculitis (including GCA) among both adults and children. The trial is ongoing, and outcomes have yet to be published.
Low-dose naltrexone: The phase 2 LoDoNaVasc study is also exploring the potential of naltrexone for enhancing HRQOL among patients with GCA. The trial is currently ongoing, with no published outcomes to date.
TAK:
Upadacitinib: The JAK inhibitor upadacitinib is being investigated in the phase 3, multicenter, randomized, double-blind, placebo-controlled SELECT-TAK study (ClinicalTrials.gov Identifier: NCT04161898) for its potential to improve outcomes among patients with TAK. Researchers are evaluating the efficacy and safety of upadacitinib in combination with a corticosteroid taper regimen compared with placebo. The study is ongoing, with no published outcomes to date.
Tofacitinib: The JAK inhibitor tofacitinib is currently being evaluated in a phase 3, prospective, randomized, double-blind, single-center trial (ClinicalTrials.gov Identifier: NCT05749666) comparing its efficacy and safety with prednisolone for the treatment of active TAK. The primary endpoint is the percentage of patients achieving complete response at week 24. Efficacy will be evaluated at weeks 4, 12, and 24, while safety is also monitored throughout the trial. The study is ongoing, with no published outcomes to date.
Rituximab, infliximab, tocilizumab: These biologics are being studied in the phase 3 BIOVAS trial evaluating the efficacy of infliximab, rituximab, and tocilizumab for the treatment of refractory non-ANCA-associated vasculitis (including TAK) among both adults and children. The trial is ongoing, with no published outcomes to date.
Low-dose naltrexone: The phase 2 LoDoNaVasc study is also exploring the potential of naltrexone for enhancing HRQOL among patients with TAK. The trial is currently ongoing, with no published outcomes to date.
PMR:
Secukinumab (AIN457): The IL-17A inhibitor secukinumab is currently being evaluated in a phase 3, multicenter, open-label extension of the REPLENISH study (ClinicalTrials.gov Identifier: NCT06331312). Researchers aim to assess the long-term efficacy, safety, and tolerability of secukinumab among patients with PMR, with a particular focus on achieving sustained glucocorticoid reduction without triggering disease flares. The trial is ongoing, with no published outcomes to date.
Editor’s Note: This article was updated on June 25, 2025, to reflect the termination of the BIOVAS trial.
This article originally appeared on Rheumatology Advisor
https://www.dermatologyadvisor.com/features/pipeline-drugs-for-vasculitis/