Background/Purpose:

To assess retrospectively the efficacy and safety of hydroxychloroquine in patients with ANCA associated vasculitis.

There is an unmet need for a corticosteroid sparing, non-toxic therapy in ANCA vasculitis (AAV), as up to 50% of patients relapse by 5 years and 20% have sub-optimal disease control. Hydroxychloroquine (HCQ) has been effective and safe in autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis but no systematic studies have been carried out to assess its role in vasculitis. There is mechanistic rationale for the effectiveness of HCQ in AAV, in view of its effect on immune mediators involved in vasculitis pathogenesis including Toll-like receptors, pro-inflammatory cytokines, autoreactive B and T lymphocytes.

Methods: Patients were identified by searching our departmental vasculitis databases  and electronic clinical records. Thirty patients received HCQ +/- corticosteroids and immunosuppressants. We assessed the effect of HCQ on clinical symptoms and corticosteroid doses required.

Results: Thirty patients with ANCA+ vasculitis were treated with hydroxychloroquine (median dose 400 mg daily) for an average of 4.6 years.  Median age was 56.5 years.

Fifteen patients had a diagnosis of granulomatosis with polyangiitis (GPA) with +PR3-ANCA, whilst 13 were diagnosed with microscopic polyangiitis (MPA) with +MPO-ANCA and 2 patients had eosinophilic granulomatosis with polyangiitis (eGPA) with +MPO-ANCA.

The systems involved were: joints (20 patients), kidneys (12), ear-nose-throat (11), skin (11), eyes (5), lungs (4), peripheral nerves (3) and gastrointestinal system (1). Twenty-nine out of 30 patients were treated with other maintenance immunomodulatory agents in addition to HCQ (See Table 1).

Twenty three out of 30 patients (76.7%) reported benefits attributed to HCQ ranging from amelioration of joint pains (n=17) to reduction of corticosteroid doses (4), frequency of vasculitic flares (3) and fatigue (1). The effects of HCQ were unclear in 6 patients and 1 reported no symptomatic improvement.

Two patients experienced transient gastrointestinal side effects with HCQ, 1 patient developed haemolysis associated with rise in bilirubin, 1 asymptomatic QT interval prolongation resulting in discontinuation of HCQ. No major other adverse events were reported.

Conclusion: The majority of patients reported symptomatic benefits associated with HCQ treatment, especially improvement of joint pains. Vasculitic relapses were less frequent in some patients, with a reduction in corticosteroid doses. HCQ was used mostly as adjunctive therapy in addition to other immunomodulatory agents and was usually well tolerated. Future randomized controlled clinical trials are needed to establish the role of HCQ in ANCA+ vasculitis.