Does glucocorticosteroid-resistant large-vessel vasculitis (giant cell arteritis and Takayasu arteritis) exist and how can remission be achieved? A critical review of the literature.

OBJECTIVES: The mainstay in the treatment of the large-vessel vasculitides giant cell arteritis (GCA) and Takayasu arteritis (TA) are glucocorticosteroids (GC) for induction of remission as well as for its maintenance in low doses for 1 to 2 years. However, clinical practice includes GC-resistant cases without sufficient response to standard GC for induction of remission and GC-dependent cases where a dose reduction of GC without relapse is impossible after successful induction of remission. The aim of this study was to evaluate the data on treatment options in these situations.

METHODS: A literature search in PubMed matching the terms TA and GCA as well as temporal arteritis with all possible immunosuppressive and biological agents as well as with the terms 'treatment, therapy and management' was performed.

RESULTS: Sixty-four publications were found. Five case series described large cohorts of patients with GCA (n=2) or TA (n=3) showing that 40.8% to 48% of GCA patients and 46% to 84% of TA patients require additional immunosuppressive agents to achieve remission and taper GC. Most were on biologic agents (mainly infliximab, 24 publications/123 patients), followed by methotrexate (MTX) (14/113), cyclophosphamide (CYC) (9/27), azathioprine (AZA) (8/51), cyclosporine A (CSA) (6/47), mycophenolate mofetil (MMF) (3/32), leflunomide (LEF) (2/2), chlorambucil (1/1) and antimalarials (1/36). There were also 2 case reports on autologous stem cell transplantation. The distribution of the two entities TA and GCA was as follows: MTX: 98% GCA, 2% TA; IFX: 26.8% GCA, 73.2% TA; CYC: 70.4% GCA, 29.6% TA; AZA: 100% GCA; LEF: 100% TA; MMF: 100% TA; antimalarials: 100% GCA, autologous stem cell transplantation: 100% TA. A distinction between GC-resistant and GC-dependent cases could not be made from the data available. However, 50 (79%) of the publications described GC-resistant cases. Whereas almost all case reports and retrospective case series (with the exception of CSA) revealed steroid-sparing effects, the 3 prospective randomised trials and 2 open prospective controlled trials on MTX gave conflicting results. However, a recent meta-analysis which recalculated the original data resulted in superiority of MTX after 24 months, there were less relapses and lower GC doses in the MTX group. The prospective controlled IFX trial where IFX was randomised against placebo after GC-induced remission of GCA did not show advantages for IFX over GC alone for maintenance of remission. The prospective controlled ETA trial, which comprised 17 GCA patients, showed small, non-significant advantages but was too small to draw definite conclusions.

CONCLUSIONS: Although GCA is the commonest systemic vasculitis, prospective randomised trials on steroid sparing agents are rare and mostly included only small patient numbers. Inclusion and response criteria were heterogeneous, and observation periods and follow-up were often short. Criteria for GC-resistance or GC-dependence and for disease remission have not been uniformly defined. There is still an urgent need for prospective randomised trials with larger patient groups, longer follow-up and well defined inclusion criteria and criteria for response and relapse, using standardised disease activity scoring systems, in order to be able to give evidence-based recommendations for patients not responding to GC alone in the future.