Background Patients with giant cell arteritis (GCA) refractory to standard immunosuppressive therapy including glucocorticoids (GC) and GC-sparing agents (methotrexate, azathioprine) may comprise a significant clinical problem with a high risk of GC-related adverse effects. There are currently no recommendations or guidelines for this setting, and treatment has to rely largely on clinical judgement and personal experience of the responsible physicians.
Objectives To evaluate efficacy and safety of cyclophosphamide (CYC) for remission induction in GCA patients with persistent disease activity despite standard immunosuppressive treatment.
Methods Individuals treated for persistently active GCA unresponsive to treatment with GC plus at least either methotrexate or azathioprine for a minimum of 3 months and unable to reduce daily GC dose to <10 mg prednisolone equivalent were identified from the medical charts of 3 tertiary rheumatological centers between 1990 and 2009. Relevant clinical data including a detailed disease history; previous treatment; signs of disease activity (clinical, laboratory, imaging); course of GC dose; relapse rate; treatment-related adverse events; and survival were recorded. Since all patients had been refractory to standard therapy, a matched control group could not be defined.
Results Thirty-five individuals satisfying the above stated criteria were identified; of these, data from 31 patients completing CYC treatment were available for analysis. CYC was administered either i.v. (7.5 infusions per patient at a mean interval of 23 days, mean cumulative dose 9.2 g) or orally (mean 1.6 mg/kg body weight per day, cumulative dose mean 14.4 g). Twenty-eight patients (90.3%) responded with substantial improvement of disease activity and sustained reduction of daily prednisolone intake to <10 mg (mean reduction -13.1 mg or -51.6%, p<0.001). Twelve months later, doses <7.5 or <5 mg were achieved in 89.3% and 67.7% of these patients on maintenance immunosuppressive treatment, respectively. Relapses occurred in 12 patients after a median of 20.5 months and could be controlled by a temporary GC dose increase or/and intensification of GC-sparing treatment, including 3 cases of CYC re-treatment (additive cumulative dose ≤6 g in all cases), again leading to a good response. Survival over 5 years was similar to expected rates of the general population. Adverse events comprised transient leucopenia (at least moderate, n=6), infections (n=7; 2 requiring hospital admission), allergic reactions to mesna (n=2) and 1 case of hemorrhagic cystitis. More adverse effects (50% of cases) were observed during oral CYC intake.
Conclusions This study is the first to provide data on CYC treatment of a larger cohort of well-characterized GCA patients. CYC can be considered a therapeutic option for remission induction in GCA refractory to standard immunosuppressive treatment. Although severe adverse events were recorded, overall tolerability in this elderly patient population was acceptable when weighed against the potential risks of long-term treatment with high GC doses. Use of the less toxic i.v. application appears to be effective in most cases and should be considered as the preferred application form in all cases.
Disclosure of Interest None Declared
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