The value of pulse cyclophosphamide in ANCA-associated vasculitis: meta-analysis and critical review.
BACKGROUND
The study aimed at studying efficacy and adverse effects of pulse cyclophosphamide (pCyc) treatment and to compare it to continuous cyclophosphamide (cCyc) for induction of remission in ANCA-associated vasculitides from data in the published literature.


METHODS
A Medline search identified 14 studies, containing more than five patients. From the 11 non-randomized studies, data on outcome following pCyc treatment were extracted. Results were given as fraction of the number of evaluable patients. A meta-analysis was performed on the three prospective, randomized controlled trials to compare outcomes concerning remission, relapses, infection, leucopenia, death and renal failure in patients treated with pCyc as opposed to cCyc.


RESULTS
The 11 non-randomized studies comprised 202 patients receiving pCyc. Cyc pulses of 375-1000 mg/sqm/pulse were applied at weekly to monthly intervals with different concomitant prednisolone regimens and variable adjunctive therapy. Complete remission was achieved in 112/191, partial remission in 23/191 evaluable patients. Relapses occurred in 68/135 patients, 40/115 patients were non-responders. Leucopenia, infections, haemorrhagic cystitis, and deaths were rare. The meta-analysis, comprising 143 patients, showed that pCyc compared with cCyc treatment was significantly less likely to fail to induce remission (OR 0.29; 95% CI 0.12-0.73) and had a significantly lower risk of infection (OR 0.45; 95% CI 0.23-0.89) and leucopenia (OR 0.36; 95% CI 0.17-0.78). Relapses occurred slightly, although not statistically significantly, more often under pCyc treatment (OR 1.79; 95% CI 0.85-3.75). There were no differences in end-stage renal failure or deaths between the two regimens.


CONCLUSIONS
The currently available, rather sparse data show that pCyc is less toxic than cCyc therapy and is an at least equally potent inductor of remission, but possibly at the expense of a higher relapse rate. The existing data do not give sufficient information on outcomes as time to remission and relapse, irreversible damage or quality of life without which a treatment regimen cannot satisfactorily be evaluated today. A large prospective randomized controlled trial is needed to address these issues and their relative importance.
de Groot
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Department of Nephrology, Medical School Hannover, Germany. kirsten@de-grot.de
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Savage
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D019268:Antibodies, Antineutrophil Cytoplasmic / Q000378:metabolism*; D003520:Cyclophosphamide / Q000008:administration & dosage* / Q000009:adverse effects; D014890:Granulomatosis with Polyangiitis / Q000188:drug therapy / Q000276:immunology; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D007239:Infections / Q000209:etiology; D007970:Leukopenia / Q000209:etiology; D012074:Remission Induction; D014657:Vasculitis / Q000188:drug therapy* / Q000276:immunology*
D019268:Antibodies, Antineutrophil Cytoplasmic; D007166:Immunosuppressive Agents; D003520:Cyclophosphamide