Treatment of polyarteritis nodosa and microscopic polyangiitis with poor prognosis factors: a prospective trial comparing glucocorticoids and six or twelve cyclophosphamide pulses in sixty-five patients.
OBJECTIVE
Because the optimal cyclophosphamide (CY) treatment duration for severe polyarteritis nodosa (PAN) without virus infection and microscopic polyangiitis (MPA) has not been established, we conducted a trial to compare the effectiveness of 6 versus 12 CY pulses given in combination with corticosteroids (CS).


METHODS
Sixty-five (18 PAN, 47 MPA) previously untreated patients were randomized to receive 12 (n = 34) or 6 (n = 31) CY pulses combined with CS. PAN and MPA were histologically proven or met ACR criteria. All patients presented >or=1 factor of severity according to the five factor score (FFS). CY pulses were administered every 2 weeks for 1 month, then every 4 weeks. The end point of the study was the number of events (relapses and/or deaths) occurring in each group, analyzed according to an intention-to-treat strategy. The outcome was evaluated by Cox proportional hazards analysis.


RESULTS
The baseline characteristics were similar for both groups. The mean (+/- SD) followup was 32 +/- 21 months. Survival analysis showed a significantly lower relapse probability (P = 0.02; hazards ratio [HR] = 0.34) and higher event-free survival (P = 0.02, HR = 0.44) for the 12 CY-pulse group while the mortality rates were not significantly different (P = 0.47).


CONCLUSIONS
These results suggest that 6 CY pulses are less effective than 12 CY pulses to treat severe PAN and MPA, particularly with respect to the risk of relapses.
Guillevin
Loïc
L
Hôpital Avicenne, Assistance Publique-Hôpitaux de Paris, Université Paris-Nord, Bobigny, France. loic.guillevin@avc.ap-hop-paris.fr
Cohen
Pascal
P
Mahr
Alfred
A
Arène
Jean-Pierre
JP
Mouthon
Luc
L
Puéchal
Xavier
X
Pertuiset
Edouard
E
Gilson
Brigitte
B
Hamidou
Mohamed
M
Lanoux
Patricia
P
Bruet
Alain
A
Ruivard
Marc
M
Vanhille
Philippe
P
Cordier
Jean-François
JF
D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D003520:Cyclophosphamide / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D005500:Follow-Up Studies; D005938:Glucocorticoids / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D008297:Male; D008833:Microcirculation; D008875:Middle Aged; D010488:Polyarteritis Nodosa / Q000188:drug therapy* / Q000401:mortality; D011379:Prognosis; D011446:Prospective Studies; D020551:Pulse Therapy, Drug; D016019:Survival Analysis; D016896:Treatment Outcome
D018501:Antirheumatic Agents; D005938:Glucocorticoids; D003520:Cyclophosphamide