Intermittent cyclophosphamide with prednisone versus placebo for polyneuropathy with IgM monoclonal gammopathy.
BACKGROUND
The best treatment for polyneuropathy associated with IgM monoclonal gammopathy (MGUS) is unknown. Oral cyclophosphamide combined with prednisone showed limited efficacy in a previous open label pilot study. We therefore performed a double-blind, randomized, placebo-controlled study of combined oral cyclophosphamide and prednisone in IgM MGUS polyneuropathy.


METHODS
Thirty-five patients with progressive IgM MGUS polyneuropathy were included. After stratification for anti-MAG antibodies patients were randomized to oral cyclophosphamide 500 mg once daily for 4 days combined with oral prednisone 60 mg once daily for 5 days (treatment) (n = 16), or placebo (n = 19), repeated every 28 days for six times. Primary outcome was improvement of the Rivermead Mobility Index (RMI). Secondary outcomes were improvement of the modified Rankin scale, Medical Research Council and sensory sum scores, levels of M protein, EMG, and Short Form-36 scale after treatment. Patients were examined at 0, 6, 12, 18, and 24 months.


RESULTS
After 6 months of treatment and at later follow-up, no difference in change of the RMI between the two groups was observed. Change of the Rankin scale was similar in both groups. Other outcome parameters showed more improvement in the treatment group: the MRC sum score improved more from 6 to 24 months after treatment; the sensory sum score improved more at 6 months; the SF 36 mean health change score and physical role score improved more; and the median nerve distal conduction (abductor pollicis brevis muscle) improved more in the treatment group. The most common adverse event was nausea.


CONCLUSIONS
Compared with placebo treatment, this first double-blind randomized trial with cyclophosphamide and prednisone in IgM MGUS polyneuropathy showed no beneficial effect on the functional scales, but a beneficial effect on muscle strength and sensation was observed.
Niermeijer
J M F
JM
Department of Neurology and Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, The Netherlands. j.m.f.niermeijer@umcutrecht.nl
Eurelings
M
M
van der Linden
M W
MW
Lokhorst
H M
HM
Franssen
H
H
Fischer
K
K
Teunissen
L L
LL
van den Berg
L H
LH
Schobben
F
F
Wokke
J H J
JH
Notermans
N C
NC
D000203:Activities of Daily Living; D000368:Aged; D018592:Cross-Over Studies; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000627:therapeutic use*; D003907:Dexamethasone / Q000627:therapeutic use; D018450:Disease Progression; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D004576:Electromyography; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007075:Immunoglobulin M; D008297:Male; D008875:Middle Aged; D053580:Muscle Strength / Q000187:drug effects; D010265:Paraproteinemias / Q000150:complications*; D011115:Polyneuropathies / Q000188:drug therapy* / Q000209:etiology; D011241:Prednisone / Q000008:administration & dosage / Q000627:therapeutic use*; D011788:Quality of Life; D012677:Sensation / Q000187:drug effects; D012720:Severity of Illness Index; D016896:Treatment Outcome
D007075:Immunoglobulin M; D003907:Dexamethasone; D003520:Cyclophosphamide; D011241:Prednisone