Treatment of Wilson disease with ammonium tetrathiomolybdate: IV. Comparison of tetrathiomolybdate and trientine in a double-blind study of treatment of the neurologic presentation of Wilson disease.
OBJECTIVE
To compare tetrathiomolybdate and trientine in treating patients with the neurologic presentation of Wilson disease for the frequency of neurologic worsening, adverse effects, and degree of neurologic recovery.


METHODS
A randomized, double-blind, controlled, 2-arm study of 48 patients with the neurologic presentation of Wilson disease. Patients either received 500 mg of trientine hydrochloride 2 times per day or 20 mg of tetrathiomolybdate 3 times per day with meals and 20 mg 3 times per day between meals for 8 weeks. All patients received 50 mg of zinc 2 times per day. Patients were hospitalized for 8 weeks, with neurologic and speech function assessed weekly; discharged taking 50 mg of zinc 3 times per day, and returned annually for follow-up.


METHODS
A university hospital referral setting.


METHODS
Primarily newly diagnosed patients with Wilson disease presenting with neurologic symptoms who had not been treated longer than 4 weeks with an anticopper drug.


METHODS
Treatment with either trientine plus zinc or tetrathiomolybdate plus zinc.


METHODS
Neurologic function was assessed by semiquantitative neurologic and speech examinations. Drug adverse events were evaluated by blood cell counts and biochemical measures.


RESULTS
Six of 23 patients in the trientine arm and 1 of 25 patients in the tetrathiomolybdate arm underwent neurologic deterioration (P<.05). Three patients receiving tetrathiomolybdate had adverse effects of anemia and/or leukopenia, and 4 had further transaminase elevations. One patient receiving trientine had an adverse effect of anemia. Four patients receiving trientine died during follow-up, 3 having shown initial neurologic deterioration. Neurologic and speech recovery during a 3-year follow-up period were quite good.


CONCLUSIONS
Tetrathiomolybdate is a better choice than trientine for preserving neurologic function in patients who present with neurologic disease.
Brewer
George J
GJ
Department of Human Genetics, University of Michigan Medical School, 5024 Kresge Bldg. II, Ann Arbor, MI 48109-0534, USA. brewergj@umich.edu
Askari
Fred
F
Lorincz
Matthew T
MT
Carlson
Martha
M
Schilsky
Michael
M
Kluin
Karen J
KJ
Hedera
Peter
P
Moretti
Paolo
P
Fink
John K
JK
Tankanow
Roberta
R
Dick
Robert B
RB
Sitterly
Julia
J
D000293:Adolescent; D000328:Adult; D000740:Anemia / Q000139:chemically induced / Q000503:physiopathology; D002614:Chelating Agents / Q000008:administration & dosage* / Q000009:adverse effects; D003300:Copper / Q000037:antagonists & inhibitors / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006527:Hepatolenticular Degeneration / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D007902:Length of Stay; D008297:Male; D008875:Middle Aged; D008982:Molybdenum / Q000008:administration & dosage* / Q000009:adverse effects; D012709:Serum Albumin / Q000187:drug effects / Q000378:metabolism; D013060:Speech / Q000187:drug effects / Q000502:physiology; D013064:Speech Disorders / Q000188:drug therapy / Q000503:physiopathology; D016896:Treatment Outcome; D014266:Trientine / Q000008:administration & dosage* / Q000009:adverse effects; D015032:Zinc / Q000627:therapeutic use
D002614:Chelating Agents; D012709:Serum Albumin; D003300:Copper; D008982:Molybdenum; C020809:tetrathiomolybdate; D015032:Zinc; D014266:Trientine