Sustained benefits of infliximab therapy for dermatologic and articular manifestations of psoriatic arthritis: results from the infliximab multinational psoriatic arthritis controlled trial (IMPACT).
OBJECTIVE
To investigate the efficacy and tolerability of infliximab therapy for the articular and dermatologic manifestations of active psoriatic arthritis (PsA).


METHODS
One hundred four patients with PsA in whom prior therapy with at least 1 disease-modifying antirheumatic drug (DMARD) had failed were recruited into this investigator-initiated, multicenter, randomized, double-blind, placebo-controlled clinical trial. During the initial blinded portion of the study, patients received infusions of infliximab (5 mg/kg) or placebo at weeks 0, 2, 6, and 14. After week 16, patients initially assigned to receive placebo crossed over to receive infliximab 5 mg/kg every 8 weeks through week 50, while patients initially randomized to infliximab continued to receive active treatment at the same dose through week 50. The primary efficacy outcome was achievement of the American College of Rheumatology 20% criteria for improvement in rheumatoid arthritis (ACR20) at week 16. Additional predefined clinical efficacy assessments included the Psoriasis Area and Severity Index (PASI) score, the ACR50 and ACR70 criteria, the Disease Activity Score in 28 joints, the Health Assessment Questionnaire, ratings of enthesitis and dactylitis, and the Psoriatic Arthritis Response Criteria score.


RESULTS
The proportion of infliximab-treated patients who achieved an ACR20 response at week 16 (65%) was significantly higher than the proportion of placebo-treated patients who achieved this response (10%). In addition, 46% of infliximab-treated patients achieved an ACR50 response, and 29% achieved an ACR70 response; no placebo-treated patient achieved these end points. Among patients who had PASI scores of >/=2.5 at baseline, 68% of infliximab-treated patients achieved improvement of >/=75% in the PASI score at week 16 compared with none of the placebo-treated patients. Continued therapy with infliximab resulted in sustained improvement in articular and dermatologic manifestations of PsA through week 50. The incidence of adverse events was similar between the treatment groups.


CONCLUSIONS
Therapy with infliximab at a dose of 5 mg/kg significantly improved the signs and symptoms of arthritis, psoriasis, dactylitis, and enthesitis in patients with active PsA that had been resistant to DMARD therapy. With continued infliximab treatment, benefits were sustained through 50 weeks. The benefit-to-risk ratio appeared favorable in this study population.
Antoni
Christian E
CE
Friedrich-Alexander University, Erlangen-Nuremberg, Germany. christian.antoni@spcorp.com
Kavanaugh
Arthur
A
Kirkham
Bruce
B
Tutuncu
Zuhre
Z
Burmester
Gerd R
GR
Schneider
Udo
U
Furst
Daniel E
DE
Molitor
Jerry
J
Keystone
Edward
E
Gladman
Dafna
D
Manger
Bernhard
B
Wassenberg
Siegfried
S
Weier
Ralf
R
Wallace
Daniel J
DJ
Weisman
Michael H
MH
Kalden
Joachim R
JR
Smolen
Josef
J
D000328:Adult; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D015535:Arthritis, Psoriatic / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D000069285:Infliximab; D007262:Infusions, Intravenous; D007596:Joints / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D011565:Psoriasis / Q000188:drug therapy* / Q000473:pathology; D012720:Severity of Illness Index; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D000069285:Infliximab