A double-blind, placebo-controlled trial of low dose infliximab in ankylosing spondylitis.
OBJECTIVE
The tumor necrosis factor-alpha (TNF-alpha) inhibitor infliximab (IFX) has been proven effective for the treatment of ankylosing spondylitis (AS). The primary objective of this double-blind, placebo-controlled study was to assess the safety and efficacy of low-dose (3 mg/kg q8w) IFX therapy in AS.


METHODS
In the 12-week double-blind phase of the study, patients (N = 76) were randomized to infusions of placebo or IFX (3 mg/kg) at Weeks 0, 2, and 6. The primary endpoint was 20% improvement in ASsessments in Ankylosing Spondylitis criteria (ASAS20) at 12 weeks. In the open-label extension phase, all patients received scheduled IFX infusions (q 8 weeks) up to 46 weeks. Patients who did not meet target response criteria (i.e., BASDAI score did not improve by at least 50% and was > 3) at Weeks 22 or 38 had a dose increase to IFX 5 mg/kg.


RESULTS
At 12 weeks, 53.8% of IFX-treated patients achieved ASAS20, compared with 30.6% of placebo-treated patients (p = 0.042). IFX-treated patients showed significant improvement in measures of disease activity, spinal mobility, and quality of life over the course of the study. During the extension phase, 68% of patients in the IFX group did not meet the clinical target and had an increase in the dose of IFX to 5 mg/kg by 38 weeks. In general, IFX was safe and well tolerated. Ten patients withdrew from the study for various reasons, with only 2 (2.6%) attributed to adverse events.


CONCLUSIONS
IFX 3 mg/kg was effective in reducing the signs and symptoms of active AS, and was generally safe and well tolerated. Dose escalation to 5 mg/kg every 8 weeks was warranted in most patients to achieve the target clinical response of the study.
University of Toronto, Toronto Western Hospital, 1E-423, 399 Bathurst Street, Toronto, Ontario M5T 2S8, Canada. robert.inman@uhn.on.ca
Robert D
RD
Inman
Walter P
WP
Maksymowych
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006304:Health Status; D006801:Humans; D000069285:Infliximab; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D013167:Spondylitis, Ankylosing / Q000188:drug therapy* / Q000503:physiopathology; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*; D055815:Young Adult
D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab