Randomized Double Blind Placebo-controlled Trial of the Efficacy of an Anti-TNF Alpha Agent (Adalimumab, Humira®) in Patients With Incapacitating Hand Osteoarthritis Refractory to Usual Treatment
Objective: To demonstrate the efficacy of two subcutaneous injections of anti-TNF alpha
(adalimumab) in patients with DO refractory to usual treatments (NSAIDs - analgesics).
Design: Randomized placebo-controlled multicenter (20 sites (amendment 18/12/2008)) trial
Trial duration: 6 months follow-up per patient, total trial duration: 12 months
Number of patients: 84(up)
Dose of administration: Two subcutaneous injections separated by a 2-week interval of
either adalimumab or placebo. Therapeutic precautions inherent to the prescription of
anti-TNF alpha are based upon those recommended in rheumatoid arthritis. With only two
injections of anti-TNF alpha, the risk of complications (infectious in particular) inherent
to the anti-TNF alpha appears to be extremely slight.
Patient selection: Patients with digital osteoarthritis (DIP and PIP) according to American
College of Rheumatology (ACR) criteria (with a recent X-ray, less than 6 months, of the
hands, showing signs of digital osteoarthritis), symptomatic for more than 3 months (at
least three finger joints) and scored more than 40 mm on a pain visual analog scale (VAS)
despite use of a level 1 analgesic (acetaminophen: 4 g daily) andNSAIDs. Main Exclusion
criteria are contraindications to anti-TNF alpha according to international guidelines.
Methods: Patients will be seen at a screening visit, then during treatment administration
(W0 and W2) and at follow-up visits: W6, 10, 14 and 26. NSAIDs will be stopped at the time
Efficacy evaluation: The efficacy endpoint is improvement in pain on a pain VAS at
different times of assessment (primary endpoint at W6). A more than 50% improvement, in
comparison with baseline, will be considered to be significant. Secondary endpoints are:
number of tender joints, number of swollen joints, morning stiffness, global assessment of
handicap by patient, global assessment of handicap by physician, the DREISER'S
algofunctional index, Cochin hand index, weekly evolution of pain ( patient record), and
recording of analgesic use (acetaminophen or NSAIDs).
Statistical data: Statistical analysis will be performed on the inter-group difference in
the intention-to-treat population. khi-2 will be used only for criteria number 1.
Anticipated result: Significant superiority of adalimumab over placebo which would provide
a therapeutic solution in difficult-to-treat patients with hand OA.
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment
Level of Pain on visual analogue scale
4 weeks following the last injection
Xavier Chevalier, PU-PH
France: Ministry of Health