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
40 Years
80 Years
Both
Hand Osteoarthritis
Trial Information
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
of screening.
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.
Inclusion Criteria:
- Age: 40-80
- Men or women
- Digital osteoarthritis (DIP and PIP) according to ACR criteria (with recent X-ray,
dating from less than 6 months, of the hands showing radiological signs of digital
osteoarthritis)
- Symptomatic digital osteoarthritis for more than 3 months (at least every other day)
despite taking analgesics and NSAIDs (except when there are contraindications to the
latter therapeutic group)
- Osteoarthritis affecting more than three finger joints
- Pain more than 40 mm as evaluated by pain VAS (0-100 mm)
- No contraindication to anti-TNF alpha treatments
- No digital osteoarthritis surgery scheduled within the next 2 months
- Written informed consent
Exclusion Criteria:
- Pregnant women or women of reproductive potential without effective contraception
- Known hypersensitivity
- Patients having already been treated with an anti-TNF alpha
- Finger osteoarthritis secondary to inflammatory rheumatism
- Psoriasis
- Existence of painful syndrome of upper limbs likely to interfere with the monitoring
of pain (cervicobrachial neuralgia, incapacitating carpal tunnel syndrome, joint
disorders of the elbow or shoulder)
- Inflammatory rheumatism
- Contraindications to anti-TNF alpha agents: patients with suspected reactivation of
tuberculosis (phlyctenular IDR, past history of tuberculosis, chest X-ray deemed
suspect) or known leukopenia (< 3500 leukocytes), known hepatic cytolysis
(transaminases more than twice normal), a history of serious allergy, concomitant
infection, past history of serious systemic infection (septicemia), a history of
known cancer within the past 5 years, history of multiple sclerosis
- Skin disease incompatible with subcutaneous injection
- Anticoagulant (oral) or treatment with heparin at a curative dose
- Surgery scheduled within the coming 2 months
- Finger surgery scheduled within the coming 6 months
- Local injection of a corticosteroid in a symptomatic finger joint during the previous
month
- Local injection of hyaluronic acid in a symptomatic finger joint during the prior 3
months
- Treatment with a slow-acting anti-osteoarthritis agent initiated and colchicine
(amendment 26/06/2008) within the previous 3 months
- Oral corticosteroids
- Psychiatric illness
- Non-controlled diabetes "mellitus"
- Known viral hepatitis B or C, HIV infection
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment
Outcome Measure:
Level of Pain on visual analogue scale
Outcome Time Frame:
4 weeks following the last injection
Safety Issue:
Yes
Principal Investigator
Xavier Chevalier, PU-PH
Investigator Role:
Principal Investigator
Investigator Affiliation:
AP-HP
Authority:
France: Ministry of Health
Study ID:
P 051007
NCT ID:
NCT00597623
Start Date:
January 2008
Completion Date:
December 2010
Related Keywords:
- Hand Osteoarthritis
- Osteoarthritis
- Hand
- Tumor Necrosis Factor-alpha inhibitors
- Biological Therapy
- Osteoarthritis
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