Efficacy Study of an Anti-Tumor Necrosis Factor (TNF) Alpha Agent in Patients With Hand Osteoarthritis
Efficacy Study of an Anti-Tumor Necrosis Factor (TNF) Alpha Agent in Patients With Hand Osteoarthritis
Digital osteoarthritis (DO) which affects the interphalangeal joints and the
 Metacarpophalangeal (MCP) of the thumb is a common disease, the prevalence of which increases
 with age (36% of the population aged over 70). Certain forms of DO with clinical
 manifestations involving inflammatory features are particularly refractory to usual
 treatments (analgesics, NSAIDs, braces and local injections). The mechanism of osteoarthritis
 involves two major cytokines: interleukin-1 beta and tumor necrosis factor alpha. TNF alpha
 is particularly involved in the inflammation process.

 The aim of the present study is to study the efficacy of TNF alpha blockers (2 injections of
 adalimumab compared to placebo injections in patients with severe and refractory hand
 osteoarthritis.

 We hope that such new therapeutic option may induce substantial pain relief.
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