Efficacy Study of an Anti-Tumor Necrosis Factor (TNF) Alpha Agent in Patients With Hand Osteoarthritis
Condition: Hand Osteoarthritis
MeSH terms: Osteoarthritis
Study type: Interventional
Phase: Phase 3

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): Adalimumab (Humira®); Placebo
Intervention type(s): Other; Other
Intervention description(s): syringes for injections under cutaneous dose = 40mg vol = 0.8 ml; syringes under cutaneous vol = 8 ml
Intervention MeSH terms: Adalimumab
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: Osteoarthritis; Hand; Tumor Necrosis Factor-alpha inhibitors; Biological Therapy