Clinical Trial: Infliximab Therapy in Patients With Refractory Polymyalgia Rheumatica

Study Status: Completed
Recruit Status: Unknown status
Study Type: Interventional

Official Title: Infliximab Therapy in Patients With Refractory Polymyalgia Rheumatica: a Double Blind Placebo Controlled Trial

Brief Summary:

Rheumatic Polymyalgia(PMR) is a relatively common chronic inflammatory disorder of unknown origin which predominantly develops in elderly subjects and presents with severe pain and stiffness in the neck, shoulder and pelvic girdles, along with increased acute phase reactants. Systemic manifestations such as fever, anorexia and weight loss are characteristic signatures of PMR.

Corticosteroids (CS) constitute the standard treatment of PMR. Although in most patients the symptoms of the disease disappear after one or two years of treatment, a proportion of patients remain CS-dependent with the subsequent CS toxicity. Open label studies have suggested that tumour necrosis factor (TNF) antagonists lead to sustained improvement and CS sparing effect in patients with refractory PMR.

The investigators conducted a randomised, double-blind, placebo controlled trial with infliximab in CS-dependent patients with PMR. Patients with CS-dependent PMR (defined as requiring ≥ 5 mg/day after at least 2 years of treatment to maintain remission or ≥ 7.5 mg/day after at least 6 months) were randomly assigned to receive Infliximab (5 mg/kg i.v) at 0, 2, 6, 14 and 22 weeks (n = 12) or placebo (n = 11) together with CS that were reduced according to a predefined schedule. The primary outcome was the proportion of responder patients -defined as individuals with both complete clinical and analytical remission without receiving CS for at least three months- at 24 weeks. Secondary outcomes were cumulative CS doses and adverse events proportion.


Detailed Summary:

The duration of the study will be 1 year, and it will be divided in several phases:

A) Initial phase (double-blind trial): Between week 0 and week 24. Placebo or Infliximab at a dose of 3 mg/kg/day at weeks 0, 2 and 6.

After the screening process, patients who meet the inclusion/exclusion criteria of the protocol will be randomized to receive three infusions of placebo or infliximab as previously described.

After the first infusion (week 0), the prednisone dose will be tapered according to the following schedule: Prednisone (or equivalent) should be decreased at a rate of 1.25 mg per week until complete withdrawal of corticosteroids. In case of relapse, the dose of prednisone will be increased up to the previous dose that controlled the symptoms of PMR, and after 4 weeks of stable dose, prednisone will be again tapered but with a slower schedule: 1.25 mg every 2 weeks until complete withdrawal of corticosteroids. In case of a new relapse, the dose of prednisone will be managed according to the physician criteria.

B) Extension phase (open trial): Between week 24 and week 48. Infliximab at a dose of 3 mg/kg/day at weeks 24, 26 and 30.

At 24 weeks, all the patients included into the trial and still on corticosteroid therapy with or without clinical manifestations of PMR, will receive three infusions of infliximab according to the previous described schedule.

After the first infusion (week 24) the dose of prednisone will be decreased according to the same schedule previously described in the initial phase of the trial.

The schedule therapy proposed in the extension phase is going t
Sponsor: Hospital Universitario Marqués de Valdecilla

Current Primary Outcome: Proportion of responders(complete remission without corticosteroids) [ Time Frame: at 24 weeks ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Proportion of responders [ Time Frame: at 48 weeks ]
  • Time to response [ Time Frame: 48 weeks ]
  • Number of relapses / recurrences [ Time Frame: 48 weeks ]
  • Response duration [ Time Frame: 48 weeks ]
  • Cumulative dose and side effects of steroids [ Time Frame: at 24 and 48 weeks ]
  • Number of patients that should be re-treated with infliximab [ Time Frame: 48 weeks ]
  • Side effects of Infliximab in this patient population [ Time Frame: 48 weeks ]


Original Secondary Outcome: Same as current

Information By: Hospital Universitario Marqués de Valdecilla

Dates:
Date Received: July 19, 2011
Date Started: June 2007
Date Completion: December 2011
Last Updated: August 25, 2011
Last Verified: August 2011