A six-month randomized, controlled, double-blind, dose-response comparison of intravenous pamidronate (60 mg versus 10 mg) in the treatment of nonsteroidal antiinflammatory drug-refractory ankylosing spondylitis

Arthritis Rheum. 2002 Mar;46(3):766-73. doi: 10.1002/art.10139.

Abstract

Objective: To determine the safety and efficacy of intravenous (IV) pamidronate treatment in ankylosing spondylitis (AS) patients who have had a suboptimal response to nonsteroidal antiinflammatory drugs (NSAIDs).

Methods: Pamidronate at 60 mg was compared with pamidronate at 10 mg rather than placebo in view of the high incidence of transient arthralgias upon first IV exposure to the drug. The drug were given monthly for 6 months in a randomized double-blind, controlled trial. The inclusion criterion was active disease (Bath AS Disease Activity Index [BASDAI] of > or = 4 or morning stiffness of > or = 45 minutes) despite stable NSAID therapy. The primary outcome measure was the BASDAI, and secondary outcomes included the Bath AS Functional Index (BASFI), Bath AS Global Index (BASGI), Bath AS Metrology Index (BASMI), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) level, and percentage of patients achieving a reduction of > or = 25% in the BASDAI. Outcome assessments were done at -2, 0, 12, and 24 weeks, and analysis was by intent to treat.

Results: Eighty-four AS patients (67 men and 17 women; mean age 39.6 years and mean disease duration 15.1 years) were enrolled. Dosage groups were well matched at baseline for demographics, disease activity, and functional indices. At 6 months, the mean BASDAI had decreased by 2.22 (34.5%) in the 60-mg group and by 0.93 (15%) in the 10-mg group (P = 0.002). Significantly greater reductions in the 60-mg group were also noted for the BASFI (P < 0.001), BASGI (P = 0.01), and BASMI (P = 0.03). Significantly more patients achieved a reduction of > or = 25% in the BASDAI in the 60-mg group versus the 10-mg group (63.4% versus 30.2%; P = 0.004). Differences in ESR/CRP were not significant (NS). Withdrawals included 9 (20.9%) from the 10-mg group and 3 (7.3%) from the 60-mg group (P NS). Adverse events were confined to transient arthralgias/myalgias after the first IV infusion, occurring in 68.3% and 46.5% of patients in the 60-mg and 10-mg groups, respectively (P NS).

Conclusion: Pamidronate has dose-dependent therapeutic properties in AS.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-Inflammatory Agents / administration & dosage*
  • Anti-Inflammatory Agents / adverse effects
  • Anti-Inflammatory Agents / therapeutic use
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Arthralgia / chemically induced
  • Diphosphonates / administration & dosage*
  • Diphosphonates / adverse effects
  • Diphosphonates / therapeutic use
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Female
  • Humans
  • Injections, Intravenous
  • Male
  • Middle Aged
  • Muscular Diseases / chemically induced
  • Pain / chemically induced
  • Pamidronate
  • Retreatment
  • Severity of Illness Index
  • Spondylitis, Ankylosing / drug therapy*
  • Spondylitis, Ankylosing / physiopathology

Substances

  • Anti-Inflammatory Agents
  • Anti-Inflammatory Agents, Non-Steroidal
  • Diphosphonates
  • Pamidronate