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

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 >4 or morning stiffness of >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 >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 17women; 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 >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.

Association between the use of serotonin receptor 2A–blocking antidepressants and joint disorders

“…However, there are certain drugs or groups of drugs that have been shown in clinical studies to be connected with ADRs in the joints, e.g., bisphosphonates (1,2).…”

Bisphosphonates: Environmental protection for the joint?

“…In fact, there is evidence that, in some instances, these agents may reduce inflammation. The reduction in systemic signs of inflammation has been particularly dramatic in patients with ankylosing spondylitis (AS) (30)(31)(32)(33). For example, in a recent trial, investigators demonstrated that 6 months of therapy with pamidronate resulted in improved clinical, laboratory, and radiologic parameters of disease activity (30).…”

“…The reduction in systemic signs of inflammation has been particularly dramatic in patients with ankylosing spondylitis (AS) (30)(31)(32)(33). For example, in a recent trial, investigators demonstrated that 6 months of therapy with pamidronate resulted in improved clinical, laboratory, and radiologic parameters of disease activity (30). High doses of pamidronate were used in that study, which may have resulted in unique effects on immune or inflammatory cell function that may be distinct from the effects on osteoclasts or other bone cell types.…”

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: Comment on the article by Maksymowych et al

“…We read with great interest the article by Maksymowych et al (1). The only complication associated with pamidronate therapy in their study was transient arthralgias/ myalgias after the first intravenous (IV) infusion.…”