The Use of Rofecoxib (Vioxx) in the Treatment of Hemophilia.
Authors: Rattray Benjamin N. , Nugent Diane J. , Young Guy 
Published: April 2020

BACKGROUND: Joint hemorrhage and subsequent hemophilic arthropathy are significant complications in hemophilia. The pathophysiology of joint damage in such patients involves inflammation and angiogenesis. Cyclooxygenase 2 (COX-2) inhibitors are anti-inflammatory agents approved for use in osteoarthritis and rheumatoid arthritis and have potent anti-inflammatory, anti-angiogenic and analgesic properties yet do not affect platelet function in the manner of traditional NSAIDs. These properties make such agents potentially useful as adjunctive therapy in hemophiliacs. There is only one prior report of rofecoxib treatment in a single hemophiliac patient.

METHODS: A retrospective chart review was conducted of all patients with hemophilia A or B seen at the Children’s Hospital of Orange County and treated with rofecoxib for acute hemarthrosis, chronic synovitis, target joint or pain. The safety and efficacy of rofecoxib treatment was determined based on information gathered from follow-up clinic visits, physical therapy examinations and nursing notes. Efficacy in hemarthrosis was determined by comparing consecutive bleeds treated without and with rofecoxib and judged subjectively as effective, partially effective or ineffective. Efficacy for chronic synovitis and pain was judged subjectively as above. Efficacy in resolution of target joints was judged as effective if the target joint resolved or ineffective if it did not resolve.

RESULTS: A total of 30 patients between 3–40 years of age (26 FVIII deficiency, 4 FIX deficiency, 4 inhibitor patients) were treated for a total of 42 courses of rofecoxib treatment. All courses were evaluated for safety and 31 for efficacy. Rofecoxib was used for 8 acute hemarthroses, 4 target joints, 7 patients with chronic synovitis and 12 episodes of pain (see tables). Dosing regimens were chosen empirically. In most cases patients ≥ 10 years received 25 mg dose and children &lt; 10 years were given 12.5 mg. For pain, patients were treated as needed and for acute hemarthrosis, patients were treated for 5 days. For chronic synovitis, patients were treated daily for 30 days and continued indefinitely if improvement was noted. For target joints, patients were treated until resolution or until no response was noted. A total of 2 bleeding events were noted including a mouth bleed and an episode of hematuria. None of the events led to significant complications and all resolved.

Treatment of acute hemarthrosis with factor alone versus factor and rofecoxib

Efficacy Factor Alone Factor + rofecoxib Ineffective 1 (8%) 0 (0%) Partially Effective 3 (23%) 2 (25%) Effective 9 (69%) 6 (75%)

Efficacy of rofecoxib in the management of target joints (along with factor therapy), chronic arthritis and pain in hemophilia patients

Efficacy Target Joint Chronic Synovitis Pain Note: Efficacy judged subjectively by patient and physicians as ineffective, partially effective or effective. Target joints judged subjectively as ineffective or effective. Ineffective 2 (50%) 0 (0%) 0 (0%) Partially Effective N/A 2 (28.5%) 1 (8%) Effective 2 (50%) 5 (71.5%) 11 (92%)

CONCLUSION: This is the largest study to date evaluating COX-2 inhibitors as adjunctive therapy in hemophilia. This study demonstrates that rofecoxib is safe and resulted in only 2 bleeding events that were mild and not definitively related to the medication. Importantly, it was found to be very effective in the management of chronic synovitis and joint pain. It may be useful as adjunctive therapy in the management of acute hemarthrosis and target joints. Further studies are needed to confirm both safety and efficacy.