Methylprednisolone acetate (Pfizer’s Depo-Medrol, generics) is the 6-methyl derivative of the corticosteroid prednisolone. Methylprednisolone acetate is indicated for a number of arthritic disorders as well as other inflammatory conditions such as asthma. Similar to other corticosteroids, methylprednisolone acetate inhibits the synthesis of proinflammatory mediators (prostaglandins, leukotrienes, and cytokines), the expression of COX-2, and the activity of collagenase and other cartilage-damaging enzymes. Because of the lack of large-scale, placebo-controlled trials comparing methylprednisolone acetate with placebo in rheumatoid arthritis patients, this section presents the findings of a blinded study involving 18 knees of 16 patients with rheumatoid arthritis or other arthritic conditions (e.g., psoriatic arthritis, juvenile rheumatoid arthritis). In this study, patients underwent …
[ Continue Reading... ]Category: Arthritis
Overview As a result of the GI side effects that occur with traditional NSAIDs, considerable effort has been expended in developing new agents with less GI toxicity. In 1991, researchers achieved a major breakthrough when they discovered that two distinct isoforms of COX exist. COX-1, or constitutive cyclooxygenase, is present in cells under normal physiological conditions and stimulates the synthesis of prostaglandins that help regulate renal function, blood flow, and platelet activity and help protect the mucous membrane along the GI tract. COX-2, or inducible cyclooxygenase, is expressed only under pathological conditions. Its production is induced by proinflammatory cytokines, mitogens, or endotoxins, and it stimulates the production of prostaglandins …
[ Continue Reading... ]Celecoxib (Pfizer/Astellas’s Celebrex) received FDA approval for the treatment of OA and rheumatoid arthritis in December 1998 and was launched in Europe in 2000. Pfizer markets this agent in all the countries under study except Japan, where Astellas Pharma (formerly Yamanouchi Pharmaceuticals, which merged with Fujisawa Pharmaceuticals on April 1, 2005, to form Astellas Pharma) is guiding it through clinical development. A new drug application (NDA) for pain and other symptoms of rheumatoid arthritis and OA was submitted in Japan in December 2002, with approval expected in 2004, but the application was still under consideration at the time of the writing of this report. Celecoxib gained FDA approval for the management …
[ Continue Reading... ]In April 2002, Pfizer launched the first second-generation selective COX-2 inhibitor, valdecoxib (Bextra), in the United States for the treatment of OA, rheumatoid arthritis, and dysmenorrhea. In May 2003, valdecoxib received approval in Europe for treatment of the pain and inflammation associated with OA, rheumatoid arthritis, and primary dysmenorrhea and has since launched in the United Kingdom, Germany, and Italy. As of this writing, sales of valdecoxib remain suspended. In vitro studies by Pfizer showed valdecoxib to be the most potent and selective of the marketed COX-2 inhibitors, providing a basis for the observed potent analgesic and anti-inflammatory activity of the agent in humans. Valdecoxib works by the same mechanism of …
[ Continue Reading... ]Merck’s second-generation COX-2 inhibitor, etoricoxib (Arcoxia), was approved in the United Kingdom in April 2002 for the treatment of symptomatic pain relief in OA, rheumatoid arthritis, acute gouty arthritis, chronic musculoskeletal pain, acute pain associated with dental surgery, and primary dysmenorrhea. By October 2002, etoricoxib had been approved in Europe under the Mutual Recognition Procedure, and it has since launched in Italy and Spain. The U.K. launch came on the heels of the company’s withdrawal of its initial NDA for approval in the United States, following the FDA’s request for additional data on etoricoxib’s cardiovascular safety. In December 2003, Merck submitted an expanded NDA, seeking indications for the treatment of OA, …
[ Continue Reading... ]Overview Generally, the first course of therapy for rheumatoid arthritis initiated by primary care physicians has been nonsteroidal anti-inflammatory drugs (NSAIDs), which are mainly administered to help relieve pain and inflammation. Their analgesic effect is felt quickly and lasts just a few hours, whereas their anti-inflammatory properties become apparent only after several days of repeated administration. However, NSAIDs are unable to halt the progression of rheumatoid arthritis or prevent joint damage caused by the disease. This symptomatic treatment approach covers the use of both older NSAIDs and the more recently introduced selective (COX-2) inhibitors. The older NSAIDs are often referred to as nonselective relative to the highly …
[ Continue Reading... ]Naproxen (Roche’s Naprosyn/Anaprox/Proxen, Bayer’s Aleve, generics), a naphthaleneacetic acid derivative, is a long-acting traditional NSAID available OTC and by prescription. The OTC preparations of this drug are all sodium salts (naproxen sodium), but prescription formulations are either naproxen (Naprosyn) or naproxen sodium (Anaprox). The sodium salt was developed to enable faster drug dissolution, thus speeding absorption and onset of action. A controlled-release formulation of naproxen sodium (Wyeth/Elan’s Naprelan, generics) is also available. Like other traditional NSAIDs, naproxen inhibits the activity of the COX enzymes, thereby preventing the production of prostaglandins. By inhibiting prostaglandin production, naproxen is able to reduce pain and inflammation. In a placebo-controlled, double-blind study, 1,149 rheumatoid arthritis patients …
[ Continue Reading... ]Meloxicam (Boehringer Ingelheim/Abbott/Daiichi’s Mobic) has been available in Europe since 1996. It was approved and launched in mid 2000 in the United States for osteoarthritis (OA), where it is co-promoted by Boehringer Ingelheim and Abbott. In July 2004, the FDA expanded meloxicam’s label by approving the drug to treat signs and symptoms of rheumatoid arthritis. The drug launched in Japan in February 2001, and was comarketed by Nippon Boehringer Ingelheim and Daiichi Pharmaceutical. However, Daiichi took over full Japanese marketing rights for meloxicam in May 2004. Meloxicam lost European patent protection at the end of 2003 and U.S. patent protection in 2005; the Japanese patent for meloxicam has already expired. Meloxicam …
[ Continue Reading... ]Launched in 1998 in the United States, etanercept (Amgen/ Wyeth/Takeda’ s Enbrel) was the first tumor necrosis factor-alpha inhibitor approved for the treatment of rheumatoid arthritis. It was initially indicated for moderate to severe rheumatoid arthritis patients unresponsive to one or more conventional Disease-modifying antirheumatic drugs or for use in combination with methotrex-ate for patients unresponsive to methotrexate alone. It has since been granted orphan drug approval for use in juvenile rheumatoid arthritis patients. In June 2000, the FDA expanded the agent’s label to include reducing symptoms and delaying structural damage in patients with moderate to severe, active rheumatoid arthritis at an early stage. In July 2003, the FDA approved a …
[ Continue Reading... ]Infliximab (Centocor [a subsidiary of Johnson&Johnson]/Schering-Plough/Tanabe Seiyaku’s Remicade) was the second tumor necrosis factor-alpha inhibitor to make a major impact on the treatment of rheumatoid arthritis. It is marketed in the United States by the originator, Centocor; by licensee Schering-Plough in Europe; and by Tanabe Seiyaku in Japan, where it has been the only tumor necrosis factor-alpha inhibitor available until the 2005 launch of etanercept. Initially launched in the United States in 1998 for the short-term treatment of Crohn’s disease, infliximab received FDA approval in 1999 for use in combination with methotrexate to treat adult rheumatoid arthritis patients refractory to methotrexate alone. In December 2000, labeling was expanded for use of …
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