Specialty Pharmaceuticals--Therapy Class Review: Rheumatoid Arthritis

Mr. Allinson is chief executive officer and chief clinical officer of Therigy, LLC.

Rheumatoid arthritis (RA) is a chronic and progressive autoimmune disease. Because RA is a systemic condition, it is distinguished from other forms of arthritis by the symmetrical pattern it exhibits (ie, affecting joints on both sides of the body). In addition to affecting the joints, the disease process associated with RA may affect other organs such as the skin, eyes, lungs, heart, blood, nerves, or kidneys. In joints, the inflammation caused by RA triggers the classic symptoms of pain, stiffness, and swelling, which can lead to permanent damage. Because no cure currently exists for RA, a great importance is placed on starting effective treatment as soon as possible to delay or prevent joint damage and permanent loss of movement.

Economic Impact

• Arthritis and related conditions cost the US economy nearly $49 billion (inflated from 1998) per year in direct medical care and indirect costs, including lost wages and productivity.¹

- On a patient level, annual costs for the treatment of RA have been reported to be about $8500 (inflated from $2000).²

• RA results in more than 9 million physician visits and more than 250,000 hospitalizations per year in the United States.^2,3

- The average number of days absent from work due to RA was reported to range from 2.7 to 30 days per year.²

• It has been reported that one quarter of patients will require surgery (often involving total joint replacement) within 10 years of disease onset.⁴

- Direct costs for total hip arthroplasty services in the United States are about $12,8465; costs for total knee arthroplasty are about $20,700.⁶

Demographic/Prevalence Data

• RA is the most common systemic inflammatory arthritis seen in primary care and affects 2.1 million Americans—about 0.5% to 1% of the adult US population.⁷

• The average age of an individual with RA is 66 years; onset occurs usually in middle-age, but also presents in the 20s and 30s. ⁷

• The prevalence of RA is about twice as high in women than men, with incidence 2 to 3 times higher in women than in men.⁷

Pharmacologic Treatment

Historically, pharmacologic treatment of RA has been geared toward the treatment of symptoms (eg, pain and inflammation) and starts with corticosteroids/ nonsteroidal anti-inflammatory drugs. As treatment progresses, 1 or more (and often in combination) disease-modifying antirheumatic drugs (DMARDs) are used, although side effects and adverse events can limit their use, and patients are carefully monitored when using these agents (see the Table for current therapies). Though anti-inflammatory drugs and DMARDs have a role in the treatment of RA, none of them have the ability to prevent underlying disease progression and disability.

The introduction of a series of monoclonal antibodies (biologic response modifiers [BRMs]) to treat RA has changed this situation dramatically. A real likelihood now exists of changing the progression of this chronic disease, decreasing disability levels, and enabling a better lifestyle for RA patients.

These BRMs, such as the anti—tumor necrosis factor (TNF)-alpha products (or TNF inhibitors), target early pathways of inflammation, thereby stopping the cycle that leads to tissue and joint destruction. All of these currently marketed products have had great clinical success.

Looking ahead, the next wave of novel RA therapies will be dependent on their ability to address the key issues of cost-effectiveness, ease of administration, and continued positive clinical outcomes. Certolizumab pegol (Cimzia) and golimumab (Simponi), the 2 newest TNF inhibitors, were recently approved by the FDA and may address these issues. Both require less frequent administration than earlier therapies. As the patient population for TNF inhibitor use is reaching a pinnacle, focus is shifting to patients who failed anti-TNF therapy and the development of products other than TNF inhibitors. In the pipeline, an interleukin (IL)-6 inhibitor, tocilizumab (Actemra), and fully humanized CD20 antibodies, ofatumumab (Arzerra), may have the greatest potential.

The closely watched race between Roche/Genentech/ Biogen Idec and Genmab/GlaxoSmithKline to launch their fully humanized CD20 monoclonal antibodies may impact the use of the currently marketed product, rituximab (Rituxan), especially because preliminary clinical trial data suggest that they could have a lower side effect profile and be more efficacious.