The introduction of TNFα inhibitors such as Enbrel, Remicade and Humira, has transformed the treatment of inflammation in autoimmune and rheumatic diseases including rheumatoid arthritis, psoriasis, psoriatic arthritis, ulcerative colitis, and anklyosing spondylitis. Due to the significant improvement over older drugs, the market for biologics in autoimmune diseases has grown to over $16B in the United States, Europe, and Japan. Because these drugs can work differently in each patient, the current market supports three large competitors selling over $4B each.
Image: Damage in a patient with Rheumatoid Arthritis
Despite the success of these therapies relative to older drugs, they do not cure disease nor do they provide sufficient relief of disease in many patients. For example Enbrel, the most effective agent, provides effective relief (75% reduction in symptoms) in only 22% of patients with rheumatoid arthritis at 12 months. When combined with the older chemotherapy drug methotrexate, this relief is seen in 40% of patients. The efficacy of these agents diminishes over time.
Image: Damage in a patient with Psoriasis
For the 22-40% of patients who could get relief, the side effects of this class of drugs may prevent them from accessing therapy. These include the increased risk of tuberculosis, gram positive infections, and lymphomas. It is now clear that there is increased risk of serious infections in patients treated with anti-TNFα therapies due to suppression of the innate immune system. Other complications such as the development of lupus-like disease, demyelinating disease, lymphomas, and worsening of heart failure are contrary to the concept of reducing TNFα activity.
Despite the success of TNFα inhibitors, the majority of patients with rheumatic diseases need alternatives that are more effective and safer.
Sources: IMS 2009; Enbrel Prescribing Information 2008
