New Approvals
- Ketorolac tromethamine intranasal (Sprix) has been approved by the U.S. Food and Drug Administration (FDA).1 Nasal ketorolac, a nonsteroidal antiinflammatory drug (NSAID), is approved for short-term (up to five days) treatment of acute moderate to moderately severe pain requiring opioid-level analgesia. Gastrointestinal hemorrhage, bleeding, and cardiovascular risks are included in the labeling. Mild, transient nasal discomfort was the most common adverse reaction in clinical trials.
Pipeline
- Belimumab (Benlysta), an investigational agent currently in phase III trials, did not show statistical significance in relation to the difference in response rates at Week 76 in seropositive patients with systemic lupus erythematosus (SLE) taking the drug compared with those who received placebo.2 In the BLISS-76 study, 819 patients with serologically active SLE were enrolled. They were randomized to receive standard of care and placebo or one of two belimumab doses for 76 weeks. At Week 52, 43.2% of high-dose belimumab-treated patients had significant symptom improvement versus 34% of placebo-treated patients. At Week 76, 38.5% of patients responded to high-dose belimumab versus 32.4% of placebo-treated patients.
- Naproxcinod was evaluated in mid-May as an antiinflammatory agent to treat symptoms of osteoarthritis (OA).3 Its manufacturer stated that it has similar safety and efficacy to naproxen but that it does not have some of the same cardiovascular complications, such as blood pressure increases, associated with other NSAIDs. This is because it is metabolized to yield naproxen and a nitric oxide-donating moiety, which is believed to play an important role in controlling blood pressure. Naproxcinod appears to be safe and effective for treating OA, but its cardiovascular risks are not clear. The FDA evaluation did not conclusively show that the submitted data supports the claim of cardiovascular benefit. A final FDA decision is due by July 23.
- Ocrelizumab, a humanized anti-CD20 monoclonal antibody which was in late-phase clinical trials to treat lupus and rheumatoid arthritis (RA), has been suspended due to safety concerns.4 Four RA clinical trials were evaluated by a safety monitoring board in March and some serious infections in clinical trials were noted, some leading to death. The developer decided that the overall benefit-to-risk profile was not favorable, considering other agents that are currently part of the RA armamentarium. The lupus trials were discontinued in March.5
- Oxycodone/niacin (Acurox) was filed for FDA approval and evaluated by an FDA advisory panel in late April for the treatment of moderate to severe pain while acting as a misuse and abuse deterrent. The panel voted 19 to one against approving the agent. There were concerns related to the abuse-deterrent properties of immediate-release oxycodone and whether the addition of niacin was enough to deter abuse of the agent.6 The agent was developed to aggravate nasal passages if inhaled and to form a gel when dissolved in water to make it difficult to take intravenously. The company is working with the FDA to determine the next steps for this product.
Safety
The FDA has updated the warning section of the product labeling for tramadol and tramadol/acetaminophen.7,8 This warning accentuates the risk of suicide in patients who are addiction prone and those who are also taking tranquilizers or antidepressant drugs. In addition, it warns of an overdose risk when the recommended dose is exceeded or when it is used in combination with central nervous system (CNS)–active drugs or alcohol. Tramadol-related deaths have occurred in patients with previous histories of emotional disturbances or suicidal ideation or suicide attempts, as well as in patients with a history of misuse of alcohol, tranquilizers, and other CNS-active drugs. Tramadol may produce additive effects when used with these agents, in conjunction with alcohol or with other opioids or illicit drugs that cause CNS depression. Consequences of tramadol overdose include CNS depression, respiratory depression, and death. Tramadol has mu-opioid agonist activity, is often abused, and may be subject to criminal diversion.
Biologics for Pediatric Patients with Juvenile Idiopathic Arthritis
Juvenile idiopathic arthritis (JIA) is a chronic, debilitating autoimmune musculoskeletal disease in children with onset prior to age 16.9 More than 50% of children who have this disease become adults with active disease. Therefore, the changing treatment paradigm is early aggressive combinations of agents to achieve disease remission. Therapy goals include allowing normal childhood activities, growth, and development, eliminating active disease, and normalizing joint function while limiting permanent disability by preventing long-term joint damage or blindness from chronic uveitis.9,10
