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Explore This IssueJanuary 2014
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Pipeline and Drug Approvals
Certolizumab Pegol (Cimzia) has been approved by the U.S. Food and Drug Administration (FDA) for treating adults with active ankylosing spondylitis (AS).1 The FDA also issued a complete response letter for treatment of adults with active axial spondylarthritis (axSpA). This recent FDA approval was based on results of a multicenter, randomized, double-blind, placebo-controlled study in patients with active axSpA. Patients received either certolizumab pegol 200 mg subcutaneously (SubQ) every two weeks, certolizumab pegol 400 mg every four weeks, or placebo. Of 325 patients enrolled, 178 had AS. Primary efficacy was achieving an Ankylosing Spondylitis Response Criteria 20 response at Week 12, and this was met with both statistical and clinical significance in both active-treatment arms compared to placebo-treated patients. Patients who take certolizumab pegol are at an increased risk for development of serious infections, which may lead to hospitalization or death. Most patients who have developed these infections were also taking immunosuppressants, such as corticosteroids or methotrexate. Certolizumab pegol should be stopped if a serious infection or sepsis arises.
Methotrexate (MTX; Otrexup) has been FDA approved in a disposable, automatic injection device for once-weekly SubQ administration.2 The device is to be used by adults with severe rheumatoid arthritis (RA) who have not had an adequate response to full-dose nonsteroidal antiinflammatory agents, adults with psoriasis, or children with polyarticular juvenile idiopathic arthritis.
Sarilumab is a fully human monoclonal antibody directed against the interleukin 6 (IL-6) receptor that is currently in phase III clinical trials.3 It is administered SubQ. In the 52-week SARIL-RA-MOBILITY trial, 1,200 patients received either sarilumab 200 mg, or 150 mg, or a matched placebo every other week, along with MTX. Treated patients had active RA and were inadequate responders to MTX. Sarilumab-treated patients had statistically significant and clinically relevant improvements in all three coprimary endpoints compared to placebo-treated patients (P<0.0001). The three endpoints were: 1) improvement in signs and symptoms of RA at Week 24, measured by the ACR20; 2) physical function improvement, measured from baseline to Week 16 using the Health Assessment Questionnaire–Disability Index; and 3) Structural damage progression inhibition at Week 52, measured by the change in modified Van der Heijde total Sharp Score. The ACR50 and 70 at Week 24 were also statistically significant for the sarilumab-treated groups, compared with the placebo-treated groups. Infections were the most common adverse effect and occurred more frequently in the active-treatment groups compared with the placebo-treated group. In the sarilumab-treated patients, there was a dose-dependent decrease in mean neutrophil counts. Transaminase and mean LDL cholesterol increases were also seen.
Tocilizumab (Actemra), which targets the IL-6 receptor, has been FDA approved as a SubQ formulation for adults with RA who have not fully responded to treatment with conventional disease-modifying antirheumatic drugs (DMARDs).4 Approval was based on two randomized trials. The SUMMACTA trial (n=1,262) was six months in duration and compared the intravenous (IV) formulation of tocilizumab to the SubQ formulation in patients with moderate to severe RA. This noninferiority trial compared the ACR20 response at Month 6 between 8 mg/kg of IV tocilizumab every month and 162 mg of weekly SubQ tocilizumab. Patients were also receiving conventional DMARDs. Comparable efficacy was obtained with a 69% response in the SubQ-treated group and a 73% response in the IV-treated group. The BREVACTA trial (n=656) compared SubQ tocilizumab every two weeks to placebo. Tocilizumab-treated patients had a 61% response rate compared with placebo-treated patients (32%), as well as significantly less joint damage. Injection-site reactions were more common with the SubQ formulation, otherwise the safety profiles of the two formulations were similar.
The FDA is to phasing out prescription opioid products that are combined with more than 325 mg of acetaminophen, in an attempt to decrease the amount of hepatotoxicity associated with their use. This phaseout begins January 14, 2014.5 Prior to this date, any combination product with more than 325 mg of acetaminophen could exist. Some of these products included generic hydrocodone/acetaminophen combinations (or their brands, Zydone, Vicodin, Vicodin ES, Vicodin HP, Lortab); generic oxycodone/acetaminophen combinations (or their brands, Percocet, Roxicet 5/500, Tylox); and butalbital combinations. After January 14, 2014, the maximum amount of acetaminophen allowable in these products will be 325 mg. Rather than reformulating all products to 325 mg of acetaminophen, the Vicodin-brand products were already reformulated to contain less than 325 mg of acetaminophen. Since most combination products will have 325 mg of acetaminophen, having these products with 300 mg acetaminophen will likely be confusing for many. For patients requiring a combination of acetaminophen and hydrocodone, write prescriptions for generic products with 325 mg as the amount of acetaminophen. This will cause less confusion and will give the pharmacist a number of options with which to choose to fill the prescription.
Dr. Kaufman is a freelance medical writer based in New York City, a pharmacist at New York Presbyterian–Lower Manhattan Hospital, and adjunct faculty at Touro College of Pharmacy.
- Cimzia (certolizumab pegol) approved by FDA for treatment of adults with active ankylosing spondylitis. Published October 18, 2013. Available at www.firstwordpharma.com/print/1147509?tsid=17. Accessed November 26, 2013.
- Dearment A. Sanofi and Regeneron report positive results with sarilumab in first phase 3 rheumatoid arthritis registration trial. Published October 14, 2013. Available at http:// http://newsroom.regeneron.com/releasedetail.cfm?ReleaseID=809088. Accessed December 9, 2013.
- FDA approves easy-to-use injectable methotrexate for RA, psoriasis, juvenile arthritis Published November 22, 2013 http://www.drugstorenews.com/article/fda-approves-easy-use-injectable-methotrexate-ra-psoriasis-juvenile-arthritis Accessed November 26, 2013.
- Walsh N. FDA greenlights sub Q Actemra. Published October 22, 2013. Available at www.medpagetoday.com/Rheumatology/Arthritis/42414. Accessed November 25, 2013.
- Opioids. Pharmacist’s Letter: 2013;29(12).