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.
