New drugs: Golimumab, besifloxacin hydrochloride, and artemether/lumefantrine

Antiarthritic agent Golimumab (Simponi—Centocor Ortho Biotech) is the fifth tumor necrosis factor (TNF) blocker (inhibitor) to be marketed for the treatment of rheumatoid arthritis, joining etanercept (Enbrel), infliximab (Remicade), adalimumab (Humira), and certolizumab pegol (Cimzia). The latter agent was initially marketed in 2008 for the treatment of Crohn’s disease and was subsequently approved in May 2009 for the treatment of rheumatoid arthritis. Golimumab is a humanized monoclonal antibody that prevents the binding of TNF alpha to its receptors, thereby inhibiting its activity. Like etanercept, adalimumab, and certolizumab, golimumab is administered subcutaneously, whereas infliximab is administered intravenously. The new drug is specifically indicated for use in adult patients for the treatment of moderately to severely active rheumatoid arthritis (in combination with methotrexate), active psoriatic arthritis (alone or in combination with methotrexate), and active ankylosing spondylitis. Etanercept, adalimumab, and infliximab are also indicated for the three conditions for which golimumab has been approved, although the specifics of these indications vary in some instances. For example, in the treatment of rheumatoid arthritis, the indication for golimumab and infliximab involves use in combination with methotrexate, whereas such combination use is not required with etanercept and adalimumab (or certolizumab). The labeled indications for etanercept and adalimumab in the treatment of rheumatoid arthritis also reflect the benefits of inducing major clinical response, inhibiting the progression of structural damage, and improving physical function, and the latter two are included in the labeled indication for infliximab. In the treatment of psoriatic arthritis, the labeled indication for etanercept, adalimumab, and infliximab, but not for golimumab, includes reference to inhibiting the progression of structural damage and improving physical function. The effectiveness of golimumab in the treatment of rheumatoid arthritis was demonstrated in three controlled trials. One of these studies included patients who had been previously treated with one or more doses of another TNF blocker without a serious adverse event but who had discontinued this treatment for a variety of reasons. In all three studies, a higher percentage of patients who were treated with the combination of golimumab and methotrexate experienced improvement at the week 14 and 24 evaluation points compared with patients treated with methotrexate alone. Golimumab has not been directly compared with other TNF blockers in clinical studies, and data are not sufficient to conclude that it is effective in patients in whom response with other TNF blockers has been inadequate. In patients with psoriatic arthritis or ankylosing spondylitis, the use of golimumab resulted in significant improvement in signs and symptoms. Including methotrexate in the regimen for treating psoriatic arthritis did not provide a consistent benefit, and golimumab may be used alone or in combination with methotrexate in the treatment of this disorder. Certain of the TNF blockers have also been approved for other indications. Etanercept and adalimumab are indicated for the treatment of juvenile idiopathic arthritis, and these agents, as well as infliximab, are indicated for the treatment of plaque psoriasis. Infliximab, adalimumab, and certolizumab are indicated for the treatment of patients with Crohn’s disease, and infliximab is also indicated for the treatment of patients with ulcerative colitis. However, these are not labeled indications for golimumab currently. The risks and adverse events associated with the use of golimumab are generally similar to those of the other TNF blockers. Of greatest concern is the potential for serious infection (e.g., tuberculosis [TB], invasive fungal infections, other opportunistic infections), some of which have been fatal and which are the subject of a boxed warning in the product labeling. Treatment with golimumab should not be initiated in patients with an active infection, including clinically important localized infection. Patients should be evaluated for TB risk factors and tested for latent TB infection. A risk of reactivation of hepatitis B virus in patients who are chronic carriers of this virus also exists. The risk of serious infections is increased if a TNF blocker is used concomitantly with abatacept (Orencia) or anakinra (Kineret). Accordingly, golimumab should not be used concurrently with one of these agents. The TNF blockers have also been associated with a risk of malignancies (e.g., lymphomas). The risks and benefits of golimumab should be carefully evaluated before initiating treatment in a patient with a known malignancy or when considering whether to continue treatment in a patient who develops a malignancy. Other risks with the use of golimumab, as well as the other TNF blockers, include exacerbation or new onset of congestive heart failure, exacerbation or new onset of central nervous system demyelinating disorders (e.g., multiple sclerosis), and hematologic reactions