Pharmacology Update
Golimumab Injection (Simponi™)
By William T. Elliott, MD, FACP, and James Chan, PharmD, PhD. Dr. Elliott is Chair, Formulary Committee, Northern California Kaiser Permanente; and Assistant Professor of Medicine, University of California, San Francisco. Dr. Chan is Pharmacy Quality and Outcomes Manager, Kaiser Permanente, Oakland, CA. Drs. Elliott and Chan report no financial relationship to this field of study.
A new human monoclonal antibody against tumor necrosis factor (TNF-a) has been approved for the treatment of immune-mediated inflammatory diseases including rheumatoid arthritis. Golimumab is manufactured by Centocor Ortho Biotech Inc, and is marketed as Simponi™.
Indications
Golimumab is indicated for the treatment of adults with moderately to severely active rheumatoid arthritis in combination with methotrexate (MTX), active psoriatic arthritis, and active ankylosing spondylitis with or without methotrexate or other non-biologic disease-modifying antirheumatic drug (DMARD).1
Dosage
The recommended dose is 50 mg given subcutaneously once a month.1 The drug is available as 50 mg/0.5 mL single-dose prefilled autoinjectors and prefilled syringes.
Potential Advantages
Golimumab is given every month, which is less frequently than other anti-TNF-a drugs such as etanercept (Enbrel®) or adalimumab (Humira®), which require twice weekly and every other week dosing, respectively.
Potential Disadvantages
Golimumab has the same boxed warning and standard warnings as other anti-TNF-a drugs. These include the risk of serious infections (bacterial, fungal, viral), malignancies, heart failure, demyelinating disease, concomitant use of other biologics, and live vaccines.1 Common adverse events include upper respiratory infections (7%), injection site reaction (6%), and nasopharyngitis (6%). Antituberculosis treatment should be considered in at-risk patients. Antibodies to golimumab have been reported in 4% of subjects in phase 3 studies. The clinical relevance of this finding is not clear.1
Comments
Golimumab is a human IgG1k monoclonal antibody that binds to both soluble and transmembrane TNF-a. The efficacy of golimumab was shown in 3 studies in rheumatoid arthritis (RA) and one each in psoriatic arthritis (PsA) and ankylosing spondylitis (AS).1-5 The RA studies included subjects 18 years of age and older with moderately to severely active RA according to American College of Rheumatology (ACR) criteria. Subjects also had at least 4 swollen and 4 tender joints. The first study (n = 461) compared two doses of golimumab (50 mg, 100 mg) with placebo. The second study (n = 444) compared two doses of golimumab plus MTX with MTX alone in subjects who had not adequately responded to MTX. The third study (n = 637) compared MTX vs golimumab + MTX in MTX-naïve subjects. Primary endpoint for the first 2 studies was the percent of subjects achieving ACR20 response at week 14 and the primary endpoint for the third study was percent of ACR50 responders at week 24. ACR20 means 20% improvement and ACR50 means 50% improvement in tender joints, swollen joints, and combination of improvement in pain, global assessment, self-addressed disability, and acute-phase reactant (ESR or CRP). No real difference was observed between 50 mg and 100 mg of golimumab. Golimumab monotherapy was similar to MTX. Golimumab 50 mg and MTX was superior to MTX alone (ACR20 response at week 14: 55% vs 33%; at week 24: 60% vs 28%, respectively) in previously treated MTX subjects. In MTX-naïve patients, ACR20 response at week 24 was 62% vs 49% for golimumab and MTX, respectively. Clinical response was seen as early as week 2 and was generally maintained through week 52.3 In the study with PsA (n = 405), golimumab with or without MTX was significantly better than placebo with or without MTX (ACR20 response at week 14: 51% vs 9%). In the AS study (n = 356), golimumab with or without DMARDs (e.g., MTX, sulfasalazine, hydroxychloroquin, low-dose corticosteroid) was significantly more effective than placebo with or without DMARDs. The ASAS20 response at week 14 was 59% vs 22%. ASAS20 represents at least a 20% improvement in 3 of 4 measures of a patient's global assessment, pain, physical functions, and inflammation with no deterioration. The drug is generally well tolerated. There are currently no comparative trials with other anti-TNF-a drugs. However, the magnitude of efficacy is similar to that reported for other studies.6,7
Clinical Implications
Golimumab is the newest anti-TNF-a drug approved for RA, PsA, and AS. It is not known whether golimumab offers any clinical advantage over currently available agents, though it does offer a more convenient dosing regimen (every 4 weeks).
References
1. Simponi Product Information. Horsham, PA: Centocor Ortho Biotech; April 2009.
2. Keystone EC, et al. Golimumab, a human antibody to TNF-{alpha} given by monthly subcutaneous injections, in active rheumatoid arthritis despite methotrexate. Ann Rheum Dis 2008 Dec 11; Epub ahead of print.
3. Kay J, et al. Golimumab in patients with active rheumatoid arthritis despite treatment with methotrexate. Arthritis Rheum 2008;58:964-975.
4. Inman RD, et al. Efficacy and safety of golimumab in patients with ankylosing spondylitis. Arthritis Rheum 2008;5811:3402-3412.
5. Kavanaugh A, et al. Golimumab, a new human tumor necrosis factor alpha antibody, administered every four weeks as a subcutaneous injection in psoriatic arthritis. Arthritis Rheum 2009;60:976-986.
6. Kekow J, et al. Patient-reported outcomes improve with etanercept plus methotrexate in active early rheumatoid arthritis and the improvement is strongly associated with remission. Ann Rheum Dis 2009 Mar 16; Epub ahead of print.
7. Van der Heijde D, et al. Efficacy and safety of adalimumab in patients with ankylosing spondylitis. Arthritis Rheum 2006;54:2136-2146.