Golimumab

Simponi (Schering-Plough)
prefilled syringe or autoinjector containing 50 mg in 0.5 mL
Approved indications: rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis
Australian Medicines Handbook section 15.2.1

Treatment with tumour necrosis factor inhibitors improves the signs and symptoms of severe autoimmune inflammatory joint diseases. Golimumab is a recombinant human monoclonal antibody that binds to tumour necrosis factor alpha, blocking its activity. It has been approved for several indications in Australia including:

• rheumatoid arthritis, in combination with methotrexate when other treatments have failed
• psoriatic arthritis, alone or in combination with methotrexate when other treatments have failed
• ankylosing spondylitis in adults.

Following subcutaneous injection, maximum serum concentrations of golimumab are reached within two to six days. Steady-state serum concentrations are reached after 12 weeks following monthly injections of golimumab 50 mg. The mean terminal half-life ranges from 11 to 14 days. The clearance of golimumab is increased in patients with antigolimumab antibodies, but it is unclear what effect these antibodies have on safety and efficacy. Treatment with concurrent methotrexate reduces the number of patients who develop antibodies.

The efficacy of golimumab for moderate to severe active rheumatoid arthritis has been shown in three placebo-controlled trials totalling 1542 patients. ^1,2 Patients in the trials had at least four swollen or tender joints. Golimumab 50 mg or 100 mg, or placebo, was given subcutaneously with or without methotrexate every four weeks. Response to treatment was measured according to the American College of Rheumatology 20% improvement (ACR20) or 50% improvement (ACR50) criteria. These are composite outcomes that assess the number of swollen and tender joints, the erythrocyte sedimentation rate or C-reactive protein concentration and global assessments of arthritis activity by the patient and doctor.

In the GO-FORWARD trial (444 patients), over half of the patients receiving golimumab plus methotrexate (55.1% with 50 mg and 56.2% with 100 mg) had a 20% improvement in symptoms by week 14, versus only a third receiving placebo plus methotrexate. Patients receiving golimumab with methotrexate also reported improvements in their physical function after 24 weeks. There were 12 serious infections during the trial 11/311 patients receiving golimumab and 1/133 patients receiving placebo. One of the patients who had received two doses of golimumab 100 mg died from sepsis after developing pneumonia. None of the 92 patients who were being treated for latent tuberculosis (usually isoniazid) at baseline developed active infection during the trial. Three patients receiving the study drug had malignancies these were squamous cell cancer, basal cell cancer and breast cancer. ¹

The GO-AFTER trial enrolled 461 patients who had previously used tumour necrosis factor inhibitors. They were allowed to continue methotrexate, sulfasalazine or hydroxychloroquine. After 14 weeks, significantly more patients had responded to golimumab than to placebo (ACR20: 35% with 50 mg and 38% with 100 mg vs 18% with placebo). Two patients receiving the study drug developed cancer one was squamous cell carcinoma and the other was lymphoma. There were six serious infections with golimumab (pneumonia, bronchitis, upper respiratory tract infection, urinary tract infection, urosepsis). ²

In the GO-BEFORE trial, which enrolled 637 patients who had not previously received methotrexate, the primary end point was not met. However, in a post hoc modified intention-to treat analysis, more patients receiving golimumab plus methotrexate had a 50% improvement in their symptoms by week 24, compared to those receiving placebo plus methotrexate (ACR50: 40.5% with 50 mg and 36.5% with 100 mg vs 29.4% with placebo). Unexpectedly, only the response rate to the lower golimumab dose was significantly better than placebo. The response of patients who received golimumab alone without methotrexate was not that different to those given placebo plus methotrexate (ACR50: 33.1% vs 29.4%). ³

Nausea was the most common adverse event with golimumab plus methotrexate (13.9-15.1% vs 10% with placebo and methotrexate). Other frequent events included elevated aspartate aminotransferase, elevated alanine aminotransferase, upper respiratory tract infection, dyspepsia and headache. There were two deaths in the trial - both patients were receiving golimumab. One death was from suicide, the other from cardiorespiratory arrest after surgery for a gluteal abscess. Two of the four malignancies that occurred in the trial were in patients receiving golimumab (breast cancer, Hodgkin's lymphoma). A patient receiving the higher golimumab dose was diagnosed with spinal tuberculosis (requiring surgery) eight weeks into the trial. ³

Golimumab has also been assessed in patients with active psoriatic arthritis (three or more swollen or tender joints) in the GO-REVEAL trial. This study enrolled patients who had not previously received tumour necrosis factor inhibitors. Patients were allowed to continue methotrexate, non-steroidal anti-inflammatory drugs (NSAIDs) and corticosteroids but were randomised to add injections of placebo (113 patients), golimumab 50 mg (146 patients) or golimumab 100 mg (146 patients) every four weeks. After 14 weeks, significantly more patients responded to golimumab than placebo (ACR20: 51% with 50 mg and 45% with 100 mg vs 9% with placebo). Patients receiving golimumab also had improvements in physical functioning and psoriasis symptoms (skin and nails). These benefits were irrespective of methotrexate use.

In the GO-REVEAL trial, upper respiratory tract infections and nasopharyngitis were the most commonly reported adverse events with golimumab and occurred more frequently than with placebo (10% and 10% with golimumab vs 6% and 4% with placebo). Elevated aspartate aminotransferase and alanine aminotransferase also occurred more frequently than with placebo. Alanine aminotransferase was increased in 24% of patients with golimumab 50 mg, 35% with golimumab 100 mg and 18% with placebo. Three malignancies were reported in the trial. These were in patients receiving the higher golimumab dose and included two cases of basal cell carcinoma and one case of prostate cancer. Other cancers were reported after the study period in patients who had received golimumab. These included small cell lung cancer (two cases), colon cancer, and basal cell carcinoma (two cases). A case of liver histoplasmosis was also reported in a patient who received golimumab. ⁴

Golimumab has also shown benefit in people with ankylosing spondylitis (GO-RAISE trial). (Concurrent treatment with methotrexate, sulfasalazine, hydroxychloroquine, corticosteroids and NSAIDs was allowed during the trial.) Of the 356 adults enrolled in the study, significantly more people randomised to monthly golimumab had a 20% improvement in their symptoms compared to those in the placebo group (59.4% with 50 mg and 60% with 100 mg vs 21.8%) after 14 weeks. Patients in the golimumab group also reported significant improvements in back pain, morning stiffness and pain at night, but not in range of motion. There were more infections with golimumab than placebo. Similarly, fatigue, headache, diarrhoea, injection-site erythema and elevated aspartate aminotransferase and alanine aminotransferase concentrations were more common with the study drug than with placebo. One patient on the lower dose of golimumab had a myocardial infarction despite normal cardiac assessment at baseline. ⁵

As golimumab affects the immune system there is a risk of serious infection, particularly in the elderly. Patients with active tuberculosis or other severe or opportunistic infections should not be given golimumab. If a patient tests positive for latent tuberculosis, they should be referred to a specialist for appropriate treatment before starting golimumab. It is important to monitor patients for infections while they are receiving golimumab. As the drug takes up to five months to clear from the body, patients should also be monitored after treatment has stopped. Patients should not be given live vaccines.

Golimumab has been associated with elevated liver enzymes so hepatic function should also be monitored during treatment.

Cancers, such as lymphoma, have occurred in patients given golimumab so caution is urged when prescribing this drug for patients who have a history of malignancy or develop a malignancy. Care should also be taken in patients with demyelinating disorders as golimumab can exacerbate these conditions.

Golimumab is contraindicated in moderate to severe heart failure. It should not be given with anakinra or abatacept. Some patients in the trials developed antinuclear antibodies following golimumab treatment, although none of them developed lupus-like symptoms.

A 50 mg dose of golimumab is recommended. It should be given subcutaneously once a month and patients may be able to do this themselves after training.

Golimumab was effective in rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis, and there seemed to be no advantage of the 100 mg dose over the 50 mg dose. Due to the lack of comparative trials, it is not known how it will compare to other tumour necrosis factor inhibitors currently used, although the fact that it can be self-administered once a month may be preferred by some patients.

manufacturer declined to supply data

The Transparency Score ( ) is explained in New drugs: transparency', Vol 37 No 1, Aust Prescr 2014;37:27.

Notes on references

At the time the comment was prepared, information about this drug was available on the web site of the Food and Drug Administration in the USA (www.fda.gov).

At the time the comment was prepared, a scientific discussion about this drug was available on the website of the European Medicines Agency (www.emea.europa.eu).