Golimumab interacts in the following cases:
Patients treated with golimumab may receive concurrent vaccinations, except for live vaccines. In patients receiving anti-TNF therapy, limited data are available on the response to vaccination with live vaccines or on the secondary transmission of infection by live vaccines. Use of live vaccines could result in clinical infections, including disseminated infections.
Other uses of therapeutic infectious agents such as live attenuated bacteria (e.g. BCG bladder instillation for the treatment of cancer) could result in clinical infections, including disseminated infections. It is recommended that therapeutic infectious agents not be given concurrently with golimumab.
Golimumab has not been studied in this patient population. No dose recommendations can be made. Golimumab should be used with caution in subjects with impaired hepatic function.
Golimumab has not been studied in this patient population. No dose recommendations can be made.
Golimumab should be used with caution in patients with mild heart failure (NYHA class I/II). Patients should be closely monitored and golimumab must be discontinued in patients who develop new or worsening symptoms of heart failure.
Serious infections and neutropenia were seen in clinical studies with concurrent use of anakinra and another TNF-blocking agent, etanercept, with no added clinical benefit. Because of the nature of the adverse events seen with this combination therapy, similar toxicities may also result from the combination of anakinra and other TNF-blocking agents. The combination of golimumab and anakinra is not recommended.
In clinical studies concurrent administration of TNF-antagonists and abatacept has been associated with an increased risk of infections including serious infections compared to TNF-antagonists alone, without increased clinical benefit. The combination of golimumab and abatacept is not recommended.
The potential role of TNF-blocking therapy in the development of malignancies is not known. Based on the current knowledge, a possible risk for the development of lymphomas, leukaemia or other malignancies in patients treated with a TNF-antagonist cannot be excluded. Caution should be exercised when considering TNF-blocking therapy for patients with a history of malignancy or when considering continuing treatment in patients who develop malignancy.
In an exploratory clinical trial evaluating the use of golimumab in patients with severe persistent asthma, more malignancies were reported in patients treated with golimumab compared with control patients. The significance of this finding is unknown.
In an exploratory clinical trial evaluating the use of another anti-TNF agent, infliximab, in patients with moderate to severe chronic obstructive pulmonary disease (COPD), more malignancies, mostly in the lung or head and neck, were reported in infliximab-treated patients compared with control patients. All patients had a history of heavy smoking. Therefore, caution should be exercised when using any TNF-antagonist in COPD patients, as well as in patients with an increased risk of malignancy due to heavy smoking.
The possibility exists for TNF-blocking agents, including golimumab, to affect host defences against infections and malignancies since TNF mediates inflammation and modulates cellular immune responses.
There is limited safety experience of golimumab treatment in patients who have undergone surgical procedures, including arthroplasty. The long half-life should be taken into consideration if a surgical procedure is planned. A patient who requires surgery while on golimumab should be closely monitored for infections, and appropriate actions should be taken.
In patients with pre-existing or recent onset of demyelinating disorders, the benefits and risks of anti-TNF treatment should be carefully considered before initiation of golimumab therapy. Discontinuation of golimumab should be considered if these disorders develop.
Patients should be tested for HBV infection before initiating treatment with golimumab. For patients who test positive for HBV infection, consultation with a physician with expertise in the treatment of hepatitis B is recommended.
Carriers of HBV who require treatment with golimumab should be closely monitored for signs and symptoms of active HBV infection throughout therapy and for several months following termination of therapy. Adequate data of treating patients who are carriers of HBV with anti-viral therapy in conjunction with TNF-antagonist therapy to prevent HBV reactivation are not available. In patients who develop HBV reactivation, golimumab should be stopped and effective anti-viral therapy with appropriate supportive treatment should be initiated.
There is a moderate amount (approximately 400) of prospectively collected pregnancies exposed to golimumab resulting in live birth with known outcomes, including 220 pregnancies exposed during the first trimester. In a population-based study from Northern Europe including 131 pregnancies (and 134 infants), there were 6/134 (4.5%) events of major congenital anomalies following in utero exposure to golimumab vs 599/10,823 (5.5%) events for non-biologic systemic therapy compared to 4.6% in the general population of the study. Confounder-adjusted odds ratios were OR 0.79 (95% CI 0.35-1.81) for golimumab vs. non-biologic systemic therapy and OR 0.95 (95% CI 0.42-2.16) for golimumab vs. the general population, respectively.
Due to its inhibition of TNF, golimumab administered during pregnancy could affect normal immune responses in the newborn. Studies in animals do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/foetal development, parturition or postnatal development. The available clinical experience is limited. Golimumab should only be used during pregnancy if clearly needed.
Golimumab crosses the placenta. Following treatment with a TNF-blocking monoclonal antibody during pregnancy, the antibody has been detected for up to 6 months in the serum of the infant born by the treated woman. Consequently, these infants may be at increased risk of infection. Administration of live vaccines to infants exposed to golimumab in utero is not recommended for 6 months following the mother's last golimumab injection during pregnancy.
It is not known whether golimumab is excreted in human milk or absorbed systemically after ingestion. Golimumab was shown to pass over to breast milk in monkeys, and because human immunoglobulins are excreted in milk, women must not breast feed during and for at least 6 months after golimumab treatment.
Women of childbearing potential must use adequate contraception to prevent pregnancy and continue its use for at least 6 months after the last golimumab treatment.
No animal fertility studies have been conducted with golimumab. A fertility study in mice, using an analogous antibody that selectively inhibits the functional activity of mouse TNF-α, showed no relevant effects on fertility.
Golimumab has minor influence on the ability to drive and use machines. Dizziness may however occur following administration of golimumab.
In the controlled period of the pivotal trials in RA, PsA, AS, nr-Axial SpA, and UC, upper respiratory tract infection was the most common adverse reaction (AR) reported in 12.6% of golimumab-treated patients compared with 11.0% of control patients. The most serious ARs that have been reported for golimumab include serious infections (including sepsis, pneumonia, TB, invasive fungal and opportunistic infections), demyelinating disorders, HBV reactivation, CHF, autoimmune processes (lupus-like syndrome), haematologic reactions, serious systemic hypersensitivity (including anaphylactic reaction), vasculitis, lymphoma and leukaemia.
ARs observed in clinical studies and reported from world-wide post-marketing use of golimumab are listed in the table below. Within the designated system organ classes, the ARs are listed under headings of frequency and using the following convention: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000); not known (cannot be estimated from the available data). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.
Tabulated list of ARs:
| Infections and infestations | |
| Very common: | Upper respiratory tract infection (nasopharyngitis, pharyngitis, laryngitis and rhinitis) |
| Common: | Bacterial infections (such as cellulitis), lower respiratory tract infection (such as pneumonia), viral infections (such as influenza and herpes), bronchitis, sinusitis, superficial fungal infections, abscess |
| Uncommon: | Sepsis including septic shock, pyelonephritis |
| Neoplasms, benign, malignant and unspecified | |
| Uncommon: | Neoplasms (such as skin cancer, squamous cell carcinoma and melanocytic naevus) |
| Rare: | Lymphoma, leukaemia, melanoma, Merkel cell carcinoma |
| Not known: | Hepatosplenic T-cell lymphoma*, Kaposi's sarcoma |
| Blood and lymphatic system disorders | |
| Common: | Leukopenia (including neutropenia), anaemia |
| Uncommon: | Thrombocytopenia, pancytopenia |
| Rare: | Aplastic anaemia, agranulocytosis |
| Immune system disorders | |
| Common: | Allergic reactions (bronchospasm, hypersensitivity, urticaria), autoantibody positive |
| Rare: | Serious systemic hypersensitivity reactions (including anaphylactic reaction), vasculitis (systemic), sarcoidosis |
| Endocrine disorders | |
| Uncommon: | Thyroid disorder (such as hypothyroidism, hyperthyroidism and goitre) |
| Metabolism and nutrition disorders | |
| Uncommon: | Blood glucose increased, lipids increased |
| Psychiatric disorders | |
| Common: | Depression, insomnia |
| Nervous system disorders | |
| Common: | Dizziness, headache, paraesthesia |
| Uncommon: | Balance disorders |
| Rare: | Demyelinating disorders (central and peripheral), dysgeusia |
| Eye disorders | |
| Uncommon: | Visual disorders (such as blurred vision and decreased visual acuity), conjunctivitis, eye allergy (such as pruritus and irritation) |
| Cardiac disorders | |
| Uncommon: | Arrhythmia, ischaemic coronary artery disorders |
| Rare: | Congestive heart failure (new onset or worsening) |
| Vascular disorders | |
| Common: | Hypertension |
| Uncommon: | Thrombosis (such as deep venous and aortic), flushing |
| Rare: | Raynaud's phenomenon |
| Respiratory, thoracic and mediastinal disorders | |
| Common: | Asthma and related symptoms (such as wheezing and bronchial hyperactivity) |
| Uncommon: | Interstitial lung disease |
| Gastrointestinal disorders | |
| Common: | Dyspepsia, gastrointestinal and abdominal pain, nausea, gastrointestinal inflammatory disorders (such as gastritis and colitis), stomatitis |
| Uncommon: | Constipation, gastro-oesophageal reflux disease |
| Hepatobiliary disorders | |
| Common: | Alanine aminotransferase increased, aspartate aminotransferase increased |
| Uncommon: | Cholelithiasis, hepatic disorders |
| Skin and subcutaneous tissue disorders | |
| Common: | Pruritus, rash, alopecia, dermatitis |
| Uncommon: | Bullous skin reactions, psoriasis (new onset or worsening of pre-existing psoriasis, palmar/plantar and pustular), urticaria |
| Rare: | Lichenoid reactions, skin exfoliation, vasculitis (cutaneous) |
| Not known: | Worsening of symptoms of dermatomyositis |
| Musculoskeletal and connective tissue disorders | |
| Rare: | Lupus-like syndrome |
| Renal and urinary disorders | |
| Rare: | Bladder disorders, renal disorders |
| Reproductive system and breast disorders | |
| Uncommon: | Breast disorders, menstrual disorders |
| General disorders and administration site conditions | |
| Common: | Pyrexia, asthenia, injection site reaction (such as injection site erythema, urticaria, induration, pain, bruising, pruritus, irritation and paraesthesia), chest discomfort |
| Rare: | Impaired healing |
| Injury, poisoning and procedural complications | |
| Common: | Bone fractures |
* Observed with other TNF-blocking agents
Throughout this section, median duration of follow-up (approximately 4 years) is generally presented for all golimumab use. Where golimumab use is described by dose, the median duration of follow-up varies (approximately 2 years for 50 mg dose, approximately 3 years for 100 mg dose) as patients may have switched between doses.
In the controlled period of pivotal trials, upper respiratory tract infection was the most common adverse reaction reported in 12.6% of golimumab-treated patients (incidence per 100 subject-years: 60.8; 95% CI: 55.0, 67.1) compared with 11.0% of control patients (incidence per 100 subject-years: 54.5; 95% CI: 46.1, 64.0). In controlled and uncontrolled portions of the studies with a median follow-up of approximately 4 years, the incidence per 100 subject-years of upper respiratory tract infections was 34.9 events; 95% CI: 33.8, 36.0 for golimumab treated patients.
In the controlled period of pivotal trials, infections were observed in 23.0% of golimumab-treated patients (incidence per 100 subject-years: 132.0; 95% CI: 123.3, 141.1) compared with 20.2% of control patients (incidence per 100 subject-years: 122.3; 95% CI: 109.5, 136.2). In controlled and uncontrolled portions of the trials with a median follow-up of approximately 4 years, the incidence per 100 subject-years of infections was 81.1 events; 95% CI: 79.5, 82.8 for golimumab treated patients.
In the controlled period of RA, PsA, AS, and nr-Axial SpA trials, serious infections were observed in 1.2% of golimumab-treated patients and 1.2% of control-treated patients. The incidence of serious infections per 100 subject-years of follow-up in the controlled period of RA, PsA, AS, and nr-Axial SpA trials was 7.3; 95% CI: 4.6, 11.1 for the golimumab 100 mg group, 2.9; 95% CI: 1.2, 6.0 for the golimumab 50 mg group and 3.6; 95% CI: 1.5, 7.0 for the placebo group. In the controlled period of UC trials of golimumab induction, serious infections were observed in 0.8% of golimumab-treated patients compared with 1.5% of control-treated patients. Serious infections observed in golimumab-treated patients included tuberculosis, bacterial infections including sepsis and pneumonia, invasive fungal infections and other opportunistic infections. Some of these infections have been fatal. In the controlled and uncontrolled portions of the pivotal trials with a median follow-up of up to 3 years, there was a greater incidence of serious infections, including opportunistic infections and TB in patients receiving golimumab 100 mg compared with patients receiving golimumab 50 mg. The incidence per 100 subject-years of all serious infections was 4.1; 95% CI: 3.6, 4.5, in patients receiving golimumab 100 mg and 2.5; 95% CI: 2.0, 3.1, in patients receiving golimumab 50 mg.
The incidence of lymphoma in golimumab-treated patients during the pivotal trials was higher than expected in the general population. In the controlled and uncontrolled portions of these trials with a median follow-up of up to 3 years, a greater incidence of lymphoma was observed in patients receiving golimumab 100 mg compared with patients receiving golimumab 50 mg. Lymphoma was diagnosed in 11 subjects (1 in the golimumab 50 mg treatment groups and 10 in the golimumab 100 mg treatment groups) with an incidence (95% CI) per 100 subject-years of follow-up of 0.03 (0.00, 0.15) and 0.13 (0.06, 0.24) events for golimumab 50 mg and 100 mg respectively and 0.00 (0.00, 0.57) events for the placebo. The majority of lymphomas occurred in study GO-AFTER, which enrolled patients previously exposed to anti-TNF agents who had longer disease duration and more refractory disease.
In the controlled periods of pivotal trials and through approximately 4 years of follow-up, the incidence of non-lymphoma malignancies (excluding non-melanoma skin cancer) was similar between the golimumab and the control groups. Through approximately 4 years of follow-up, the incidence of non-lymphoma malignancies (excluding non-melanoma skin cancer) was similar to the general population.
In the controlled and uncontrolled periods of pivotal trials with a median follow-up of up to 3 years, non-melanoma skin cancer was diagnosed in 5 placebo-treated, 10 golimumab 50 mg-treated and 31 golimumab 100 mg-treated subjects with an incidence (95% CI) per 100 subject-years of follow-up of 0.36 (0.26, 0.49) for combined golimumab and 0.87 (0.28, 2.04) for placebo.
In the controlled and uncontrolled period of pivotal trials with a median follow-up of up to 3 years, malignancies besides melanoma, non-melanoma skin cancer and lymphoma were diagnosed in 5 placebo-treated, 21 golimumab 50 mg-treated and 34 golimumab 100 mg-treated subjects with an incidence (95% CI) per 100 subject-years of follow-up of 0.48 (0.36, 0.62) for combined golimumab and 0.87 (0.28, 2.04) for placebo.
In an exploratory clinical study, patients with severe persistent asthma received a golimumab loading dose (150% of the assigned treatment dose) subcutaneously at week 0 followed by golimumab 200 mg, golimumab 100 mg or golimumab 50 mg every 4 weeks subcutaneously through week 52. Eight malignancies in the combined golimumab treatment group (n=230) and none in the placebo treatment group (n=79) were reported. Lymphoma was reported in 1 patient, non-melanoma skin cancer in 2 patients, and other malignancies in 5 patients. There was no specific clustering of any type of malignancy.
During the placebo-controlled portion of the study, the incidence (95% CI) of all malignancies per 100 subject-years of follow-up was 3.19 (1.38, 6.28) in the golimumab group. In this study, the incidence (95% CI) per 100 subject-years of follow-up in golimumab-treated subjects was 0.40 (0.01, 2.20) for lymphoma, 0.79 (0.10, 2.86) for non-melanoma skin cancers, and 1.99 (0.64, 4.63) for other malignancies. For placebo subjects, the incidence (95% CI) per 100 subject-years of follow-up of these malignancies was 0.00 (0.00, 2.94). The significance of this finding is unknown.
In the controlled and uncontrolled periods of the pivotal trials with a median follow-up of up to 3 years, a greater incidence of demyelination was observed in patients receiving golimumab 100 mg compared with patients receiving golimumab 50 mg.
In the controlled period of RA and PsA pivotal trials, mild ALT elevations (>1 and <3 x upper limit of normal (ULN)) occurred in similar proportions of golimumab and control patients in the RA and PsA studies (22.1% to 27.4% of patients); in the AS and nr-Axial SpA studies, more golimumab-treated patients (26.9%) than control patients (10.6%) had mild ALT elevations. In the controlled and uncontrolled periods of the RA and PsA pivotal trials, with a median follow-up of approximately 5 years, the incidence of mild ALT elevations was similar in golimumab-treated and control patients in RA and PsA studies. In the controlled period of the UC pivotal trials of golimumab induction, mild ALT elevations (>1 and <3 x ULN) occurred in similar proportions of golimumab-treated and control patients (8.0% to 6.9%, respectively). In controlled and uncontrolled periods of the UC pivotal trials with a median follow-up of approximately 2 years, the proportion of patients with mild ALT elevations was 24.7% in patients receiving golimumab during the maintenance portion of the UC study.
In the controlled period of RA and AS pivotal trials, ALT elevations ≥5 x ULN were uncommon and seen in more golimumab-treated patients (0.4% to 0.9%) than control patients (0.0%). This trend was not observed in the PsA population. In the controlled and uncontrolled periods of RA, PsA and AS pivotal trials, with a median follow-up of 5 years, the incidence of ALT elevations ≥5 x ULN was similar in both golimumab-treated and control patients. In general these elevations were asymptomatic and the abnormalities decreased or resolved with either continuation or discontinuation of golimumab or modification of concomitant medicinal products. No cases were reported in the controlled and uncontrolled periods of the nr-Axial SpA study (up to 1 year). In the controlled periods of the pivotal UC trials, of golimumab induction, ALT elevations ≥5 x ULN occurred in similar proportions of golimumab-treated patients compared to placebo-treated patients (0.3% to 1.0%, respectively). In the controlled and uncontrolled periods of the pivotal UC trials with a median follow-up of approximately 2 years, the proportion of patients with ALT elevations ≥5 x ULN was 0.8% in patients receiving golimumab during the maintenance portion of the UC study.
Within the RA, PsA, AS, and nr-Axial SpA pivotal trials, one patient in an RA trial with pre-existing liver abnormalities and confounding medicinal products treated with golimumab developed non-infectious fatal hepatitis with jaundice. The role of golimumab as a contributing or aggravation factor cannot be excluded.
In the controlled periods of pivotal trials, 5.4% of golimumab-treated patients had injection site reactions compared with 2.0% in control patients. The presence of antibodies to golimumab may increase the risk of injection site reactions. The majority of the injection site reactions were mild and moderate and the most frequent manifestation was injection site erythema. Injection site reactions generally did not necessitate discontinuation of the medicinal product.
In controlled Phase IIb and/or III trials in RA, PsA, AS, nr-Axial SpA, severe persistent asthma, and Phase II/III trials in UC, no patients treated with golimumab developed anaphylactic reactions.
In the controlled and uncontrolled periods of pivotal trials through 1 year of follow-up, 3.5% of golimumab-treated patients and 2.3% of control patients were newly ANA-positive (at titres of 1:160 or greater). The frequency of anti-dsDNA antibodies at 1 year of follow-up in patients anti-dsDNA negative at baseline was 1.1%.
The safety of golimumab has been studied in a Phase III study of 173 pJIA patients from 2 to 17 years of age. The average follow-up was approximately two years. In this study, the type and frequency of adverse events reported were generally similar to those seen in adult RA studies.
The safety of golimumab has been studied in a Phase III study of 69 patients from 4 to 17 years of age with moderately to severely active ulcerative colitis. In this study, adverse reactions observed were consistent with the established safety profile of golimumab in adult patients with UC.
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