Simponi® 50 mg solution for injection in pre-filled pen.

Simponi® 50 mg solution for injection in pre-filled syringe.

Simponi 50 mg solution for injection in pre-filled pen

One 0.5 mL pre-filled pen contains 50 mg of golimumab*.

Simponi 50 mg solution for injection in pre-filled syringe

One 0.5 mL pre-filled syringe contains 50 mg of golimumab*.

* Human IgG1κ monoclonal antibody produced by a murine hybridoma cell line with recombinant DNA technology.

Excipient with known effect

Each pre-filled pen contains 20.5 mg sorbitol per 50 mg dose.

Each pre-filled syringe contains 20.5 mg sorbitol per 50 mg dose.

For the full list of excipients, see section 6.1.

Solution for injection in pre-filled pen (injection), SmartJect

Solution for injection in pre-filled syringe (injection)

The solution is clear to slightly opalescent, colourless to light yellow.

Rheumatoid arthritis (RA)

Simponi, in combination with methotrexate (MTX), is indicated for:

• the treatment of moderate to severe, active rheumatoid arthritis in adults when the response to disease-modifying anti-rheumatic drug (DMARD) therapy including MTX has been inadequate.

• the treatment of severe, active and progressive rheumatoid arthritis in adults not previously treated with MTX.

Simponi, in combination with MTX, has been shown to reduce the rate of progression of joint damage as measured by X-ray and to improve physical function.

Juvenile idiopathic arthritis

Polyarticular juvenile idiopathic arthritis (pJIA)

Simponi in combination with MTX is indicated for the treatment of polyarticular juvenile idiopathic arthritis in children 2 years of age and older, who have responded inadequately to previous therapy with MTX.

Psoriatic arthritis (PsA)

Simponi, alone or in combination with MTX, is indicated for the treatment of active and progressive psoriatic arthritis in adult patients when the response to previous DMARD therapy has been inadequate. Simponi has been shown to reduce the rate of progression of peripheral joint damage as measured by X-ray in patients with polyarticular symmetrical subtypes of the disease (see section 5.1) and to improve physical function.

Axial spondyloarthritis

Ankylosing spondylitis (AS)

Simponi is indicated for the treatment of severe, active ankylosing spondylitis in adults who have responded inadequately to conventional therapy.

Non-radiographic axial spondyloarthritis (nr-Axial SpA)

Simponi is indicated for the treatment of adults with severe, active non-radiographic axial spondyloarthritis with objective signs of inflammation as indicated by elevated C-reactive protein (CRP) and/or magnetic resonance imaging (MRI) evidence, who have had an inadequate response to, or are intolerant to nonsteroidal anti-inflammatory drugs (NSAIDs).

Ulcerative colitis (UC)

Simponi is indicated for treatment of moderately to severely active ulcerative colitis in adult patients who have had an inadequate response to conventional therapy including corticosteroids and 6-mercaptopurine (6-MP) or azathioprine (AZA), or who are intolerant to or have medical contraindications for such therapies.

Treatment is to be initiated and supervised by qualified physicians experienced in the diagnosis and treatment of rheumatoid arthritis, polyarticular juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, non-radiographic axial spondyloarthritis, or ulcerative colitis. Patients treated with Simponi should be given the Patient Reminder Card.

Posology

Rheumatoid arthritis

Simponi 50 mg given once a month, on the same date each month.

Simponi should be given concomitantly with MTX.

Psoriatic arthritis, ankylosing spondylitis, or non-radiographic axial spondyloarthritis

Simponi 50 mg given once a month, on the same date each month.

For all of the above indications, available data suggest that clinical response is usually achieved within 12 to 14 weeks of treatment (after 3-4 doses). Continued therapy should be reconsidered in patients who show no evidence of therapeutic benefit within this time period.

Patients with body weight greater than 100 kg

For all of the above indications, in patients with RA, PsA, AS, or nr-Axial SpA with a body weight of more than 100 kg who do not achieve an adequate clinical response after 3 or 4 doses, increasing the dose of golimumab to 100 mg once a month may be considered, taking into account the increased risk of certain serious adverse reactions with the 100 mg dose compared with the 50 mg dose (see section 4.8). Continued therapy should be reconsidered in patients who show no evidence of therapeutic benefit after receiving 3 to 4 additional doses of 100 mg.

Ulcerative colitis

Patients with body weight less than 80 kg

Simponi given as an initial dose of 200 mg, followed by 100 mg at week 2. Patients who have an adequate response should receive 50 mg at week 6 and every 4 weeks thereafter. Patients who have an inadequate response may benefit from continuing with 100 mg at week 6 and every 4 weeks thereafter (see section 5.1).

Patients with body weight greater than or equal to 80 kg

Simponi given as an initial dose of 200 mg, followed by 100 mg at week 2, then 100 mg every 4 weeks, thereafter (see section 5.1).

During maintenance treatment, corticosteroids may be tapered in accordance with clinical practice guidelines.

Available data suggest that clinical response is usually achieved within 12-14 weeks of treatment (after 4 doses). Continued therapy should be reconsidered in patients who show no evidence of therapeutic benefit within this time period.

Missed dose

If a patient forgets to inject Simponi on the planned date, the forgotten dose should be injected as soon as the patient remembers. Patients should be instructed not to inject a double dose to make up for the forgotten dose.

The next dose should be administered based on the following guidance:

• if the dose is less than 2 weeks late, the patient should inject the forgotten dose and stay on the original schedule.

• if the dose is more than 2 weeks late, the patient should inject the forgotten dose and a new schedule should be established from the date of this injection.

Special populations

Elderly (≥ 65 years)

No dose adjustment is required in the elderly.

Renal and hepatic impairment

Simponi has not been studied in these patient populations. No dose recommendations can be made.

Paediatric population

The safety and efficacy of Simponi in patients aged less than 18 for indications other than pJIA have not been established.

Polyarticular juvenile idiopathic arthritis

Simponi 50 mg administered once a month, on the same date each month, for children with a body weight of at least 40 kg. A 45 mg/0.45 mL pre-filled pen is available* for administration to children with polyarticular juvenile idiopathic arthritis weighing less than 40 kg.

Available data suggest that clinical response is usually achieved within 12 to 14 weeks of treatment (after 3-4 doses). Continued therapy should be reconsidered in children who show no evidence of therapeutic benefit within this time period.

Method of administration

Simponi is for subcutaneous use. After proper training in subcutaneous injection technique, patients may self-inject if their physician determines that this is appropriate, with medical follow-up as necessary. Patients should be instructed to inject the full amount of Simponi according to the comprehensive instructions for use provided in the package leaflet. If multiple injections are required, the injections should be administered at different sites on the body.

For administration instructions, see section 6.6.

*May not be available in all EU markets.

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

Active tuberculosis (TB) or other severe infections such as sepsis, and opportunistic infections (see section 4.4).

Moderate or severe heart failure (NYHA class III/IV) (see section 4.4).

Traceability

In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded.

Infections

Patients must be monitored closely for infections including tuberculosis before, during and after treatment with golimumab. Because the elimination of golimumab may take up to 5 months, monitoring should be continued throughout this period. Further treatment with golimumab must not be given if a patient develops a serious infection or sepsis (see section 4.3).

Golimumab should not be given to patients with a clinically important, active infection. Caution should be exercised when considering the use of golimumab in patients with a chronic infection or a history of recurrent infection. Patients should be advised of, and avoid exposure to, potential risk factors for infection as appropriate.

Patients taking TNF-blockers are more susceptible to serious infections.

Bacterial (including sepsis and pneumonia), mycobacterial (including TB), invasive fungal and opportunistic infections, including fatalities, have been reported in patients receiving golimumab. Some of these serious infections have occurred in patients on concomitant immunosuppressive therapy that, in addition to their underlying disease, could predispose them to infections. Patients who develop a new infection while undergoing treatment with golimumab should be monitored closely and undergo a complete diagnostic evaluation. Administration of golimumab should be discontinued if a patient develops a new serious infection or sepsis, and appropriate antimicrobial or antifungal therapy should be initiated until the infection is controlled.

For patients who have resided in or travelled to regions where invasive fungal infections such as histoplasmosis, coccidioidomycosis, or blastomycosis are endemic, the benefits and risks of golimumab treatment should be carefully considered before initiation of golimumab therapy. In at-risk patients treated with golimumab, an invasive fungal infection should be suspected if they develop a serious systemic illness. Diagnosis and administration of empiric antifungal therapy in these patients should be made in consultation with a physician with expertise in the care of patients with invasive fungal infections, if feasible.

Tuberculosis

There have been reports of tuberculosis in patients receiving golimumab. It should be noted that in the majority of these reports, tuberculosis was extrapulmonary presenting as either local or disseminated disease.

Before starting treatment with golimumab, all patients must be evaluated for both active and inactive ('latent') tuberculosis. This evaluation should include a detailed medical history with personal history of tuberculosis or possible previous contact with tuberculosis and previous and/or current immunosuppressive therapy. Appropriate screening tests, i.e. tuberculin skin or blood test and chest X-ray, should be performed in all patients (local recommendations may apply). It is recommended that the conduct of these tests should be recorded in the Patient Reminder Card. Prescribers are reminded of the risk of false negative tuberculin skin test results, especially in patients who are severely ill or immunocompromised.

If active tuberculosis is diagnosed, golimumab therapy must not be initiated (see section 4.3).

If latent tuberculosis is suspected, a physician with expertise in the treatment of tuberculosis should be consulted. In all situations described below, the benefit/risk balance of golimumab therapy should be very carefully considered.

If inactive ('latent') tuberculosis is diagnosed, treatment for latent tuberculosis must be started with anti-tuberculosis therapy before the initiation of golimumab, and in accordance with local recommendations.

In patients who have several or significant risk factors for tuberculosis and have a negative test for latent tuberculosis, anti-tuberculosis therapy should be considered before the initiation of golimumab. Use of anti-tuberculosis therapy should also be considered before the initiation of golimumab in patients with a past history of latent or active tuberculosis in whom an adequate course of treatment cannot be confirmed.

Cases of active tuberculosis have occurred in patients treated with golimumab during and after treatment for latent tuberculosis. Patients receiving golimumab should be monitored closely for signs and symptoms of active tuberculosis, including patients who tested negative for latent tuberculosis, patients who are on treatment for latent tuberculosis, or patients who were previously treated for tuberculosis infection.

All patients should be informed to seek medical advice if signs/symptoms suggestive of tuberculosis (e.g. persistent cough, wasting/weight loss, low-grade fever) appear during or after golimumab treatment.

Hepatitis B virus reactivation

Reactivation of hepatitis B has occurred in patients receiving a TNF-antagonist including golimumab, who are chronic carriers of this virus (i.e. surface antigen positive). Some cases have had fatal outcome.

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.

Malignancies and lymphoproliferative disorders

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.

Paediatric malignancy

Malignancies, some fatal, have been reported among children, adolescents and young adults (up to 22 years of age) treated with TNF-blocking agents (initiation of therapy ≤ 18 years of age) in the post marketing setting. Approximately half the cases were lymphomas. The other cases represented a variety of different malignancies and included rare malignancies usually associated with immunosuppression. A risk for the development of malignancies in children and adolescents treated with TNF-blockers cannot be excluded.

Lymphoma and leukaemia

In the controlled portions of clinical trials of all the TNF-blocking agents including golimumab, more cases of lymphoma have been observed among patients receiving anti-TNF treatment compared with control patients. During the Simponi Phase IIb and Phase III clinical trials in RA, PsA and AS, the incidence of lymphoma in golimumab-treated patients was higher than expected in the general population. Cases of leukaemia have been reported in patients treated with golimumab. There is an increased background risk for lymphoma and leukaemia in rheumatoid arthritis patients with long-standing, highly active, inflammatory disease, which complicates risk estimation.

Rare post-marketing cases of hepatosplenic T-cell lymphoma (HSTCL) have been reported in patients treated with other TNF-blocking agents (see section 4.8). This rare type of T-cell lymphoma has a very aggressive disease course and is usually fatal. The majority of cases have occurred in adolescent and young adult males with nearly all on concomitant treatment with azathioprine (AZA) or 6-mercaptopurine (6–MP) for inflammatory bowel disease. The potential risk with the combination of AZA or 6-MP and golimumab should be carefully considered. A risk for the development for hepatosplenic T-cell lymphoma in patients treated with TNF-blockers cannot be excluded.

Malignancies other than lymphoma

In the controlled portions of the Simponi Phase IIb and Phase III clinical trials in RA, PsA, AS, and UC, the incidence of non-lymphoma malignancies (excluding non-melanoma skin cancer) was similar between the golimumab and the control groups.

Colon dysplasia/carcinoma

It is not known if golimumab treatment influences the risk for developing dysplasia or colon cancer. All patients with ulcerative colitis who are at increased risk for dysplasia or colon carcinoma (for example, patients with long-standing ulcerative colitis or primary sclerosing cholangitis), or who had a prior history of dysplasia or colon carcinoma should be screened for dysplasia at regular intervals before therapy and throughout their disease course. This evaluation should include colonoscopy and biopsies per local recommendations. In patients with newly diagnosed dysplasia treated with golimumab, the risks and benefits to the individual patient must be carefully reviewed and consideration should be given to whether therapy should be continued.

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 (see section 4.8). 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.

Skin cancers

Melanoma and Merkel cell carcinoma have been reported in patients treated with TNF-blocking agents, including golimumab (see section 4.8). Periodic skin examination is recommended, particularly for patients with risk factors for skin cancer.

Congestive heart failure (CHF)

Cases of worsening congestive heart failure (CHF) and new onset CHF have been reported with TNF blockers, including golimumab. Some cases had a fatal outcome. In a clinical trial with another TNF-antagonist worsening congestive heart failure and increased mortality due to CHF have been observed. Golimumab has not been studied in patients with CHF. 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 (see section 4.3).

Neurological events

Use of TNF-blocking agents, including golimumab, has been associated with cases of new onset or exacerbation of clinical symptoms and/or radiographic evidence of central nervous system demyelinating disorders, including multiple sclerosis and peripheral demyelinating disorders. 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 (see section 4.8).

Surgery

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.

Immunosuppression

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.

Autoimmune processes

The relative deficiency of TNFα caused by anti-TNF therapy may result in the initiation of an autoimmune process. If a patient develops symptoms suggestive of a lupus-like syndrome following treatment with golimumab and is positive for antibodies against double-stranded DNA, treatment with golimumab should be discontinued (see section 4.8).

Haematologic reactions

There have been reports of pancytopenia, leukopenia, neutropenia, agranulocytosis, aplastic anaemia, and thrombocytopenia in patients receiving TNF-blockers, including golimumab. All patients should be advised to seek immediate medical attention if they develop signs and symptoms suggestive of blood dyscrasias (e.g. persistent fever, bruising, bleeding, pallor). Discontinuation of golimumab therapy should be considered in patients with confirmed significant haematologic abnormalities.

Concurrent administration of TNF-antagonists and anakinra

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.

Concurrent administration of TNF-antagonists and abatacept

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.

Concurrent administration with other biological therapeutics

There is insufficient information regarding the concomitant use of golimumab with other biological therapeutics used to treat the same conditions as golimumab. The concomitant use of golimumab with these biologics is not recommended because of the possibility of an increased risk of infection, and other potential pharmacological interactions.

Switching between biological DMARDs

Care should be taken and patients should continue to be monitored when switching from one biologic to another, since overlapping biological activity may further increase the risk for adverse events, including infection.

Vaccinations/therapeutic infectious agents

Patients treated with golimumab may receive concurrent vaccinations, except for live vaccines (see sections 4.5 and 4.6). 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.

Allergic reactions

In post-marketing experience, serious systemic hypersensitivity reactions (including anaphylactic reaction) have been reported following golimumab administration. Some of these reactions occurred after the first administration of golimumab. If an anaphylactic reaction or other serious allergic reactions occur, administration of golimumab should be discontinued immediately and appropriate therapy initiated.

Latex sensitivity

The needle cover on the pre-filled pen or the pre-filled syringe is manufactured from dry natural rubber containing latex, and may cause allergic reactions in individuals sensitive to latex.

Special populations

Elderly (≥ 65 years)

In the Phase III studies in RA, PsA, AS, and UC, no overall differences in adverse events (AEs), serious adverse events (SAEs), and serious infections in patients age 65 or older who received golimumab were observed compared with younger patients. However, caution should be exercised when treating the elderly and particular attention paid with respect to occurrence of infections. There were no patients age 45 and over in the nr-Axial SpA study.

Renal and hepatic impairment

Specific studies of golimumab have not been conducted in patients with renal or hepatic impairment. Golimumab should be used with caution in subjects with impaired hepatic function (see section 4.2).

Paediatrics

Vaccinations

If possible, it is recommended that prior to initiating golimumab therapy, paediatric patients be brought up to date with all immunisations in agreement with current immunisation guidelines (see Vaccinations/therapeutic infectious agents above).

Excipients

Simponi contains sorbitol (E420). In patients with rare hereditary problems of fructose intolerance, the additive effect of concomitantly administered products containing sorbitol (or fructose) and dietary intake of sorbitol (or fructose) should be taken into account (see section 2).

Potential for medication errors

Simponi is registered in 50 mg and 100 mg strengths for subcutaneous administration. It is important that the right strength is used to administer the correct dose as indicated in the posology (see section 4.2). Care should be taken to provide the right strength to ensure that patients are not underdosed or overdosed.

No interaction studies have been performed.

Concurrent use with other biological therapeutics

The combination of golimumab with other biological therapeutics used to treat the same conditions as golimumab, including anakinra and abatacept is not recommended (see section 4.4).

Live vaccines/therapeutic infectious agents

Live vaccines should not be given concurrently with golimumab (see sections 4.4 and 4.6).

Therapeutic infectious agents should not be given concurrently with golimumab (see section 4.4).

Methotrexate

Although concomitant use of MTX results in higher steady-state trough concentrations of golimumab in patients with RA, PsA or AS, the data do not suggest the need for dose adjustment of either golimumab or MTX (see section 5.2).

Women of childbearing potential

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.

Pregnancy

There are no adequate data on the use of golimumab in pregnant women. 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 (see section 5.3). The use of golimumab in pregnant women is not recommended; golimumab should be given to a pregnant woman only 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 (see sections 4.4 and 4.5).

Breast-feeding

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.

Fertility

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 TNFα, showed no relevant effects on fertility (see section 5.3).

Simponi has minor influence on the ability to drive and use machines. Dizziness may however occur following administration of Simponi (see section 4.8).

Summary of the safety profile

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 (see section 4.4).

Tabulated list of adverse reactions

ARs observed in clinical studies and reported from world-wide post-marketing use of golimumab are listed in Table 1. 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.

Table 1

Tabulated list of ARs