Симпони

Rheumatoid arthritis (RA)

Симпони, 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.

Симпони, 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.

For information regarding the polyarticular juvenile idiopathic arthritis indication, please see the Симпони 50 mg SmPC.

Psoriatic arthritis (PsA)

Симпони, 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. Симпони 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 and to improve physical function.

Axial spondyloarthritis

Ankylosing spondylitis (AS)

Симпони 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)

Симпони 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)

Симпони 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.

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

Posology

Rheumatoid arthritis

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

Симпони should be given concomitantly with MTX.

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

Симпони 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 bodyweight 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 drug reactions with the 100 mg dose compared with the 50 mg dose. 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

Симпони given as an initial dose of 200 mg, followed by 100 mg at week 2, then 50 mg every 4 weeks, thereafter.

Patients with body weight greater than or equal to 80 kg

Симпони given as an initial dose of 200 mg, followed by 100 mg at week 2, then 100 mg every 4 weeks, thereafter.

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 Симпони 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 his/her forgotten dose and stay on his/her original schedule.

- if the dose is more than 2 weeks late, the patient should inject his/her 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

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

Paediatric population

Симпони 100 mg is not recommended in children aged less than 18.

Method of administration

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

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

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

Infections

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

Симпони should not be given to patients with a clinically important, active infection. Caution should be exercised when considering the use of Симпони 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 Симпони. 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 Симпони should be monitored closely and undergo a complete diagnostic evaluation. Administration of Симпони 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 Симпони treatment should be carefully considered before initiation of Симпони therapy. In at-risk patients treated with Симпони, 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 Симпони. 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 Симпони, 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's alert 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, Симпони therapy must not be initiated.

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 Симпони 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 Симпони, 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 Симпони. Use of anti-tuberculosis therapy should also be considered before the initiation of Симпони 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 Симпони during and after treatment for latent tuberculosis. Patients receiving Симпони 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 Симпони treatment.

Hepatitis B virus reactivation

Reactivation of hepatitis B has occurred in patients receiving a TNF-antagonist including Симпони, 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 Симпони. 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 Симпони 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, Симпони 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 Симпони, more cases of lymphoma have been observed among patients receiving anti-TNF treatment compared with control patients. During the Симпони Phase IIb and Phase III clinical trials in RA, PsA and AS, the incidence of lymphoma in Симпони-treated patients was higher than expected in the general population. Cases of leukaemia have been reported in patients treated with Симпони. 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. 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 Симпони 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 Симпони 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 Симпони 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 Симпони, 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 Симпони in patients with severe persistent asthma, more malignancies were reported in patients treated with Симпони 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.

Skin cancers

Melanoma and Merkel cell carcinoma have been reported in patients treated with TNF-blocking agents, including Симпони. 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 Симпони. 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. Симпони has not been studied in patients with CHF. Симпони should be used with caution in patients with mild heart failure (NYHA class I/II). Patients should be closely monitored and Симпони must be discontinued in patients who develop new or worsening symptoms of heart failure.

Neurological events

Use of TNF-blocking agents, including Симпони, 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 Симпони therapy. Discontinuation of Симпони should be considered if these disorders develop.

Surgery

There is limited safety experience of Симпони 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 Симпони should be closely monitored for infections, and appropriate actions should be taken.

Immunosuppression

The possibility exists for TNF-blocking agents, including Симпони, to affect host defences against infections and malignancies since TNF mediates inflammation and modulates cellular immune responses.

Autoimmune processes

The relative deficiency of TNF_α 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 Симпони and is positive for antibodies against double-stranded DNA, treatment with Симпони should be discontinued.

Haematologic reactions

There have been reports of pancytopenia, leukopenia, neutropenia, agranulocytosis, aplastic anaemia, and thrombocytopenia in patients receiving TNF-blockers, including Симпони. 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 Симпони 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 Симпони 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 Симпони and abatacept is not recommended.

Concurrent administration with other biological therapeutics

There is insufficient information regarding the concomitant use of Симпони with other biological therapeutics used to treat the same conditions as Симпони. The concomitant use of Симпони 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 Симпони 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 Симпони.

Allergic reactions

In post-marketing experience, serious systemic hypersensitivity reactions (including anaphylactic reaction) have been reported following Симпони administration. Some of these reactions occurred after the first administration of Симпони. If an anaphylactic reaction or other serious allergic reactions occur, administration of Симпони 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 Симпони 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 Симпони have not been conducted in patients with renal or hepatic impairment. Симпони should be used with caution in subjects with impaired hepatic function.

Excipients

Симпони contains sorbitol (E420). Patients with rare hereditary problems of fructose intolerance should not take Симпони.

Potential for medication errors

Симпони 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. Care should be taken to provide the right strength to ensure that patients are not underdosed or overdosed.

Симпони may have a minor influence on the ability to drive and use machines. Dizziness may occur following administration of Симпони.

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 drug reaction (ADR) reported in 12.6% of golimumab-treated patients compared with 11.0% of control patients. The most serious ADRs 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.

Tabulated list of adverse reactions

ADRs 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 adverse drug reactions 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 ADRs

*: 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.

Description of selected adverse drug reactions

Infections

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.

Malignancies

Lymphoma

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.

Malignancies other than lymphoma

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.

Cases reported in clinical studies in asthma

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.

Neurological events

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.

Liver enzyme elevations

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.

Injection site reactions

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.

Autoimmune antibodies

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%.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

Single doses up to 10 mg/kg intravenously have been administered in a clinical study without dose-limiting toxicity. In case of an overdose, it is recommended that the patient be monitored for any signs or symptoms of adverse effects and appropriate symptomatic treatment be instituted immediately.

Pharmacotherapeutic group: Immunosuppressants, tumour necrosis factor alpha (TNF-α) inhibitors, ATC code: L04AB06

Mechanism of action

Golimumab is a human monoclonal antibody that forms high affinity, stable complexes with both the soluble and transmembrane bioactive forms of human TNF-α, which prevents the binding of TNF-α to its receptors.

Pharmacodynamic effects

The binding of human TNF by golimumab was shown to neutralise TNF-α-induced cell-surface expression of the adhesion molecules E-selectin, vascular cell adhesion molecule (VCAM)-1 and intercellular adhesion molecule (ICAM)-1 by human endothelial cells. In vitro, TNF-induced secretion of interleukin (IL)-6, IL-8 and granulocyte-macrophage colony stimulating factor (GM-CSF) by human endothelial cells was also inhibited by golimumab.

Improvement in C-reactive protein (CRP) levels were observed relative to placebo groups and treatment with Симпони resulted in significant reductions from baseline in serum levels of IL-6, ICAM-1, matrix-metalloproteinase (MMP)-3 and vascular endothelial growth factor (VEGF) compared to control treatment. In addition, levels of TNF-α were reduced in RA and AS patients and levels of IL-8 were reduced in PsA patients. These changes were observed at the first assessment (week 4) after the initial Симпони administration and were generally maintained through week 24.

Clinical efficacy

Rheumatoid arthritis

The efficacy of Симпони was demonstrated in three multi-centre, randomised, double-blind, placebo-controlled studies in over 1500 patients > 18 years of age with moderately to severely active RA diagnosed according to American College of Rheumatology (ACR) criteria for at least 3 months prior to screening. Patients had at least 4 swollen and 4 tender joints. Симпони or placebo were subcutaneously administered every 4 weeks.

GO-FORWARD evaluated 444 patients who had active RA despite a stable dose of at least 15 mg/week of MTX and who had not been previously treated with an anti-TNF agent. Patients were randomised to receive placebo + MTX, Симпони 50 mg + MTX, Симпони 100 mg + MTX or Симпони 100 mg + placebo. Patients receiving placebo + MTX were switched to Симпони 50 mg + MTX after week 24. At week 52, patients entered an open label long-term extension.

GO-AFTER evaluated 445 patients who were previously treated with one or more of the anti-TNF agents adalimumab, etanercept, or infliximab. Patients were randomised to receive placebo, Симпони 50 mg, or Симпони 100 mg. Patients were allowed to continue concomitant DMARD therapy with MTX, sulfasalazine (SSZ), and/or hydroxychloroquine (HCQ) during the study. The stated reasons for discontinuation of prior anti TNF therapies were lack of efficacy (58%), intolerance (13%), and/or reasons other than safety or efficacy (29%, mostly for financial reasons).

GO-BEFORE evaluated 637 patients with active RA who were MTX-naïve and had not previously been treated with an anti-TNF agent. Patients were randomised to receive placebo + MTX, Симпони 50 mg + MTX, Симпони 100 mg + MTX or Симпони 100 mg + placebo. At week 52, patients entered an open label long-term extension in which patients receiving placebo + MTX who had at least 1 tender or swollen joint were switched to Симпони 50 mg + MTX.

In GO-FORWARD, the (co-)primary endpoints were the percentage of patients achieving an ACR 20 response at week 14 and the improvement from baseline in Health Assessment Questionnaire (HAQ) at week 24. In GO-AFTER, the primary endpoint was the percentage of patients achieving an ACR 20 response at week 14. In GO-BEFORE, the co-primary endpoints were the percentage of patients achieving ACR 50 response at week 24 and the change from baseline in the van der Heijde-modified Sharp (vdH-S) score at week 52. In addition to the primary endpoint(s), additional assessments of the impact of Симпони treatment on the signs and symptoms of arthritis, radiographic response, physical function and health-related quality of life were performed.

In general, no clinically meaningful differences in measures of efficacy were observed between the Симпони 50 mg and 100 mg dosing regimens with concomitant MTX, through week 104 in GO-FORWARD and GO-BEFORE and through week 24 in GO-AFTER. In each of the RA studies by study design, patients in the long-term extension may have switched between the 50 mg and 100 mg Симпони doses at the discretion of the study physician.

Signs and symptoms

Key ACR results for the Симпони 50 mg dose at weeks 14, 24 and 52 for GO-FORWARD, GO-AFTER and GO-BEFORE are shown in Table 2 and are described below. Responses were observed at the first assessment (week 4) after the initial Симпони administration.

In GO-FORWARD, among 89 subjects randomised to Симпони 50 mg + MTX, 48 were still on this treatment at week 104. Among those, 40, 33 and 24 patients had ACR 20/50/70 response, respectively at week 104. Among patients remaining in the study and treated with Симпони, similar rates of ACR 20/50/70 response was observed from week 104 through week 256.

In GO-AFTER, the percentage of patients achieving an ACR 20 response was greater for patients receiving Симпони than for patients receiving placebo regardless of the reason reported for discontinuation of one or more prior anti-TNF therapies.

Table 2

Key efficacy outcomes from the controlled portions of GO-FORWARD, GO-AFTER and GO-BEFORE.

^a n reflects randomised patients; actual number of patients evaluable for each endpoint may vary by timepoint.

* p ≤ 0.001

NA: Not Applicable

In GO-BEFORE the primary analysis in patients with moderate to severe rheumatoid arthritis (combined Симпони 50 and 100 mg + MTX groups vs MTX alone for ACR50) was not statistically significant at week 24 (p = 0.053). At week 52 in the overall population, the percentage of patients in the Симпони 50 mg + MTX group who achieved an ACR response was generally higher but not significantly different when compared with MTX alone (see Table 2). Additional analyses were performed in subsets representative of the indicated population of patients with severe, active and progressive RA. A generally greater effect of Симпони 50 mg + MTX versus MTX alone was demonstrated in the indicated population compared with the overall population.

In GO-FORWARD and GO-AFTER, clinically meaningful and statistically significant responses in Disease Activity Scale (DAS)28 were observed at each prespecified time point, at week 14 and at week 24 (p ≤ 0.001). Among patients who remained on the Симпони treatment to which they were randomised at study start, DAS28 responses were maintained through week 104. Among patients remaining in the study and treated with Симпони, DAS28 responses were similar from week 104 through week 256.

In GO-BEFORE, major clinical response, defined as the maintenance of an ACR 70 response over a continuous 6-month period, was measured. At week 52, 15% of patients in the Симпони 50 mg + MTX group achieved a major clinical response compared with 7% of patients in the placebo + MTX group (p = 0.018). Among 159 subjects randomised to Симпони 50 mg + MTX, 96 were still on this treatment at week 104. Among those, 85, 66 and 53 patients had ACR 20/50/70 response, respectively, at week 104. Among patients remaining in the study and treated with Симпони, similar rates of ACR 20/50/70 response were observed from week 104 through week 256.

Radiographic response:

In GO-BEFORE the change from baseline in the vdH-S score, a composite score of structural damage that radiographically measures the number and size of joint erosions and the degree of joint space narrowing in hands/wrists and feet, was used to assess the degree of structural damage. Key results for the Симпони 50 mg dose at week 52 are presented in Table 3.

The number of patients with no new erosions or a change from baseline in total vdH-S Score ≤ 0 was significantly higher in the Симпони treatment group than in the control group (p = 0.003). The radiographic effects observed at week 52 were maintained through week 104. Among patients remaining in the study and treated with Симпони, radiographic effects were similar from week 104 through week 256.

Table 3

Radiographic mean (SD) changes from baseline in total vdH-S score at week 52 in the overall population of GO-BEFORE

^a n reflects randomised patients

* p = 0.015

** p = 0.044

Physical function and health-related quality of life

Physical function and disability were assessed as a separate endpoint in GO-FORWARD and GO-AFTER using the disability index of the HAQ DI. In these studies, Симпони demonstrated clinically meaningful and statistically significant improvement in HAQ DI from baseline versus control at week 24. Among patients who remained on the Симпони treatment to which they were randomised at study start, improvement in HAQ DI was maintained through week 104. Among patients remaining in the study and treated with Симпони, improvement in HAQ DI was similar from week 104 through week 256.

In GO-FORWARD clinically meaningful and statistically significant improvements were demonstrated in health-related quality of life as measured by the physical component score of the SF-36 in patients treated with Симпони versus placebo at week 24. Among patients who remained on the Симпони treatment to which they were randomised at study start, improvement of the SF-36 physical component was maintained through week 104. Among patients remaining in the study and treated with Симпони, improvement of the SF-36 physical component was similar from week 104 through week 256. In GO-FORWARD and GO-AFTER, statistically significant improvements were observed in fatigue as measured by functional assessment of chronic illness therapy-fatigue scale (FACIT-F).

Psoriatic arthritis

The safety and efficacy of Симпони were evaluated in a multi-centre, randomised, double-blind, placebo-controlled study (GO-REVEAL) in 405 adult patients with active PsA (> 3 swollen joints and > 3 tender joints) despite non-steroidal anti-inflammatory (NSAID) or DMARD therapy. Patients in this study had a diagnosis of PsA for at least 6 months and had at least mild psoriatic disease. Patients with each sub-type of psoriatic arthritis were enrolled, including polyarticular arthritis with no rheumatoid nodules (43%), asymmetric peripheral arthritis (30%), distal interphalangeal (DIP) joint arthritis (15%), spondylitis with peripheral arthritis (11%), and arthritis mutilans (1%). Previous treatment with an anti-TNF agent was not allowed. Симпони or placebo were administered subcutaneously every 4 weeks. Patients were randomly assigned to placebo, Симпони 50 mg, or Симпони 100 mg. Patients receiving placebo were switched to Симпони 50 mg after week 24. Patients entered an open label long-term extension at week 52. Approximately forty-eight percent of patients continued on stable doses of methotrexate (≤ 25 mg/week). The co-primary endpoints were the percentage of patients achieving ACR 20 response at week 14 and change from baseline in total PsA modified vdH-S score at week 24.

In general, no clinically meaningful differences in measures of efficacy were observed between the Симпони 50 mg and 100 mg dosing regimens through week 104. By study design, patients in the long-term extension may have switched between the 50 mg and 100 mg Симпони doses at the discretion of the study physician.

Signs and symptoms

Key results for the 50 mg dose at weeks 14 and 24 are shown in table 4 and described below.

Table 4

Key efficacy outcomes from GO-REVEAL

* p < 0.05 for all comparisons;

^a n reflects randomised patients; actual number of patients evaluable for each endpoint may vary by timepoint

^b Psoriasis Area and Severity Index

^c Based on the subset of patients with > 3% BSA involvement at baseline, 79 patients (69.9%) in the placebo group and 109 (74.3%) in the Симпони 50 mg group.

Responses were observed at the first assessment (week 4) after the initial Симпони administration. Similar ACR 20 responses at week 14 were observed in patients with polyarticular arthritis with no rheumatoid nodules and asymmetric peripheral arthritis PsA subtypes. The number of patients with other PsA subtypes was too small to allow meaningful assessment. Responses observed in the Симпони treated groups were similar in patients receiving and not receiving concomitant MTX. Among 146 patients randomised to Симпони 50 mg, 70 were still on this treatment at week 104. Of these 70 patients, 64, 46 and 31 patients had an ACR 20/50/70 response, respectively. Among patients remaining in the study and treated with Симпони, similar rates of ACR 20/50/70 response was observed from week 104 through week 256.

Statistically significant responses in DAS28 were also observed at weeks 14 and 24 (p < 0.05).

At week 24 improvements in parameters of peripheral activity characteristic of psoriatic arthritis (e.g. number of swollen joints, number of painful/tender joints, dactylitis and enthesitis) were seen in the Симпони-treated patients. Симпони treatment resulted in significant improvement in physical function as assessed by HAQ DI, as well as significant improvements in health-related quality of life as measured by the physical and mental component summary scores of the SF-36. Among patients who remained on the Симпони treatment to which they were randomised at study start, DAS28 and HAQ DI responses were maintained through week 104. Among patients remaining in the study and treated with Симпони, DAS28 and HAQ DI responses were similar from week 104 through week 256.

Radiographic response:

Structural damage in both hands and feet was assessed radiographically by the change from baseline in the vdH-S score, modified for PsA by addition of hand distal interphalangeal (DIP) joints.

Симпони 50 mg treatment reduced the rate of progression of peripheral joint damage compared with placebo treatment at week 24 as measured by change from baseline in total modified vdH-S Score (mean ± SD score was 0.27 ± 1.3 in the placebo group compared with -0.16 ± 1.3 in the Симпони group; p = 0.011). Out of 146 patients who were randomised to Симпони 50 mg, 52 week X-ray data were available for 126 patients, of whom 77% showed no progression compared to baseline. At week 104, X-ray data were available for 114 patients, and 77% showed no progression from baseline. Among patients remaining in the study and treated with Симпони, similar rates of patients showed no progression from baseline from week 104 through week 256.

Axial spondyloarthritis

Ankylosing spondylitis

The safety and efficacy of Симпони were evaluated in a multi-centre, randomised, double-blind, placebo-controlled study (GO-RAISE) in 356 adult patients with active ankylosing spondylitis (defined as a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) > 4 and a VAS for total back pain of > 4, on a scale of 0 to 10 cm). Patients enrolled in this study had active disease despite current or previous NSAID or DMARD therapy and had not previously been treated with anti-TNF therapy. Симпони or placebo were administered subcutaneously every 4 weeks. Patients were randomly assigned to placebo, Симпони 50 mg and Симпони 100 mg and were allowed to continue concomitant DMARD therapy (MTX, SSZ and/or HCQ). The primary endpoint was the percentage of patients achieving Ankylosing Spondylitis Assessment Study Group (ASAS) 20 response at week 14. Placebo-controlled efficacy data were collected and analysed through week 24.

Key results for the 50 mg dose are shown in Table 5 and described below. In general, no clinically meaningful differences in measures of efficacy were observed between the Симпони 50 mg and 100 mg dosing regimens through week 24. By study design, patients in the long-term extension may have switched bewtween the 50 mg and 100 mg Симпони doses at the discretion of the study physician.

Table 5

Key efficacy outcomes from GO-RAISE.

* p ≤ 0.001 for all comparisons

^a n reflects randomised patients; actual number of patients evaluable for each endpoint may vary by timepoint

Among patients remaining in the study and treated with Симпони, the proportion of patients with an ASAS 20 and ASAS 40 response were similar from week 24 through week 256.

Statistically significant responses in BASDAI 50, 70 and 90 (p ≤ 0.017) were also seen at weeks 14 and 24. Improvements in key measures of disease activity were observed at the first assessment (week 4) after the initial Симпони administration and were maintained through week 24. Among patients remaining in the study and treated with Симпони, similar rates of change from baseline in BASDAI were observed from week 24 through week 256. Consistent efficacy was seen in patients regardless of use of DMARDs (MTX, sulfasalazine and/or hydroxychloroquine), HLA-B27 antigen status or baseline CRP levels as assessed by ASAS 20 responses at week 14.

Симпони treatment resulted in significant improvements in physical function as assessed by changes from baseline in BASFI at weeks 14 and 24. Health-related quality of life as measured by the physical component score of the SF-36 was also improved significantly at weeks 14 and 24. Among patients remaining in the study and treated with Симпони, improvements in physical function and health-related quality of life were similar from week 24 through week 256.

Non-radiographic axial spondyloarthritis

The safety and efficacy of Симпони were evaluated in a multi-centre, randomised, double-blind, placebo-controlled study (GO-AHEAD) in 197 adult patients with severe active nr-Axial SpA (defined as those patients meeting the ASAS classification criteria of axial spondyloarthritis but did not meet the modified New York criteria for AS). Patients enrolled in this study had active disease (defined as a BASDAI > 4 and a Visual Analogue Scale (VAS) for total back pain of > 4, each on a scale of 0-10 cm) despite current or previous NSAID therapy and had not previously been treated with any biological agents including anti-TNF therapy. Patients were randomly assigned to placebo or Симпони 50 mg administered subcutaneously every 4 weeks. At week 16, patients entered an open label period in which all patients received Симпони 50 mg administered subcutaneously every 4 weeks through week 48 with efficacy assessments performed through week 52 and safety follow-up through week 60. Approximately 93% of patients who were receiving Симпони at the beginning of the open-label extension (week 16) remained on treatment through the end of the study (week 52). Analyses were performed on both the All Treated (AT, N = 197) and Objective Signs of Inflammation (OSI, N = 158, defined by elevated CRP and/or evidence of sacroiliitis on MRI at baseline) populations. Placebo-controlled efficacy data were collected and analysed through week 16. The primary endpoint was the proportion of patients achieving ASAS 20 response at week 16. Key results are shown in Table 6 and described below.

Table 6

Key efficacy outcomes from GO-AHEAD at week 16

Improvements in signs and symptoms

All treated population (AT)

Objective signs of inflammation population (OSI)

Placebo

Симпони 50 mg

Placebo

Симпони 50 mg

na

100

97

80

78

Responders, % of patients

ASAS 20

40%

71%**

38%

77%**

ASAS 40

23%

57%**

23%

60%**

ASAS 5/6

23%

54%**

23%

63%**

ASAS Partial Remission

18%

33%*

19%

35%*

ASDAS-C b < 1.3

13%

33%*

16%

35%*

BASDAI 50

30%

58%**

29%

59%**

Pharmacokinetic properties The information provided in Pharmacokinetic properties of Симпони is based on data of another medicine with exactly the same composition as the Симпони. . Be careful and be sure to specify the information on the section Pharmacokinetic properties in the instructions to the drug Симпони directly from the package or from the pharmacist at the pharmacy. more... Absorption Following a single subcutaneous administration of golimumab to healthy subjects or patients with RA, the median time to reach maximum serum concentrations (Tmax) ranged from 2 to 6 days. A subcutaneous injection of 50 mg golimumab to healthy subjects produced a mean ± standard deviation maximum serum concentration (Cmax) of 3.1 ± 1.4 μg/mL. Following a single subcutaneous injection of 100 mg, the absorption of golimumab was similar in the upper arm, abdomen, and thigh, with a mean absolute bioavailability of 51%. Since golimumab exhibited approximately dose proportional PK following a subcutaneous administration, the absolute bioavailability of a golimumab 50 mg or 200 mg dose is expected to be similar. Distribution Following a single IV administration, the mean volume of distribution was 115 ± 19 mL/kg. Elimination The systemic clearance of golimumab was estimated to be 6.9 ± 2.0 mL/day/kg. Terminal half-life value was estimated to be approximately 12 ± 3 days in healthy subjects and similar values were observed in patients with RA, PsA, AS, or UC. When 50 mg golimumab was administered subcutaneously to patients with RA, PsA or AS every 4 weeks, serum concentrations reached steady state by week 12. With concomitant use of MTX, treatment with 50 mg golimumab subcutaneously every 4 weeks resulted in a mean (± standard deviation) steady-state trough serum concentration of approximately 0.6 ± 0.4 μg/mL in RA patients with active RA despite MTX therapy, and approximately 0.5 ± 0.4 μg/mL in patients with active PsA and approximately 0.8 ± 0.4 μg/mL in patients with AS. Steady-state trough mean serum golimumab concentrations in patients with nr-Axial SpA were similar to those observed in patients with AS following subcutaneous administration of 50 mg golimumab every 4 weeks. Patients with RA, PsA or AS who did not receive concomitant MTX had approximately 30% lower steady-state trough concentrations of golimumab than those who received golimumab with MTX. In a limited number of RA patients treated with subcutaneous golimumab over a 6-month period, concomitant use of MTX reduced the apparent clearance of golimumab by approximately 36%. However, population pharmacokinetic analysis indicated that concomitant use of NSAIDs, oral corticosteroids or sulfasalazine did not influence the apparent clearance of golimumab. Following induction doses of 200 mg and 100 mg golimumab at week 0 and 2, respectively, and maintenance doses of 50 mg or 100 mg golimumab subcutaneously every 4 weeks thereafter to patients with UC, serum golimumab concentrations reached steady state approximately 14 weeks after the start of therapy. Treatment with 50 mg or 100 mg golimumab subcutaneous every 4 weeks during maintenance resulted in a mean steady-state trough serum concentration of approximately 0.9 ± 0.5 μg/mL and 1.8 ± 1.1 μg/mL, respectively. In UC patients treated with 50 mg or 100 mg golimumab subcutaneously every 4 weeks, concomitant use of immunomodulators did not have a substantial effect on steady-state trough levels of golimumab. Patients who developed anti-golimumab antibodies generally had low trough steady-state serum concentrations of golimumab. Linearity Golimumab exhibited approximately dose-proportional pharmacokinetics in patients with RA over the dose range of 0.1 to 10.0 mg/kg following a single intravenous dose. Following a single SC dose in healthy subjects, approximately dose-proportional pharmacokinetics were also observed over a dose range of 50 mg to 400 mg. Effect of weight on pharmacokinetics There was a trend toward higher apparent clearance of golimumab with increasing weight. Pharmacotherapeutic group The information provided in Pharmacotherapeutic group of Симпони is based on data of another medicine with exactly the same composition as the Симпони. . Be careful and be sure to specify the information on the section Pharmacotherapeutic group in the instructions to the drug Симпони directly from the package or from the pharmacist at the pharmacy. more... Immunosuppressants, tumour necrosis factor alpha (TNF-α) inhibitors, ATC code: L04AB06 Preclinical safety data The information provided in Preclinical safety data of Симпони is based on data of another medicine with exactly the same composition as the Симпони. . Be careful and be sure to specify the information on the section Preclinical safety data in the instructions to the drug Симпони directly from the package or from the pharmacist at the pharmacy. more... Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, toxicity to reproduction and development. No mutagenicity studies, animal fertility studies nor long-term carcinogenic studies have been conducted with golimumab. In a fertility and general reproductive function study in mouse, using an analogous antibody that selectively inhibits the functional activity of mouse TNFα, the number of pregnant mice was reduced. It is not known whether this finding was due to effects on the males and/or the females. In a developmental toxicity study conducted in mice following administration of the same analogous antibody, and in cynomolgus monkeys using golimumab, there was no indication of maternal toxicity, embryotoxicity or teratogenicity. Incompatibilities The information provided in Incompatibilities of Симпони is based on data of another medicine with exactly the same composition as the Симпони. . Be careful and be sure to specify the information on the section Incompatibilities in the instructions to the drug Симпони directly from the package or from the pharmacist at the pharmacy. more... In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products. Special precautions for disposal and other handling The information provided in Special precautions for disposal and other handling of Симпони is based on data of another medicine with exactly the same composition as the Симпони. . Be careful and be sure to specify the information on the section Special precautions for disposal and other handling in the instructions to the drug Симпони directly from the package or from the pharmacist at the pharmacy. more... Симпони is supplied in a single use pre-filled pen called SmartJect or as a single use pre-filled syringe. Each Симпони pack is provided with instructions for use that fully describe the use of the pen or the syringe. After removing the pre-filled pen or the pre-filled syringe from the refrigerator it should be allowed to reach room temperature by waiting for 30 minutes, before injecting Симпони. The pen or the syringe should not be shaken. The solution is clear to slightly opalescent, colourless to light yellow and may contain a few small translucent or white particles of protein. This appearance is not unusual for solutions containing protein. Симпони should not be used if the solution is discoloured, cloudy or containing visible foreign particles. Comprehensive instructions for the preparation and administration of Симпони in a pre-filled pen or the pre-filled syringe are given in the package leaflet. Any unused medicinal product or waste material should be disposed of in accordance with local requirements. References: https://www.drugs.com/search.php?searchterm=simponi-rus https://pubmed.ncbi.nlm.nih.gov/?term=simponi-rus Available in countries Russia Find in a country: A B C D E F G H I J K L M N O P Q R S T U V Y Z