Simponi, 50 mg/0.5 ml, solution for subcutaneous administration, 0.5 ml, 1 pc.

Simponi 50mg/0.5ml 0.5ml/№1

Infections

Before prescribing Simponi, during therapy and for 5 months after its completion, patients should be closely monitored for the development of infections. If severe infections or sepsis develop, therapy should be discontinued.

Simponi should not be administered to patients with clinically significant active infection. Caution should be exercised when using Simponi in patients with a history of chronic infection or recurrent infection. Patients are advised to avoid exposure to potential risk factors for infection whenever possible.

Patients receiving TNF inhibitor therapy are at greater risk of developing an infectious process. There are reports of the development of bacterial (including sepsis and pneumonia), mycobacterial (tuberculosis), invasive fungal and opportunistic infections, incl. with a fatal outcome in patients receiving TNF inhibitors, including the drug Simponi. In some cases, serious infections have developed in patients receiving concomitant immunosuppressant therapy, which, like the disease itself, predisposes to the development of infections. Patients with new cases of infectious diseases should be carefully assessed. The use of Simponi should be discontinued in cases of severe infections or sepsis and appropriate antibacterial or antifungal therapy should be prescribed until the infection is controlled.

Before initiating treatment with Simponi in patients who have lived in or visited areas where invasive mycoses are endemic, such as histoplasmosis, coccidioidomycosis or blastomycosis, the possible benefits and risks of treatment with Simponi should be carefully weighed.

Tuberculosis

Cases of tuberculosis development have been reported in patients receiving therapy with Simponi. In most cases these were extrapulmonary or disseminated forms of tuberculosis.

Before starting treatment with Simponi, the patient must be carefully examined to identify both active and latent tuberculosis. The examination should include a thorough history taking, incl. it is necessary to exclude a history of tuberculosis and contact with patients with tuberculosis, and also to clarify whether immunosuppressant therapy is currently or has been carried out previously. The necessary screening tests (chest x-ray, tuberculin test) should be performed. It should be taken into account that in seriously ill patients and in patients with immunosuppression, tests for latent tuberculosis may be falsely negative.

If active tuberculosis is diagnosed, therapy with Simponi cannot be started.

If latent tuberculosis is suspected, a phthisiatrician should be consulted.

In all cases described below, the possible risks and expected benefits of therapy with Simponi should be carefully assessed.

In patients with latent tuberculosis, it is necessary to undergo anti-tuberculosis therapy before prescribing Simponi.

In patients with multiple or significant risk factors for developing tuberculosis, but in whom latent tuberculosis is not confirmed by testing, the need for anti-tuberculosis therapy should be considered before initiating therapy with Simponi.

The need for anti-tuberculosis therapy should be considered before initiating treatment with Simponi in patients with a history of active or latent tuberculosis for whom an adequate course of therapy cannot be confirmed.

Cases of the development of active tuberculosis have been reported in patients receiving therapy with Simponi during and after treatment for latent tuberculosis. Patients receiving Simponi should be monitored for signs and symptoms of active tuberculosis, incl. in patients with negative test results for latent tuberculosis, patients receiving therapy for latent tuberculosis, and patients with a history of treatment for tuberculosis.

Patients should be informed about symptoms suspicious for tuberculosis (prolonged cough, weight loss, low-grade fever) and the need to seek medical help if they occur during or after therapy with Simponi.

Hepatitis B virus reactivation

As with treatment with other immunosuppressants, therapy with TNF-α inhibitors was accompanied by reactivation of the hepatitis B virus in chronic carriers of the virus (with a positive test for surface antigen), incl. with the development of death. All patients should be examined to exclude viral hepatitis B before starting therapy. Chronic carriers of the hepatitis B virus should be closely monitored before starting treatment, during treatment and for several months after stopping treatment with Simponi.

Data on the effectiveness of the combined use of antiviral therapy and TNF-α inhibitors in patients who are chronic virus carriers are not available.

If the viral infection reactivates, treatment with Simponi should be discontinued and appropriate antiviral therapy should be prescribed.

Malignant tumors

The possible role of therapy with TNFα inhibitors in the development of malignant tumors has not been established, however, based on current data, the risk of developing lymphomas, leukemia and other malignant tumors during anti-TNFα therapy cannot be excluded. Caution should be exercised when prescribing TNF inhibitors to patients with a history of malignancy or when continuing therapy if a malignancy develops.

Malignant tumors in children

During post-marketing studies, cases of malignancies, some fatal, have been reported among children, adolescents and young adults (<22 years of age) receiving TNF inhibitors (initiation of therapy ≤18 years of age). Lymphoma was reported in approximately half of the cases. Other cases include a range of different malignancies, including malignancies not typically seen in children and adolescents. Most patients received concomitant therapy with immunosuppressants such as methotrexate, azathioprine, or 6-mercaptopurine. The role of TNF inhibitors in the development of malignant tumors in children and adolescents remains unclear.

Lymphoma and leukemia

In controlled clinical trials with all TNF inhibitors, including Simponi, cases of lymphoma were reported more often in patients treated with TNF inhibitors than in the control group. In phase 2b and phase 3 clinical studies, the incidence of lymphoma in patients receiving Simponi was higher than the expected incidence in the general population. Cases of leukemia have been reported during post-marketing use of TNF inhibitors. Because The risk of developing lymphoma and leukemia is increased in patients with rheumatoid arthritis with long-standing, highly active inflammatory disease, and risk assessment is difficult.

In the post-registration period, rare cases of the development of heptolienal T-cell lymphoma have been reported during therapy with TNF inhibitors. This rare type of T-cell lymphoma is very aggressive and usually fatal. Almost all cases have been reported in patients with Crohn's disease or in patients with ulcerative colitis. Most cases have been reported to occur in adolescent or young adult males. Almost all of these patients were treated with azathioprine or 6-mercaptopurine with a TNF inhibitor at or before diagnosis. The possible risk of concomitant use of azathioprine or 6-mercaptopurine and Simponi should be carefully assessed. The risk of developing hepatolienal lymphoma in patients receiving treatment with TNF inhibitors cannot be excluded.

Patients with rheumatoid arthritis and other chronic inflammatory diseases, especially those with high disease activity and/or patients undergoing long-term immunosuppressant therapy, are at several times higher risk of developing lymphoma than in the general population, even without treatment with TNF inhibitors.

Non-lymphocytic malignant tumors

In controlled phase 2b and phase 3 clinical trials of Simponi in patients with rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, and ulcerative colitis, the incidence of other malignancies (excluding nonmelanoma skin cancer) was similar in the Simponi group and the control group.

In clinical

Research results

The patients of all three groups included in the analysis were comparable in age and gender. There were no statistically significant differences in the average time of drug administration from the onset of the disease, the volume of damage to the lung parenchyma, according to CT data, and the content of C-reactive protein before and 24 hours after drug administration (Table 1).

Table 1. Main characteristics of patients in the compared groups

Table 1. The main characteristics of patients in the compared group

* The result is presented as: mean value ± standard deviation.

** The result is presented as the median of the interquartile range.

When analyzing the “Lethal outcome” indicator depending on the drug administered (tocilizumab, olokizumab, levilimab), we were unable to identify significant differences (p = 0.259, Fisher’s exact test for multifield tables) (Table 2). Comparisons of percentages in the analysis of multifield contingency tables were performed using Fisher's exact test. Post hoc comparisons were performed using Pearson's χ2 test with Holm's correction.

Table 2. Analysis of the “Lethal outcome” indicator depending on the administered drug

Table 2. Analysis of the “Lethal outcome” indicator depending on the injected drug

* The percentage is given in parentheses.

When assessing the outcome “Sepsis” depending on the drug administered, we were unable to establish statistically significant differences (p = 0.587, Fisher’s exact test for multi-field tables) (Table 3). As a quantitative measure of the effect when comparing relative indicators, we used the OR indicator with a 95% confidence interval (95% CI).

Table 3. Analysis of the “Sepsis” indicator depending on the drug administered

Table 3. Analysis of the “Sepsis” indicator depending on the injected drug

An analysis of the Sepsis indicator was carried out depending on the subcutaneous or intravenous administration of tocilizumab (Table 4). When assessing the Sepsis indicator depending on the route of administration of tocilizumab, it was not possible to detect statistically significant differences (p = 0.293, Fisher's exact test). The odds of sepsis in the subcutaneous tocilizumab group were 2.28 times lower compared with the intravenous tocilizumab group, and the odds difference was not statistically significant (OR = 0.44; 95% CI 0.1–1.88). When assessing the “Lethal outcome” indicator depending on the route of administration, it was not possible to identify statistically significant differences (p = 0.279, Fisher’s exact test). The odds of dying in the subcutaneous group were 1.85 times lower compared to the intravenous group, and the difference in odds was not statistically significant (OR = 0.54; 95% CI 0.18–1.62) (Table 5).

Table 4. Analysis of the Sepsis indicator depending on the route of administration of tocilizumab

Table 4. Analysis of the “Sepsis” indicator depending on the way of injected drug tocilizumab

Table 5. Analysis of the “Lethal outcome” indicator depending on the route of administration of tocilizumab

Table 5. Analysis of the indicator “Lethal outcome” depending on way of injection tocilizumab