Cimzia

[Drug name]

Trade name: Ximinjia

Common name: Certolizumab Pegol Iniection

English name: Certolizumab Pegol Iniection

[Indications]

This product is used in combination with methotrexate (MIX) for:

Treatment of anti-wind drugs that improve the condition ( Adult patients with moderately to severely active rheumatoid arthritis (RA) who cannot respond to DMARDS) (including MTX). When combined with MTX, it can slow down the progression of joint damage in patients (X-ray detection) and improve physical function.

[Ximinjia Adverse Reactions]

Rheumatoid Arthritis

Ximinjia conducted controlled and open trials on 4,049 patients with rheumatoid arthritis for up to 92 months. The data in Table 1 are mainly based on placebo-controlled studies, which included a total of 2965 patients taking Ciminga and 1137 patients taking placebo during the control period.

In placebo-controlled studies, the duration of exposure in patients treated with Ciminjia was approximately 4 times longer than in the placebo control group. The difference in exposure was primarily due to patients in the placebo group being more likely to drop out early. In addition, in the RA-I and RA-II studies, non-responders were forced to withdraw at week 16, most of whom were from the placebo group.

In controlled studies, the proportion of patients who discontinued treatment due to adverse events was: 4.4% of patients treated with pescilizumab and 2.7% of patients treated with placebo.

According to system organ ## organ classification, the most common adverse reactions are as follows: infection and infestation, the incidence rate of patients in the peslkizumab group was 14.4%, and the incidence rate of patients in the placebo group was 8.0%; systemic abnormalities and administration site Discomfort, the incidence rate was 8.8% in the peslkizumab group, and 7.4% in the placebo group; skin and subcutaneous tissue abnormalities, the incidence rate was 7.0% in the peslkizumab group, and 2.4% in the placebo group. List of Adverse Reactions

Table 1 below lists the adverse reactions that are at least potentially related to Ciminjia in clinical trials and post-marketing reports of pescelizumab in rheumatoid arthritis according to frequency and system organ ##organ classification. Frequency classification is as follows: very common (≥1/10); common (≥1/100 to <1/10); rare (≥1/1000 to <1/100); rare (≥1/10,000 to <1/1000); very rare (<1/10,000), unknown (cannot be evaluated based on available data). Within each frequency category, adverse reactions are ranked in order of decreasing severity.

Adverse reactions (occasionally) observed with Ximinjia in other indications include gastrointestinal stenosis and occlusion, deterioration of general health, spontaneous abortion and azoospermia.

Some adverse reactions indicate infection

In placebo-controlled clinical trials of rheumatoid arthritis, the new infection rate among patients treated with Ciminjia was 1.03/patient-year, and the rate in the placebo control group was 0.92/patient-year. Infections mainly include upper respiratory tract infection, urinary tract infection, lower respiratory tract infection and herpes virus infection (see [Contraindications] and [Precautions]).

In placebo-controlled clinical trials, there were more new cases of serious infections in the Cimrezumab treatment group (0.07/patient-year; all doses) compared with placebo (0.02/patient-year). Frequent serious infections include pneumonia and tuberculosis infections. Serious infections also include infections with invasive opportunistic pathogens (eg, pneumocystis, fungal esophagitis, nocardiosis, and disseminated herpes zoster). There is no evidence that prolonged drug exposure increases the risk of infection (see Precautions).

Malignant Neoplasms and Lymphoproliferative Disorders

In clinical trials of rheumatoid arthritis that included 4049 patients (representing 9,277/patient-years), 121 malignancies, including 5 lymphomas, were observed in addition to cutaneous non-melanomas. In the CIMJA rheumatoid arthritis clinical trial, the incidence rate of lymphoma was 0.05/100 patient-years and the incidence rate of melanoma was 0.08/100 patient-years (see [Precautions]).

Autoimmunity

In the pivotal clinical study, 16.7% of subjects with negative baseline antinuclear antibodies (ANA) developed positive ANA titers after treatment with Ciminga, compared with 12.0% of subjects in the placebo group. Among subjects with negative anti-double-stranded DNA (anti-dsDNA) antibodies at baseline, 2.2% showed positive anti-dsDNA antibody titers after treatment with Ciminjia, compared with 1.0% in the placebo control group. Occasional cases of lupus-like syndrome have been reported in both placebo-controlled and open follow-up clinical trials of rheumatoid arthritis. Other immune-mediated disorders have been rarely reported; their association with Cimja is unclear. The impact of long-term use of Ciminga on the development of autoimmune diseases is unknown.

Injection site reactions

In the placebo Liuzhao rheumatoid arthritis clinical study, 5.8% of patients treated with pescilizumab experienced injection site reactions, such as erythema, itching, hematoma, pain, swelling or bruising, and the incidence rate in the placebo group was 4.8%. The incidence of injection site pain was 1.5% among patients treated with Ciminja, but no cases were withdrawn from clinical trials as a result.

Reporting suspected adverse reactions

It is important to report suspected adverse reactions after approval of a medical product. This allows continued monitoring of the benefit/risk ratio of medical products. Healthcare professionals should report any suspected adverse reactions through the appropriate national reporting system.

[Ximinjia Contraindications]

It is prohibited for those who are allergic to Ximinjia ingredients or any excipients.

Contraindicated in patients with active tuberculosis or other serious infections, such as sepsis or opportunistic infections (see [Precautions]).

Contraindicated in patients with moderate to severe heart failure (NYHA grade IIIV) (see [Precautions]).

[Ximinjia Precautions]

Infection

Patients must be closely monitored for symptoms and signs of infection, including tuberculosis, before, during and after treatment with Ximinjia. Because absorption of pescilizumab takes 5 months to clear, monitoring should be performed during this period (see Contraindications).

If a patient develops clinically significant active infection, regardless of chronic or local infection, treatment with Ximinjia should not be started until the infection is under control (see [Contraindications]).

During treatment with Ximinjia, patients should be closely monitored if they develop new infections. When a patient develops a new serious infection, treatment with Ciminjia should be stopped until the infection is under control. For patients with a history of recurrent or opportunistic infections or patients with underlying conditions that predispose them to infection, including concurrent use of immunosuppressants, physicians should carefully consider the use of Ximinjia treatment.

Due to the disease and concomitant use of medical products, patients with rheumatoid arthritis may not experience typical symptoms of infection such as fever. Therefore, early detection of any infection, especially the detection of atypical clinical manifestations of severe infections, is crucial to reduce missed diagnosis and prompt treatment.

Severe infections, including sepsis and tuberculosis (including miliary, disseminated, and extrapulmonary tuberculosis), and opportunistic infections (such as histoplasmosis, nocardiosis, candidiasis) have been reported with the use of CIMINDIA. Some of these conditions are fatal.

Tuberculosis

All patients must be evaluated for active or inactive (latent) tuberculosis infection before starting treatment with Ciminga. This assessment should include the patient's detailed history of tuberculosis, previous contact with patients with active tuberculosis, and previous and/or current immunosuppressive therapy. Appropriate screening tests such as tuberculin skin testing and chest X-ray must be performed on all patients (refer to local recommendations). Prescribers should consider that tuberculin skin tests can give false negative results, especially in seriously ill or immunocompromised patients.

If active tuberculosis is diagnosed before or during treatment, treatment with Ciminjia must not be used or treatment must be stopped (see [Contraindications]).

If inactive ("latent") tuberculosis is suspected, a professional physician with experience in tuberculosis treatment should be consulted. For the following situations, the benefits and risks of treatment with Ciminjia need to be carefully weighed.

If latent tuberculosis is diagnosed, appropriate anti-tuberculosis treatment must be initiated according to local treatment guidelines before using Ciminga.

For patients with a history of latent or active tuberculosis but it is not possible to confirm whether they have received an adequate course of anti-tuberculosis treatment, and for patients with obvious risk of tuberculosis infection but negative latent tuberculosis test results, anti-tuberculosis treatment should be considered before using Ximinjia. If there is any possibility of latent tuberculosis infection, biological testing for tuberculosis screening should be considered before starting treatment with Bacillus Calmette-Guérin (BCG), regardless of previous vaccination.

Cases of active tuberculosis have been reported in patients treated with TNF antagonists (including Ciminja), even if they were previously or currently taking anti-tuberculosis prophylaxis. Some patients with active tuberculosis who had been successfully treated experienced recurrence of tuberculosis during treatment with this drug.

During or after treatment with Ximinjia, if the patient develops symptoms of suspected tuberculosis infection (such as persistent cough, weight loss/weight loss, low-grade fever, and fatigue), the patient should be advised to seek medical treatment immediately. Hepatitis B virus (HBV) reactivation

Reactivation of hepatitis B may occur in chronic carriers of hepatitis B virus (e.g., surface antigen positive) who receive TNF antagonist treatment including Ciminja, and some cases have fatal outcomes.

An examination for HBV infection should be performed before starting treatment with Ximinjia. For patients who are positive for HBY infection, it is recommended to consult a professional physician who treats hepatitis B.

HBV carriers who receive treatment with Ximinjia should be closely monitored for signs and symptoms of active HBV infection during treatment and for several months after treatment ends. There are insufficient data to prove that combined TNF antagonist therapy can prevent HBV reactivation in HBV carriers receiving antiviral therapy. Patients with HBV reactivation should discontinue treatment with Ciminga and initiate antiviral therapy with appropriate supportive care.

Malignant tumors and lymphoproliferative diseases

The potential role of INF node antagonist therapy in the development of malignant tumors is unclear. Caution should be exercised when considering the use of TNE antagonists in patients with a history of malignant tumor pain or when considering continued treatment in patients with malignant tumors.

Based on current knowledge, the risk of lymphoma, leukemia or other malignant tumors cannot be ruled out in patients receiving TNF antagonist therapy.

In clinical trials of TINF antagonists and other INF antagonists, more cases of lymphoma and other malignancies occurred in patients treated with TINF antagonists than in patients treated with placebo (see [Adverse Reactions]). Based on post-marketing data, leukemia has been reported in patients taking TNE antagonists. Patients with rheumatoid arthritis who have long-term, highly active inflammatory disease have a higher background risk for lymphoma and leukemia, further complicating risk assessment.

Studies on continuing the treatment of patients with a history of cancer or patients with new cancer have not yet been carried out.

Skin Cancer

Melanoma and Merkel cell carcinoma have been reported in patients treated with TNF antagonists, including Criminx (see Adverse Reactions). Regular skin examinations are recommended, especially for patients with risk factors for skin cancer.

Pediatric Malignancies

Based on post-marketing data, malignancies, some of which are fatal, have been reported in children, adolescents (≤18 years of age at initiation of treatment), and young adults (up to 22 years of age) taking TNF antagonists. Nearly half of these are lymphomas. A variety of other malignancies have also been reported, including rare malignancies typically associated with immunosuppression. The risk of malignancy in children and adolescents treated with TNF antagonists cannot be excluded.

After the marketing of TNF antagonists, there were reports of patients developing hepatosplenic T-cell lymphoma (HSTCL). This rare type of T-cell lymphoma has an aggressive course and is often fatal. Cases reported using TNF antagonists mostly occur in adolescents and young adult males with Crohn's disease or ulcerative colitis. Almost all of these patients were treated with the immunosuppressants azathioprine and mercaptopurine in addition to TNR antagonists at or before diagnosis. The risk of hepatosplenic T-cell lymphoma in patients taking Ciminjia cannot be ruled out.

Chronic obstructive pulmonary disease (COPD)

In an exploratory clinical study evaluating the use of another TNF antagonist, infliximab, in patients with moderate to severe chronic obstructive pulmonary disease (COPD), patients in the infliximab treatment group had more malignant tumors than those in the control group, mostly in the lungs or head and neck. All patients had a history of heavy smoking. Therefore, prescribers should carefully consider prescribing TNF antagonists in patients with COPD and those at increased risk of malignancy due to heavy smoking.

Congestive heart failure

Patients with moderate to severe heart failure are prohibited from using Ximinjia (see [Contraindications]). In another clinical trial of a TNF antagonist, exacerbation of congestive heart failure and an increase in deaths due to congestive heart failure were observed. Congestive heart failure has also been reported in patients receiving Ciminga for the treatment of rheumatoid arthritis. Ximinjia should be used with caution in mild heart failure (NYHA class II). Patients treated with Ciminga must stop taking the drug if they develop new or worsening symptoms of congestive heart failure.

Hematological reactions

Pancytopenia, including aplastic anemia, has been reported rarely in patients receiving TNF antagonists. There have also been reports of hematological adverse reactions during the use of Ciminjia, including clinically significant cytopenias (such as leukopenia, pancytopenia, and thrombocytopenia) (see [Adverse Reactions]). Patients who develop blood disorders or signs and symptoms of infection (eg, persistent fever, bruising, bleeding, pale skin) should be diagnosed and treated immediately. For those patients with confirmed hematological abnormalities, Ximinjia should be discontinued immediately.

Neurological Events

The use of TNF antagonists has rarely been associated with the development or worsening of demyelinating lesions, including multiple sclerosis, in terms of clinical symptoms and/or radiographic findings. For patients with past or recent demyelinating lesions, physicians should carefully consider the benefits and risks of TNF antagonists before treating Ziminjia. There are rare reports of neurological abnormalities such as seizures, neuritis, and peripheral neuropathy in patients treated with Ziminjia. Allergic Reactions

There have been rare reports of serious allergic reactions after using Ximinjia. Some of these reactions have occurred after administration of Ciminga. If a serious reaction occurs, Ximinjia should be discontinued immediately and appropriate treatment measures should be taken.

There are very limited data on patients taking Ciminjia due to severe allergies to other TNF antagonists; special caution should be used in these patients.

Immunosuppression

Because TNF can mediate inflammation and regulate cellular immune responses, TNF antagonists (including Ximinjia) may cause immunosuppression, thereby affecting the body's fight against infections and malignant tumors.

Auto-rabbit disease

Treatment with Ximinjia may lead to the production of ANA, but the occurrence of lupus-like syndrome is rare (see [Adverse Reactions]). The effects of long-term use of Ciminga on autoimmune diseases are unknown. If a patient develops suspicious symptoms of lupus-like syndrome after treatment with Ciminga, the medication must be discontinued. Ximinjia has not been studied in people with lupus (see Adverse Reactions).

Vaccination

In addition to live vaccines, patients using Ximinjia can receive vaccinations at the same time. There are no data showing that patients taking Ciminja respond to live vaccines or that secondary infections are transmitted due to live vaccines. Live vaccines cannot be used at the same time as Ximinjia.

In a placebo-controlled clinical trial in patients with rheumatoid arthritis, when pneumococcal polysaccharide vaccine and influenza vaccine were administered at the same time, the antibody response of the Ciminjia group was similar to that of the placebo group. The level of humoral response was lower in patients who received the combination of Ciminja and MTX than in patients who took Ciminja alone. Its clinical significance is unclear.

Combined use with other biological agents

Serious infections and neutropenia have been reported in clinical studies in which anakinra (an interleukin-1 antagonist) or abataceptr (a CD28 modulator) was combined with another TNF antagonist, etanercept, and the combination did not improve efficacy compared with the TNF antagonist alone. Based on the adverse reaction profile seen when another TNF antagonist is used in combination with abatacept or anakinra, similar toxicities may occur when anakinra or abatacept is used in combination with other TNF antagonists. Therefore, concomitant use of Ciminja with other biologic antirheumatic drugs (such as anakinra or abatacept) or other TNF antagonists is not recommended (see Drug Interactions). Surgery Experience with surgery in patients treated with Ciminga is limited. When planning surgery in patients, the half-life of Ciminga should be considered to be 14 days. When surgery is required for patients treated with Ciminka, infection should be closely monitored and appropriate measures taken.

Activated partial thromboplastin time (aPTT) analysis

Ximinjia will interfere with certain coagulation function tests in patients, and thus may cause falsely elevated aPTT test results in patients without coagulation abnormalities. This result was observed with DiagnosticaStago's PTT-lupus anticoagulant (LA) test and the standard targeted activated partial prothrombin time (STA-PTT) automated test, Instrumentation Laboratories' HemosILAPTT-SP liquid, and the HemosIL lyophilized silicon content assay. Other aPTT analyzes may be similarly affected. There is no evidence that treatment with CIMJA affects blood clotting in the body. After patients take Ximinjia, they should be cautious in interpreting abnormal coagulation results. No effects on thrombin time (TT) and prothrombin time (PT) measurements have been observed.

Elderly patients

In clinical trials, despite limited experience, the incidence of infection was significantly higher in patients aged 65 and older compared with younger subjects. Caution should be used when administering medication to elderly patients, and special attention should be paid to the occurrence of infection.

Effects on the ability to drive and operate machinery

Ximinjia may have a slight effect on the ability to drive and operate machinery. Dizziness (including vertigo, visual impairment and fatigue) may occur after using Ximinjia (see [Adverse Reactions]).

Special precautions for disposal and other operations

Ximinjia is for one-time use only. All unused product or waste should be disposed of in accordance with local requirements.