Adverse events of special interest during the induction
and maintenance studies¹

Immunosuppressive medicinal products

Combination of JYSELECA with other potent immunosuppressants such as ciclosporin, tacrolimus, biologics or other Janus kinase (JAK) inhibitors is not recommended as a risk of additive immunosuppression cannot be excluded.

Infections

Infections, including serious infections, have been reported in patients receiving JYSELECA. The most frequent serious infection reported with JYSELECA was pneumonia. Among opportunistic infections, tuberculosis, oesophageal candidiasis and cryptococcosis were reported with JYSELECA. The risks and benefits of treatment should be considered prior to initiating JYSELECA in patients:

• with chronic or recurrent infection
• who have been exposed to tuberculosis
  
• with a history of a serious or an opportunistic infection
• who have resided or travelled in areas of endemic tuberculosis or endemic mycoses; or
• with underlying conditions that may predispose them to infection.

Patients should be closely monitored for the development of signs and symptoms of infections during and after JYSELECA treatment. If an infection develops during treatment with JYSELECA, the patient should be carefully monitored and JYSELECA treatment should be temporarily interrupted if the patient is not responding to standard antimicrobial therapy. JYSELECA treatment may be resumed once the infection is controlled.

JYSELECA is not recommended in patients with UC who are aged 75 years and older as there are no data in this population.

Tuberculosis

Patients should be screened for tuberculosis before initiating JYSELECA. JYSELECA should not be administered to patients with active tuberculosis. In patients with latent tuberculosis, standard antimycobacterial therapy should be initiated before administering JYSELECA. Patients should be monitored for the development of signs and symptoms of tuberculosis, including patients who tested negative for latent tuberculosis infection prior to initiating treatment.

Viral reactivation

Viral reactivation, including cases of herpes virus reactivation (e.g. herpes zoster), were reported in clinical studies. If a patient develops herpes zoster, JYSELECA treatment should be temporarily interrupted until the episode resolves. Screening for viral hepatitis and monitoring for reactivation should be performed in accordance with clinical guidelines before starting and during treatment with JYSELECA. Patients who were positive for both hepatitis C antibody and hepatitis C virus RNA were excluded from clinical studies. Patients who were positive for hepatitis B surface antigen or hepatitis B virus DNA were excluded from clinical studies.

Malignancy

The risk of malignancies is increased in patients with rheumatoid arthritis and ulcerative colitis. Immunomodulatory medicinal products may increase the risk of malignancies. The clinical data are insufficient to assess the potential incidence of malignancies following exposure to JYSELECA. Long-term safety evaluations are ongoing. Malignancies were observed in clinical studies of JYSELECA. The risks and benefits of JYSELECA treatment should be considered prior to initiating treatment in patients with a known malignancy other than a successfully treated non-melanoma skin cancer (NMSC) or when considering continuing JYSELECA treatment in patients who develop a malignancy.

Non-melanoma skin cancer

NMSCs have been reported in patients treated with JYSELECA. Periodic skin examination is recommended for patients who are at increased risk for skin cancer.

Fertility

In animal studies, decreased fertility, impaired spermatogenesis and histopathological effects on male reproductive organs were observed. The potential effect of JYSELECA on sperm production and male fertility in humans is currently unknown. The reversibility of these potential effects is unknown. The potential risk of reduced fertility or infertility should be discussed with male patients before initiating treatment.

Haematological abnormalities

Absolute neutrophil count (ANC) <1 × 10⁹ cells/L and absolute lymphocyte count (ALC) <0.5 × 10⁹ cells/L were reported in ≤1% of patients in the rheumatoid arthritis clinical studies and in <3% of patients in the ulcerative colitis clinical studies. Treatment should not be initiated, or should be temporarily interrupted, in patients with an ANC <1 × 10⁹ cells/L, ALC <0.5 × 10⁹ cells/L or haemoglobin <8 g/dl observed during routine patient management.

Vaccinations

Use of live vaccines during, or immediately prior to, JYSELECA treatment is not recommended. It is recommended that immunisations be updated in agreement with current immunisation guidelines prior to initiating JYSELECA treatment.

Lipids

Treatment with JYSELECA was associated with dose-dependent increases in lipid parameters, including total cholesterol, and high-density lipoprotein (HDL) levels, while low-density lipoprotein (LDL) levels were slightly increased. LDL cholesterol returned to pre-treatment levels in the majority of patients who started statin therapy while taking JYSELECA. The effect of these lipid parameter elevations on cardiovascular morbidity and mortality has not been determined.

Cardiovascular risk

Patients with rheumatoid arthritis and UC have an increased risk for cardiovascular disorders. JYSELECA should be used with caution in patients with cardiovascular risk factors. Patients should have risk factors (e.g. hypertension, hyperlipidaemia) managed as part of usual standard of care. 

Venous thromboembolism

Events of deep venous thrombosis (DVT) and pulmonary embolism (PE) have been reported in patients receiving JAK inhibitors including JYSELECA. JAK inhibitors should be used with caution in patients with risk factors for DVT/PE, such as older age, obesity, a medical history of DVT/PE, or patients undergoing surgery, and prolonged immobilisation. If clinical features of DVT/PE occur, JYSELECA treatment should be discontinued and patients should be evaluated promptly, followed by appropriate treatment.

Lactose content

Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose–galactose malabsorption should not take this medicinal product.