Adverse events of special interest during the induction
and maintenance studies¹

GI, gastrointestinal; HZ, herpes zoster; NMSC, non-melanoma skin cancer; PE, pulmonary embolism; UC, ulcerative colitis.

References: 1. Feagan BG, Danese S, Loftus EV Jr, et al. Lancet 2021;397:2372–2384.

Most commonly reported adverse events

HZ, herpes zoster.

JYSELECA should only be used if no suitable treatment alternatives are available in:

• Patients 65 years of age and older
• Patients with history of atherosclerotic cardiovascular disease or other cardiovascular risk factors (such as current or past long-time smokers)
• Patients with malignancy risk factors (e.g. current malignancy or history of malignancy)

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.

As there is a higher incidence of infections in the elderly and in the diabetic populations in general, caution should be used when treating the elderly and patients with diabetes. In patients 65 years of age and older, JYSELECA should only be used if no suitable treatment alternatives are available.

Tuberculosis

Patients should be screened for tuberculosis before initiating JYSELECA, and 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. In rheumatoid arthritis clinical studies, the risk of herpes zoster appeared to be higher in female patients, Asian patients, patients ≥50 years of age, patients with a medical history of herpes zoster, patients with a medical history of chronic lung disease and patients treated with JYSELECA 200 mg once daily. 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

Lymphoma and other malignancies have been reported in patients receiving JAK inhibitors, including JYSELECA. In a large randomised active-controlled study of tofacitinib (another JAK inhibitor) in rheumatoid arthritis patients 50 years and older with at least one additional cardiovascular risk factor, a higher rate of malignancies, particularly lung cancer, lymphoma and nonmelanoma skin cancer (NMSC) was observed with tofacitinib compared to TNF inhibitors. In patients 65 years of age and older, patients who are current or past long-time smokers, or with other malignancy risk factors (e.g. current malignancy or history of malignancy), JYSELECA should only be used if no suitable treatment alternatives are available.

Non-melanoma skin cancer (NMSC)

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

Haematological abnormalities

Do not start therapy, or temporarily stop, if absolute neutrophil count (ANC) <1 × 10⁹ cells/l, absolute lymphocyte count (ALC) <0.5 × 10⁹ cells/l or haemoglobin <8 g/dl. Temporarily stop therapy if these values are 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, including prophylactic zoster vaccinations, 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 highdensity 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.

Major adverse cardiovascular events (MACE)

Events of MACE have been observed in patients taking JYSELECA. In a large randomised active-controlled study of tofacitinib (another JAK inhibitor) in rheumatoid arthritis patients 50 years and older with at least one additional cardiovascular risk factor, a higher rate of major adverse cardiovascular events (MACE), defined as cardiovascular death, non-fatal myocardial infarction (MI) and non-fatal stroke, was observed with tofacitinib compared to TNF inhibitors. Therefore, in patients 65 years of age and older, patients who are current or past long-time smokers, and patients with history of atherosclerotic cardiovascular disease or other cardiovascular risk factors, JYSELECA should only be used if no suitable treatment alternatives are available.

Venous thromboembolism (VTE)

Events of deep venous thrombosis (DVT) and pulmonary embolism (PE) have been reported in patients receiving JAK inhibitors including JYSELECA. In a large randomised active-controlled study of tofacitinib (another JAK inhibitor) in rheumatoid arthritis patients 50 years and older with at least one additional cardiovascular risk factor, a dose dependent higher rate of VTE including deep venous thrombosis (DVT) and pulmonary embolism (PE) was observed with tofacitinib compared to TNF inhibitors. In patients with cardiovascular or malignancy risk factors, JYSELECA should only be used if no suitable treatment alternatives are available. In patients with known VTE risk factors other than cardiovascular or malignancy risk factors, JYSELECA should be used with caution. VTE risk factors other than cardiovascular or malignancy risk factors include previous VTE, patients undergoing major surgery, immobilisation, use of combined hormonal contraceptives or hormone replacement therapy, inherited coagulation disorder. Patients should be re-evaluated periodically during JYSELECA treatment to assess for changes in VTE risk. Promptly evaluate patients with signs and symptoms of VTE and discontinue JYSELECA in patients with suspected VTE, regardless of dose.

Use in patients over 65 years of age

Considering the increased risk of MACE, malignancies, serious infections, and all-cause mortality in patients 65 years of age and older, as observed in a large randomised study of tofacitinib (another JAK inhibitor), JYSELECA should only be used in these patients if no suitable treatment alternatives are available.

Lactose content

Contains lactose; patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose galactose malabsorption should not take JYSELECA.

Pregnancy/lactation

JYSELECA is contraindicated in pregnancy. JYSELECA should not be used during breast-feeding. Women of childbearing potential must use effective contraception during and for at least 1 week after cessation of treatment.

Driving/using machinery

No or negligible influence, however dizziness and vertigo have been reported during treatment with JYSELECA.