Tofacitinib

Inhibition of the selective activation of JAK1/JAK2 or JAK1/JAK3 and blockade of the intracellular signalling cascade of the JAK-STAT signalling pathway. This results in the blockade of signal transduction by interleukins 2, 4, 6, 7, 9, 15 and 21, as well as type I and type II interferons, resulting in a reduction in the inflammatory response.

Adults with active psoriatic arthritis treated in combination with a conventional synthetic DMARD who have previously shown an inadequate response to a DMARD or have been unable to tolerate the medication.

Psoriasis vulgaris: off-label.

No

Treatment of adult patients with active psoriatic arthritis in combination with a conventional synthetic DMARD to improve symptoms and physical function in patients who had responded inadequately to, or were unable to tolerate, previous treatment with a DMARD.

Complete blood count (CBC), liver enzymes, lipid profile, creatinine, urinalysis, pregnancy test, CRP, screening for HBV, HCV, HIV and TB (optionally including chest X-ray), update of vaccination status (including varicella/herpes zoster vaccination).

Complete blood count (CBC), CRP, transaminases, creatinine, β-hCG; lipid levels.

Month 1, 2, then every 3 months; lipid levels: month 2, then every 6 months.

Oral tablets: 5 mg, 10 mg.

5 mg 1-0-1; may be increased to 10 mg 1-0-1; at 20 mg daily, there is an increased risk of thromboembolic events.

After days or weeks.

Known diverticulitis (CAUTION: bowel perforation); no vaccinations with live vaccines immediately before or during treatment with JAK inhibitors; in cases of moderate renal impairment, do not exceed a dose of 1 × 5 mg per day (for the indications of psoriatic arthritis or rheumatoid arthritis).

In cases of moderate hepatic impairment, do not exceed a dose of 5 mg of tofacitinib once daily (indicated for psoriatic arthritis or rheumatoid arthritis).

Caution is advised, particularly in patients over 65 years of age or in patients with increased risk factors for malignancies.
Hormonal contraception or hormone replacement therapy, risk factors for thromboembolic events, patients with malignancies, congenital coagulation disorders, major surgery.

12,110 (2 × 5 mg daily)

19,918 (2 × 10 mg daily)

Neoplasms, infections, neutropenia < 0.5 × 10⁹/L (= 1 G/L) (dose reduction from < 1 × 10⁹/L (= 1 G/L)), haemoglobin < 80 g/L or a decrease of > 20 g/L, lymphopenia < 0.5 × 10⁹/L (= 1 G/L); in patients with psoriatic arthritis and moderate hepatic impairment, reduce the dose to 5 mg/day.

After 12 weeks.

Insufficient data.

Hypersensitivity to the relevant JAK inhibitor or to excipients; severe progressive or opportunistic infection; severe hepatic impairment (Child-Pugh Class C); neutropenia < 1 x 10⁹ (= 1 G/L); hormonal contraception or hormone replacement therapy; anaemia < 90 g/L, lymphopenia < 0.5 × 10⁹/L (= 1 G/L), pregnancy and breastfeeding (teratogenic effects have been observed in animal studies), thromboembolic events, congenital coagulation disorders, patients with malignancies, major surgery, anaemia < 80 g/L, severe renal impairment (GFR < 30 ml/min), heart failure.

Infections (e.g. nasopharyngitis, urinary tract infection, bronchitis, influenza, pneumonia, sinusitis, etc.), viral infections (e.g. herpes zoster, viral gastroenteritis), bacterial infections (e.g. pyelonephritis, bacteraemia), malignant diseases (e.g. solid tumours, non-melanoma skin cancer, lymphomas), anaemia, leucopenia, hyperlipidaemia, weight gain, insomnia, headache, hypertension, diarrhoea, nausea, abdominal pain, rash, arthralgia, increased blood creatine phosphokinase levels, musculoskeletal pain, elevated liver enzymes, fever, fatigue, thrombosis/embolism (particularly at doses >10 mg), gastrointestinal perforation, fractures.

Cases of reactivation of HBV infection have been reported.

Do not initiate treatment in patients with chronic hepatitis B. Patients who are carriers of the hepatitis B virus and require treatment with tofacitinib must be closely monitored for symptoms of reactivated HBV infection throughout the entire course of treatment and for several months after the end of treatment.
In the event of HBV reactivation, treatment with tofacitinib must be discontinued and effective antiviral therapy, together with appropriate supportive care, must be initiated.

Data insufficient; no reactivation of the virus has been reported to date.

Treatment with tofacitinib should not be initiated in the presence of a chronic hepatitis C infection.

Insufficient data.

Cyclosporine, CYP3A4 inducers (e.g. rifampicin), OCT substrates (e.g. chloroquine); in the case of potent inhibitors of CYP3A4 (such as ketoconazole, itraconazole, voriconazole) or CYP2C19 (e.g. fluconazole), the dose of Xeljanz should be reduced to 5 mg/day; no interactions with MTX or biologics have been reported (however, use is not recommended).

Testing prior to initiation; anti-tuberculosis treatment should be considered in patients with a history of latent or active TB and unclear treatment history, as well as in patients with a negative test result for latent TB who have risk factors; in cases of latent TB, standard anti-mycobacterial therapy should be administered.

Treatment with isoniazid and vitamin B6 is required for 9 months; treatment with biologics may be started after 1 month. Alternatively, rifampicin for 4 months.

Malignant diseases have been observed in clinical trials and during post-authorisation use (including lung cancer, lymphomas, breast cancer, melanoma, prostate cancer and pancreatic cancer). A dose-dependent increase in cases of non-melanoma skin cancer (NMSC) has been observed.