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About JAKi Experience  JAKi Market Experience XELJANZ Mechanism of Action Efficacy and Safety Clinical Efficacy RA Rapid Data (ACR20) Head-to-Head Noninferiority Data (ACR50) Clinical Efficacy PsA ACR20 Data PASI75 Data Enthesitis and Dactylitis Data Clinical Efficacy UC 8-Week Efficacy Onset of Action Data 52-Week Efficacy OCTAVE Study Design Safety and Tolerability Safety in RA Safety in PsA Safety in UC Dosing and Administration Dosing in RA Dosing Practical Considerations Dosing in PsA Dosing Practical Considerations Dosing in UC Dosing Practical Considerations Resources and Support Resources and Support eXel ProgramEventsMaterials Videos
Safety in UC1-4The safety profile for XELJANZ® was studied across 3 large placebo-controlled phase 3 clinical trials (2 induction and 1 maintenance), and an open-label safety and tolerability study, with 2440.8 patient-years of exposure.2Adverse reactions

  • In the induction and maintenance studies across all treatment groups, the most common types of serious adverse reactions were gastrointestinal disorders and infections, and the most common serious adverse reaction was worsening of UC2

  • <5% of patients in any of the XELJANZ or placebo treatment groups in the induction and maintenance studies discontinued because of adverse events (excluding patients with worsening UC)2

The rates of the 4 most frequent adverse events occurring in the maintenance trial are listed for the 3 placebo-controlled trials, and the rates of the most frequently reported treatment related adverse events are reported for the open-label extension study.2,4Pooled UC studies (phases 2-3 and OLE)Predominant dose in the overall cohort (including patients in Phase II, III, and OLE studies) as of May 2019.5Limitations of overall cohort and open-label extension (OLE) data

  • Pooled, post hoc analysis of studies from the UC clinical trial program are subject to certain limitations. First, unlike ORAL Surveillance, the patient population is not limited to a high-risk population but includes all enrolled patients. Second, endpoints of interest (such as MACE and malignancy for ORAL Surveillance) were not specifically defined and adjudicated. Additionally, ORAL Surveillance was a long-term safety study (vs. shorter term and designed to test efficacy). Resultant incidence rates in ORAL Surveillance differed from rates seen from pooled study data, suggesting the pooled data may be obscuring information about predictors of events given adverse rates may differ from one patient population to another and may change over time

  • OLE studies may provide useful data, however, conduct of OLE studies where both treatment and dose are known to both investigator and patient is subject to certain biases and limitations

  • Biases include, but are not limited to, patient selection (patient willingness or ineligibility to enroll, which may be due to a prior serious AE), prior treatment, volunteer, observer, initial dose or study drug, investigator/patient expectation and study duration. Limitations include, but are not limited to, AE frequencies and incidence rates subject to change over time due to patient entry/exit, dose changes influenced by both investigator and patient, dose restrictions in certain countries, the number of patients and exposure for a specific safety event possibly differing depending on the timing of censored events, and the number of observed patients with longer exposure times becoming lower

AEs of Special Interest in the XELJANZ UC Trials

  • In the long-term extension study, malignancies (including solid cancers, lymphomas, and NMSC) were observed more often in patients treated with XELJANZ 10 mg BID4

Hepatic impairment

  • XELJANZ should not be used in patients with severe hepatic impairment3

Use in pregnancy

  • XELJANZ should not be used during pregnancy or by women attempting to become pregnant. Women of reproductive potential should be advised to use effective contraception both during treatment with XELJANZ and after discontinuing therapy.3 

  • The extended pharmacodynamic effects of XELJANZ should be considered when determining how long to continue effective contraception after discontinuing XELJANZ therapy.3 

Venous thromboembolism (VTE)

 

  •  

  • In a large randomised PASS, increased incidence of thrombosis (including pulmonary embolism [PE], deep vein thrombosis [DVT] and arterial thrombosis) and of all-cause mortality (including sudden cardiovascular [CV] death) have been observed in patients with RA who were 50 years of age or older, particularly in patients who were obese (BMI ≥30), with at least one additional CV risk factor treated with XELJANZ 10 mg BID* compared to XELJANZ 5 mg BID or TNF blockers.Assess patients for thrombotic risk factors before starting treatment and periodically during treatment.

  • Avoid XELJANZ in elderly patients and in patients who may be at increased risk of thrombosis or in whom other risk factors are identified.

  • Discontinue XELJANZ and promptly evaluate patients with signs and symptoms of thrombosis, regardless of dose or indication. For the treatment of UC, use XELJANZ at the lowest effective dose and for the shortest duration needed to achieve/maintaintherapeutic response.

  • Advise your patients to seek medical attention immediately if these signs and symptoms occur.*XELJANZ 10 mg BID is not approved for the treatment of RA in Australia

  •  

Major Adverse Cardiovascular Events (MACE) and Malignancies

  • In a large randomised PASS in RA patients who were 50 years or older with at least one additional cardiovascular risk factor, an increase in non-fatal myocardial infarctions was observed in patients treated with XELJANZ compared to TNF inhibitor.

  • MACE (including events of myocardial infarction) were more common in patients who were older and patients who were current or past smokers 1,3 

    • Caution should be used in treating elderly patients, patients who are current or past smokers, and patients with other malignancy risk factors. Consider the risks and benefits of continuing XELJANZ treatment in patients who develop a malignancy.3

ORAL Surveillance (Study A3921133)1,2

In a Phase IIIb/IV randomized, open-label, non-inferiority, postauthorization safety, endpoint-driven study among patients 50 years of age or older with moderate to severe RA, with at least one additional CV risk factor and taking MTX without adequate control of symptoms:

  • The coprimary endpoints were adjudicated MACEa and adjudicated malignancies (excluding NMSC)

  • For adjudicated MACE and adjudicated malignancies (excluding NMSC), the prespecified noninferiority criterion was not met for the primary comparison of the combined tofacitinib doses to TNFib

For more information on the ORAL Surveillance study, click here.Example TextMACE defined as cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke.​​​​​​​The noninferiority criterion was not met for the primary comparison of the combined tofacitinib doses to TNF-alpha inhibitors since the upper limit of the 95% CI exceeded the prescribed noninferiority criterion of 1.8 (ie, for MACE: 1.94>1.8, for malignancy: 2.09>1.8).10​​​​​​​Explore more Learn about the oral administration of XELJANZ See recommended dosing BID=twice daily; BMI=body mass index; CI=confidence interval; CV=cardiovascular; DVT=deep vein thrombosis; GI=gastrointestinal; JAKi=Janus kinase inhibitor; MACE=major adverse cardiovascular event; MTX=methotrexate; NMSC=non-melanoma skin cancer; OLE=open-label extension; PD=predominant dose; PE=pulmonary embolism; 
pt-yr=patient years; QD=once a day; RA=rheumatoid arthritis; SD=standard deviation; TNFi=tumor necrosis factor inhibitor; UC=ulcerative colitis; VTE=venous thromboembolism.Safety and Tolerability
EFFICACY

See pivotal data in active UC

 See UC data
EXPERIENCE

Find out more about the JAKi with the longest market experience in RA, PsA, and UC

 See XELJANZ Experience
References:Ytterberg SR, Bhatt DL, Mikuls TR, et al; for the ORAL Surveillance Investigators. Cardiovascular and cancer risk with tofacitinib in rheumatoid arthritis. N Engl J Med. 2022;386(4):316-326.Sandborn WJ, Lawendy N, Danese S, et al. Safety and efficacy of tofacitinib for treatment of ulcerative colitis: final analysis of OCTAVE Open, an open-label, long-term extension study with up to 7.0 years of treatment. Aliment Pharmacol Ther. 2021; 00:1-15.XELJANZ Approved Product InformationWinthrop KL, Loftus EV, Baumgart DC, et al. Tofacitinib for the Treatment of Ulcerative Colitis: Analysis of Infection Rates from the Ulcerative Colitis Clinical Programme. J Crohns Colitis. 2020;15(6):914-929. Suppl:1-20.Vermeire S, Armuzzi A, Kwok KK, et al. The effect of tofacitinib on serum lipids and cardiovascular safety in patients with ulcerative colitis: results from the tofacitinib OCTAVE ulcerative colitis clinical program. Field report 538 presented at: Digestive Disease Week Virtual (DDW); May 21-23, 2021.Lichtenstein GR, Rogler G, Ciorba MA, et al. Tofacitinib, an oral Janus kinase inhibitor: analysis of malignancy (excluding nonmelanoma skin cancer) events across the ulcerative colitis clinical program. Inflamm Bowel Dis. 2021.27;(6):816-825.Sandborn WJ, Panés J, Sands BE, et al. Incidence of venous thromboembolic events in patients with ulcerative colitis treated with tofacitinib in the ulcerative colitis clinical programme: an update as of May 2019. Poster P598 presented at: Congress of the European Crohn’s and Colitis Organisation (ECCO); 12-15 February 2020; Vienna, Austria.

▼This medicinal product is subject to additional monitoring in Australia. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse events at www.tga.gov.au/reporting-problems.

WARNINGS 
XELJANZ should only be used if no suitable treatment alternatives are available in patients: 
  • with history of atherosclerotic cardiovascular disease or other cardiovascular risk factors (such as current or past, long-time smokers) 
  • with malignancy risk factors (e.g. current malignancy or history of malignancy) 
  • who are 65 years of age and older. 

See PI for details, Section 4.4 Special Warnings and Precautions for Use: Mortality; Major Adverse Cardiovascular Events (including Myocardial Infarction); Thrombosis; Malignancy and Lymphoproliferative Disorder (excluding Nonmelanoma Skin Cancer [NMSC]); Skin Cancer and Use in the Elderly. 


Before prescribing, please review full Product Information available here.
 

PBS Information: Authority required for the treatment of adults with severe active rheumatoid arthritis and for adults with severe psoriatic arthritis and for adults with moderate-to-severe ulcerative colitis. Refer to the PBS Schedule for full authority information. This product is not listed on the PBS for juvenile idiopathic arthritis, juvenile psoriatic arthritis, or ankylosing spondylitis.

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