AB0352 CONSENSUS STATEMENT: USE OF JAKINIB THERAPY IN IMMUNE MEDIATED INFLAMMATORY DISEASES.

Abstract

Background:Janus kinase inhibitor therapy is approved for use in a variety of Immune mediated inflammatory diseases.Objectives:With 4 agents approved & 1 in development, it is timely to undertake a systematic literature review (SLR) of evidence across indications for efficacy, safety & management issues.Methods:Existing data was evaluated by a steering committee & subsequently by a 25 person expert committee leading to a consensus statement to assist the clinician once the decision had been made to commence a Jakinib. The Committee included patients, rheumatologists, gastroenterologist, haematologist, dermatologist & infectious disease specialists. SLR of Medline, Embase, Cochrane, abstracts from 2018 EULAR & ACR congresses & Epistemonikos identified 1,178 RA & PsA, 128 SLE, & 1339 “other indications” unique references meeting criteria that included randomized & open label clinical trials, registries, phase 4 trials, & meta-analyses. Warnings from regulators issued after the end of the SLR search date were taken into consideration. Cochrane risk of bias tool was used.Results:General principles included (1) shared decision making, (2) adherence to T2T principles, (3) reference to disease specific product information & (4) reference to country/region specific treatment algorithms. Mode of action & indications are discussed & consensus was reached on pre-treatment screening, contra-indications, monitoring, treatment dose, co-medications & adverse effects (see Table 1.), with 80-100% agreement. A research agenda was formulated to update the review as new information becomes available.Table 1.Baseline characteristics of the patients1. Patient history, examination2. Routine Laboratory testing: FBC diff LFTs Renal function, lipids at wk 123. Hepatitis Bs Ag & Ab, core Ab & Hep C ab, & HIV in high risk individuals.4.TB screening as per national guidelines5.Assess & update vaccination status6.Consider VTE risk factors – prior history, familial VTE, use of Cox2 inhibitorsB. Monitoring1. FBC diff LFTs mth 1, & mth 3 with lipids, repeat periodically2. Annual skin examination3. Evaluated response using validated disease specific measures of disease activity – be aware ESR/CRP may be reduced independently of reduction in disease activity or infectionC. Contra-indications (consult label & warnings)1. Severe active (or chronic) infection, including tuberculosis and opportunist infections2. Current malignancies3.Pregnancy & lactation4. Severe organ dysfunction eg severe hepatic disease (Child-Pugh C) or severe renal disease5. Allergy to Jak ihibitor6. History of VTE (relative contra-indication, careful consideration +/_ anticoagulation)Table.Peripheral blood cell counts for each week.D. Adverse Effects.1. Serious infections including opportunist infections, TB, Herpes Zoster, are increased. The risk is lowered with reduction or elimination of concomitant corticosteroid2.Rates of malignancy do not appear elevated although the risk of NMSC may be elevated3. Lymphopenia, neutropenia, elevated liver transaminases, & lipid changes have been noted4. An increased risk of VTE has been reported in a safety trial of tofacitinib & in the placebo-controlled trial period of baricitinib in RA patients5. Elevations of CPK noted but have been rarely associated with clinical events6. Elevations of creatinine noted but not associated with renal failure or hypertensionConclusion:The consensus provides an assessment of evidence for efficacy & safety of an important therapeutic class with guidance on practical management issues.Acknowledgments:Unrestricted grants were provided by Abbvie & Lilly with no input into the planning & development of the recommendations, nor influence or attendance at the meeting nor review of the abstract, with full disclosures from participants & the opportunity to declare any feelings of conflict of interest.Disclosure of Interests:Peter Nash Grant/research support from: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Gilead, Janssen, MSD, Novartis, Pfizer Inc, Roche, Sanofi, UCB, Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Gilead, Janssen, MSD, Novartis, Pfizer Inc, Roche, Sanofi, UCB, Speakers bureau: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Gilead, Janssen, MSD, Novartis, Pfizer Inc, Roche, Sanofi, UCB, Andreas Kerschbaumer Paid instructor for: Celgene, Speakers bureau: Andreas Kerschbaumer has received lecture fees from Bristol-Myers Squibb, Gilead, Merck Sharp and Dohme and Pfizer., Désirée van der Heijde Consultant of: AbbVie, Amgen, Astellas, AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Cyxone, Daiichi, Eisai, Eli-Lilly, Galapagos, Gilead Sciences, Inc., Glaxo-Smith-Kline, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda, UCB Pharma; Director of Imaging Rheumatology BV, Josef S. Smolen Grant/research support from: AbbVie, AstraZeneca, Celgene, Celltrion, Chugai, Eli Lilly, Gilead, ILTOO, Janssen, Novartis-Sandoz, Pfizer Inc, Samsung, Sanofi, Consultant of: AbbVie, AstraZeneca, Celgene, Celltrion, Chugai, Eli Lilly, Gilead, ILTOO, Janssen, Novartis-Sandoz, Pfizer Inc, Samsung, Sanofi