TY - JOUR
T1 - JAK inhibitors and the risk of malignancy
T2 - a meta-analysis across disease indications
AU - Russell, Mark D.
AU - Stovin, Christopher
AU - Alveyn, Edward
AU - Adeyemi, Olukemi
AU - Chan, Chun Kit David
AU - Patel, Vishit
AU - Adas, Maryam A.
AU - Atzeni, Fabiola
AU - Ng, Kenrick K.H.
AU - Rutherford, Andrew I.
AU - Norton, Sam
AU - Cope, Andrew P.
AU - Galloway, James B.
N1 - Funding Information:
JG has acted in an advisory role to many pharmaceutical companies (listed below), including to provide specific advice on malignancy risk with JAK inhibition for the purpose of regulatory review. He received no funding for this systematic review and meta-analysis, and there was no industry involvement or oversight for any stage of this project. JG has received honoraria from AbbVie, Biovitrum, BMS, Celgene, Chugai, Galapagos, Gilead, Janssen, Lilly, Novartis, Pfizer, Roche, Sanofi, Sobi and UCB. MDR has received honoraria from Lilly, Galapagos, Biogen and Menarini, and support for attending meetings from Lilly, Pfizer, Janssen and UCB. APC has received grant funding from BMS, and consulting fees from BMS, AbbVie and GSK/Galvini.
Funding Information:
MDR is funded by a National Institute for Health Research (NIHR) Doctoral Fellowship (NIHR300967).
Publisher Copyright:
© 2023 BMJ Publishing Group. All rights reserved.
PY - 2023/8/1
Y1 - 2023/8/1
N2 - Objectives To estimate the association of Janus kinase inhibitors (JAKi) with the incidence of malignancy, compared with placebo, tumour necrosis factor (TNF)-α inhibitors (TNFi) and methotrexate. Methods Systematic searches of databases were performed, to December 2022, to identify phase II/III/IV randomised clinical trials (RCTs) and long-term extension (LTE) studies of JAKi (tofacitinib, baricitinib, upadacitinib, filgotinib, peficitinib) compared with placebo, TNFi or methotrexate, in adults with rheumatoid arthritis, psoriatic arthritis, psoriasis, axial spondyloarthritis, inflammatory bowel disease or atopic dermatitis. Network and pairwise meta-analyses were performed to estimate incidence rate ratios (IRRs) for malignancy between JAKi and comparators. Bias was assessed using the Cochrane Risk of Bias-2 tool. Results In 62 eligible RCTs and 16 LTE studies, there were 82 366 person-years of exposure to JAKi, 2924 to placebo, 7909 to TNFi and 1074 to methotrexate. The overall malignancy incidence rate was 1.15 per 100 person-years in RCTs, and 1.26 per 100 person-years across combined RCT and LTE data. In network meta-analyses, the incidence of all malignancies including non-melanomatous skin cancers (NMSCs) was not significantly different between JAKi and placebo (IRR 0.71; 95% CI 0.44 to 1.15) or between JAKi and methotrexate (IRR 0.77; 95% CI 0.35 to 1.68). Compared with TNFi, however, JAKi were associated with an increased incidence of malignancy (IRR 1.50; 95% CI 1.16 to 1.94). Findings were consistent when analysing NMSC only and when analysing combined RCT/LTE data. Conclusions JAKi were associated with a higher incidence of malignancy compared with TNFi but not placebo or methotrexate. Cancers were rare events in all comparisons. PROSPERO registration number CRD42022362630.
AB - Objectives To estimate the association of Janus kinase inhibitors (JAKi) with the incidence of malignancy, compared with placebo, tumour necrosis factor (TNF)-α inhibitors (TNFi) and methotrexate. Methods Systematic searches of databases were performed, to December 2022, to identify phase II/III/IV randomised clinical trials (RCTs) and long-term extension (LTE) studies of JAKi (tofacitinib, baricitinib, upadacitinib, filgotinib, peficitinib) compared with placebo, TNFi or methotrexate, in adults with rheumatoid arthritis, psoriatic arthritis, psoriasis, axial spondyloarthritis, inflammatory bowel disease or atopic dermatitis. Network and pairwise meta-analyses were performed to estimate incidence rate ratios (IRRs) for malignancy between JAKi and comparators. Bias was assessed using the Cochrane Risk of Bias-2 tool. Results In 62 eligible RCTs and 16 LTE studies, there were 82 366 person-years of exposure to JAKi, 2924 to placebo, 7909 to TNFi and 1074 to methotrexate. The overall malignancy incidence rate was 1.15 per 100 person-years in RCTs, and 1.26 per 100 person-years across combined RCT and LTE data. In network meta-analyses, the incidence of all malignancies including non-melanomatous skin cancers (NMSCs) was not significantly different between JAKi and placebo (IRR 0.71; 95% CI 0.44 to 1.15) or between JAKi and methotrexate (IRR 0.77; 95% CI 0.35 to 1.68). Compared with TNFi, however, JAKi were associated with an increased incidence of malignancy (IRR 1.50; 95% CI 1.16 to 1.94). Findings were consistent when analysing NMSC only and when analysing combined RCT/LTE data. Conclusions JAKi were associated with a higher incidence of malignancy compared with TNFi but not placebo or methotrexate. Cancers were rare events in all comparisons. PROSPERO registration number CRD42022362630.
KW - arthritis, psoriatic
KW - arthritis, rheumatoid
KW - biological therapy
KW - epidemiology
KW - spondylitis, ankylosing
UR - http://www.scopus.com/inward/record.url?scp=85164393487&partnerID=8YFLogxK
U2 - 10.1136/ard-2023-224049
DO - 10.1136/ard-2023-224049
M3 - Article
C2 - 37247942
AN - SCOPUS:85164393487
SN - 0003-4967
VL - 82
SP - 1059
EP - 1067
JO - Annals of the rheumatic diseases
JF - Annals of the rheumatic diseases
IS - 8
ER -