OA08 JAK inhibitors and the risk of malignancy: a meta-analysis across licenced disease indications

Abstract

Abstract Background/Aims Concerns have been raised about the risk of malignancy with Janus kinase inhibitors (JAKi) following the ORAL Surveillance study, which reported an increased incidence of malignancy with tofacitinib compared with Tumor Necrosis Factor-α inhibitors (TNFi) in people with rheumatoid arthritis (RA) aged over 50 years who had additional cardiovascular risk factors. Our objective was to estimate the risk of malignancy for all licenced JAKi across disease indications, compared with TNFi, methotrexate (MTX), and placebo. Methods A systematic search of electronic databases (Medline, EMBASE, Cochrane) was performed to identify Phase 2/3/4 RCTs and long-term extension (LTE) studies of JAKi (tofacitinib, baricitinib, upadacitinib, filgotinib, peficitinib) in adults with RA, psoriatic arthritis, psoriasis, axial spondyloarthritis, inflammatory bowel disease, or atopic dermatitis. Comparators were placebo, MTX, and TNFi. Random-effects meta-analysis was performed to compare malignancy incidence rates between JAKi and comparators. Our primary outcome measure was the incidence of all malignancies including non-melanomatous skin cancers (NMSC). Secondary outcomes were malignancies excluding NMSC, and NMSC only. Results In 62 eligible RCTs and 14 LTE studies, there were 71,767 person-years of exposure to JAKi; 2,680 to placebo; 7,827 to TNFi; and 1,074 to MTX. Comparing JAKi with placebo arms of RCTs, the incidence rate ratio (RR) for all malignancies including NMSC was not significantly different (RR 0.81; 95% CI 0.52 to 1.26; p = 0.36). Similarly, when comparing JAKi with MTX, no significant differences were observed in the incidence of malignancy (RR 0.73; 95% CI 0.33 to 1.61; p = 0.43). Compared with TNFi, however, administration of JAKi was associated with an increased incidence of malignancy (RR 1.54; 95% CI 1.19 to 2.01; p = 0.001). For all analyses, findings were consistent when excluding NMSC, when analysing NMSC only, and when including LTE data. Conclusion In trial settings, JAKi do not associate with an increased risk of malignancy compared with placebo or MTX, but are associated with an increased risk of malignancy relative to TNFi. Disclosure C. Stovin: None. M.D. Russell: Honoraria; Lilly, Galapagos, Biogen, Menarini. Other; Lilly, Pfizer, Janssen, UCB. E. Alveyn: None. O. Adeyemi: None. V. Patel: None. M.A. Adas: None. F. Atzeni: None. K.K.H. Ng: None. A.I. Rutherford: None. S. Norton: None. A.P. Cope: Consultancies; BMS, Abbvie, GSK/Galvini. Grants/research support; BMS. J.B. Galloway: Honoraria; Abbvie, Biovitrum, BMS, Celgene, Chugai, Gilead, Janssen, Lilly, Novartis, Pfizer, Roche, Sanofi, Sobi, UCB.