FRI0028 JAK2 MUTATION MAY PREDICT RESPONSE AND GUIDE FIRST LINE TREATMENT IN RHEUMATOID ARTHRITIS
Authors: Y. Adel Abdelsalam Hussein, Y. Sadeq, M. Sabry
Journal: Annals of the Rheumatic Diseases (2020)

Background: JAK2 mutation found to be associated with the myeloproiferative disorders [1] with possibility of measurement in blood by PCR [2] . There are many interesting parallels between the CTDs and MPDs [3] . STAT4 is activated by the JAK members as JAK2 in response to IL and TNF, with subsequent down-stream signaling for autoimmunity [4] . JAK inhibitors are medications function by inhibiting activity of Janus kinase enzymes and have therapeutic application in treatment of cancer and rheumatoid arthritis [5] . Objectives: Impact of pretreatment JAK2 mutation on response to first line csDMARDS in RA. Methods: 76 newly diagnosed RA patients and 50 matched controls were included. Pretreatment JAK2 mutation was measured in serum by PCR with TNF-α and IL 6 were assessed by ELISA in patients and controls. All patients started treatment by conventional synthetic DMARDs (including methotrexate). Response assessment at 3 rd month was evaluated by DAS28 and ACR response criteria. JAK2 mutation was correlated with different clinical and laboratory parameters of patients. Results: 62 females (81.6%) and 14 males (18.4%) with age mean ± SD; (48.8 ± 7.3). Pretreatment JAK2 mutation, TNF-α and IL 6 were significantly high in patients. JAK2 mutation was detected in 39 (51.3%) patients while 37 (48.7%) patients were JAK2 non mutant. Mutant JAK2 was significantly associated with severity of disease assessed by DAS28; 14 (70%) of patients with DAS28 (≤2.6) were non mutant JAK2 versus sex (30%) patients mutant JAK2 while 13 (76.5%) of patients with DAS28 (&gt;5.1) were mutant JAK2 versus four (23.5%) patients non mutant JAK2 (P 0.03), table1 . JAK2 mutation found to be significantly correlated with ACR 20, 50 and 70 response criteria; 40% of patients with non mutant JAK2 showed ACR 70 versus 17.9% in mutant group, 35.1% of patients with non mutant JAK2 showed ACR 50 versus 30.8% in mutant group while 24.3% of patients with non mutant JAK2 showed ACR 20 versus 51.3% in mutant group (P 0.02), table1 . JAK2 mutation was associated with high pretreatment TNFα (mean±SD; 41.7±39.5 in mutant versus 24.3±23.04 pg/ml in non mutant group) with P (0.04), while no significant relation between JAK2 mutation and pretreatment IL6 level. Conclusion: Adult SLE with pretreatment JAK2 mutation significantly showed high disease activity, high pretreatment TNFα level and poor response to 1st line csDMARDs including MTX so they could get benefit with introduction of JAK inhibitors as first line mono or in combination with csDMARDS especially those with moderate to severe active RA. References: [1]Koppikar, P. and R.L. Levine, JAK2 and MPL mutations in myeloproliferative neoplasms. Acta Haematol, 2008. 119 (4): p. 218-25. [2]Baxter, E.J., et al., Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders. Lancet, 2005. 365 (9464): p. 1054-61. [3]McQueen, F.M. and N. Dalbeth, Will Jill come tumbling after? The case for a JAK2-type mutation as a prequel to the connective tissue disorders. Med Hypotheses, 2009. 73 (5): p. 651-4. [4]Watford, W.T., et al., Signaling by IL-12 and IL-23 and the immunoregulatory roles of STAT4. Immunol Rev, 2004. 202 : p. 139-56. [5]Norman, P., Selective JAK inhibitors in development for rheumatoid arthritis. Expert Opin Investig Drugs, 2014. 23 (8): p. 1067-77. Table 1. JAK2 mutation with disease activity and response criteria. DAS28 Non Mutant JAK2 Mutant JAK2 X P Remission (≤ 2.6) 14 (70%) 6 (30%) 8.6 0.03 Low disease activity (≤ 3.2) 13 (54.2%) 11 (45.8%) Moderate disease activity (3.2 - 5.1) 6 (40%) 9 (60%) Sever disease activity (&gt;5.1) 4 (23.5%) 13 (76.5%) ACR Non Mutant JAK2 Mutant JAK2 ACR 20 9 (24.3%) 20 (51.3%) 7.0 0.02 ACR 50 13 (35.1%) 12 (30.8%) ACR 70 15 (40.5%) 7 (17.9%) Disclosure of Interests: None declared