Ab0457 jak inhibitors in refractory and at-risk comorbid patients with rheumatoid arthritis in clinical practice

Background The use of JAK inhibitors (JAKi) may be challenged in rheumatoid arthritis (RA) by the multiplicity of previous treatment lines and the presence of comorbidities that may trigger the occurrence of potentially severe side effects. Objectives To assess the efficacy and safety profile of JAKi in active RA patients with refractory disease and/or risk factors for JAKi. Methods Retrospective routine care study carried out between 2018 and 2022 in the Rheumatology department of Cochin Hospital. We selected from our electronic medical report database RA patients initiating a JAKi between 2018 and 2021 who presented active disease (i.e. by a DAS28 >3.2) and at least one of the following criteria: age ≥65 years, presence of comorbidities (cardiovascular risk factors including active smoking, obesity, atherosclerotic cardiovascular (CV) disease, history of venous thromboembolism (VTE), previous malignancy, severe infection including herpes zoster), failure to at least two targeted biological therapies and inability to taper corticosteroids below 7.5 mg/day. Efficacy was assessed at the first visit following the initiation of treatment and at the last available visit up to December 2022. The number and causes of treatment discontinuations were collected during the exposition period. Results We included 83 RA (68 females, 82%) initiating a JAKi, with a mean age of 58 ± 14 years and a mean disease duration of 16 ± 13 years. Patients had a mean DAS28 of 4.60 ± 1.42, they had received 3 ± 2 previous lines of biologics, 63% belonged to the group “age ≥65 years and/or presence of at least one CV risk factor” and 20% received corticosteroids ≥7.5 mg/day. The first treatment visit was scheduled 3 or 6 months following JAKi initiation, and the last visit occurred 15 ± 10 months after the baseline visit. The DAS28 and other parameters assessing disease activity were markedly reduced at the first and the last available visit compared to the baseline visit ( Table 1 ). Low disease activity (DAS28 <3.2) was reached in 51% of patients at the first visit and 47% at the last visit. No difference of efficacy was observed according to the treatment line. A total of 35 patients (42%) discontinued the JAKi during a mean observation period of 20 ± 10 months ( Figure 1 ). The mean time to discontinuation was 10 ± 8 months. Treatment retention was 70% at 12 months and 58% at the last visit. Discontinuations were related to inefficacy (n=21, 25%), side effects (n=11, 13%) and desire for pregnancy (n=3, 4%). The side effects leading to discontinuation were: VTE (n=2), myocardial infarction (n=2) (these 4 events occurred in the group of patients aged ≥65 years with or without presence of at least one CV risk factor), non-severe infections (n=2), allergy (n=2), gastrointestinal symptoms (n=2) and headache (n=1). No cancer was recorded during the observation period. Conclusion In a population o RA enriched with refractory and at-risk comorbid patients, JAKi demonstrated potent efficacy with a safety profile consistent with this population. Our results support the statement from the PRAC to use with caution JAKi in patients aged ≥65 years and/or with at least one CV risk factor. Table 1. Efficacy of JAK inhibitors in D2TRA baseline First visit Last visit Difference First visit-baseline p-value Difference last visit-baseline p-value Tender joints, mean±SD 5.6 ± 5.5 2.7 ± 3.7 2.7 ± 3.9 -2.6 ± 4.8 <0.001 -2.9 ± 5.0 <0.001 Swollen joints, mean±SD 5.4 ± 4.3 2.3 ± 3.4 2.7 ± 4.3 -1.5 ± 3.6 0.002 -1.5 ± 4.2 0.002 VAS pain (/100), mean±SD 59 ± 26 34 ± 22 41 ± 29 -29 ± 27 <0.001 -20 ± 29 <0.001 VAS fatigue (/100), mean±SD 63 ± 28 50 ± 23 52 ± 27 -21 ± 28 <0.001 -13 ± 33 0.040 PGA (/100), mean±SD 61 ± 24 35 ± 22 42 ± 27 -26 ± 28 <0.001 -17 ± 31 <0.001 ESR (mm H1), mean±SD 29 ± 24 27 ± 26 32 ± 29 -2.7 ± 22 0.27 +2.6 ± 29 0.29 CRP (mg/L), mean±SD 9.2 ± 13.1 5.8 ± 13.3 7.72 ± 12.1 -2.7 ± 7.6 0.004 -1.5 ± 1.6 0.071 DAS28, mean±SD 4.60 ± 1.41 3.41 ± 1.59 3.74 ± 1.74 -1.20 ± 1.46 <0.001 -0.79 ± 1.87 0.005 DAS28-CRP, mean±SD 4.06 ± 1.21 2.91 ± 1.17 3.17 ± 1.5 -1.69 ± 1.31 <0.001 -0,77 ± 1.67 <0.001 Figure 1. Time to JAKi discontinuation during the observation period REFERENCES: NIL. Acknowledgements: NIL. Disclosure of Interests Omar Al Tabaa: None declared, Sophie Hecquet: None declared, Marion Thomas: None declared, Sandrine Carvès: None declared, Alice Combier: None declared, Corinne Miceli Richard: None declared, Olivier Fogel: None declared, Anna Moltó: None declared, Yannick Allanore: None declared, Jérôme Avouac Speakers bureau: Abbvie, Galapagos, Lilly, Pfizer, Bristol Myers Squibb, Sanofi, Boehringer, Biogen, Sandoz, MSD, Fresenius Kabi, Novartis, Consultant of: Galapagos, Abbvie, Pfizer, Fresenius Kabi, Sanofi, Grant/research support from: Galapagos, Pfizer, Bristol Myers Squibb, Novartis, Fresenius Kabi.