Ab0363 safety of Jak Inhibitors in Patients With Arthritis Rheumatoid Under Real-Life Conditions

Abstract

Background:Efficacy and safety profile of new JAK inhibitors have been properly defined by several clinical trials, being tested in many patients with Arthritis Reumatoid. However, real-life conditions studies play an important role in order to know JAK inhibitors behaviour in safety.Objectives:To describe adverse events of JAK inhibitors in patients with Arthritis Rheumatoid and asses the survival in relation to adverse events.Methods:Observational, descriptive, retrospective design performed in patients with Arthritis Reumatoid in follow-up by the Rheumatology department of the Hospital de Valme until January 2019. Demographic and clinical data related to safety has been collectedResults:58 patients were included with a mean age of 57,77 ± 10,78 years. Mean time from diagnosis was 8,7 ± 6,54 years, female predominance (75%). Mean ASDAS at the beginningof JAK inhibitor treatment was 4,76 ± 0,93. Regarding the determination of FR and CCCP 69% and was positive in both cases. Baricitinib was the treatment chosen in 13 patients (22.4%), and Tofacitinib in 45 patients (77.6%). Regarding associated treatments: 84.5% was under low-dose steroids theraphy; 77.6% was under combined therapy with at least 1 DMARD; 15.5% with two of them. Metotrexato was used in 53,4% of patients, leflunomide in 19%, hydroxycloroquine in 13.8%, sulfasalazyne in 12.1%. 72,4% have been before under at least one biologic treatment (frequently antiTNF), 41,1% one of them, 15.5% two of them, 12.1% three and 1.7% four before starting Jak inhibitor therapy. Adverse events has been observed in 17 patients (13 from de Tofacitinib group -28.8%-, and 4 in the Baricitinib group -30.76%). The most common advers events were: herpes zoster infections (4 patients in Tofacitinib group), respiratory infections (3), urinary infections (2), cutaneous (3), caphalea (1), legs oedema (2), toxic hepatitis in 1 patient of Baricitinib group; pulmonary thromboembolism was observed in 1 patient of Tofacitinib group, and atrial fibrillation in other patients of that group. Treatment was interrupted in 24 of 58 patients (mean time 8.92 ± 5.14 months), 16 from Tofacitinib group (35.5% of patients with Tofacitinib) and 8 from Baricitinib group (61.15% of patients with Tofacitinib). In Tofacitinib group, 10 patients stopped therapy for inefficacy reasons and 6 for advers effects related. In Baricitinib group, 5 due to inefficacy, 2 to adverse effects and 1 to clinical remission.Conclusion:Main adverse effect were mild-moderate infections (involving in-hospital treatment only in one Barictinib group patient). One pulmonary thromboembolism has been detected in a hypertensive 70 years old patient, supporting the recent recommendation of avoiding these drugs in patients over 65 or with cardiovascular risk factors. It is remarkable low survival results due to inefficacy, that could be related to clinical profile of refractory patients in our study, and/or to the small sample that we describe.Disclosure of Interests:None declared

Real-world evidence of tofacitinib in rheumatoid arthritis patients in Spain

“…In the Spanish population, the study with the most extended follow-up of survival was from Soleto et al (45) which showed promising results with tofacitinib at 12 months. The frequency of interruption of treatment due to ineffectiveness is noteworthy, which could be related to refractory patients' clinical profile in the studies and/ or the small sample used (47). The most commonly reported AE in retrospective studies among the Spanish population was HZ infection (45,58), which is in line with results by Kremer et al (31) in the US, where the 5-year incidence rate of AEs was evaluated.…”

“…Between 2019 and 2021, 16 retrospective studies reported the tofacitinib experience in patients with RA on routine clinical practice in Spain (38)(39)(40)(41)(42)(43)(44)(45)(46)(47)(48)(49)(50)(51)(52)(53). Data from case-series were obtained from medical records and databases of a hospital's Rheumatology Service (Supplementary Table S1, http://www.ddtjournal.com/ action/getSupplementalData.php?ID=94).…”

“…Another study revealed a median survival of 35 months for patients receiving tofacitinib (50). Regarding the percentages of follow-up, one study showed 66.6% (6/9) (46) of patients remaining on treatment with tofacitinib, and another study showed 64.4% (29/45) (47).…”

“…Related to the occurrence of AEs, studies reported the percentage of AEs as between 15.0% (6/40) (39) and 39.0% (11/28) (43). The most frequent AEs in each study included: infections (68/122, 55.7%) (53), hypercholesterolemia (5/9, 55.5%) (46), and herpes zoster (HZ), with the latter being the most repeated AE throughout the studies, representing between 3.3% (4/122) (53) and 30.8% (4/13) of cases (47). Infections reported in several of the studies were respiratory infections 33.3% (2/6), odontogenic infections 16.7% (1/6) (39) and infections in general 69.7% (46/66).…”

“…Similar to other real-world series (US Corrona registry, Canadian registry) (32,33), tofacitinib is administered as monotherapy in a considerable percentage of patients (between 20% to 67.9%). Concerning combined therapy, the most frequently used csDMARD was MTX (39,41), and in the case of corticosteroid application, the doses were low (47). In Spain, some retrospective studies have compared the efficacy and safety of JAK inhibitors under real-world conditions, obtaining similar results (37,38,41).…”