Ab1339-Hpr safety and Adherence of the Jak Inhibitors in Clinical Practice in Rheumatoid Arthritis

Abstract

Background:The Janus Kinase (JAKi) inhibitors Baricitinib (BAR) and Tofacitinib (TOF) are indicated for moderate to severe active rheumatoid arthritis (RA). Data about safety, effectiveness in refractory patients and adherence in real clinical practice in our population are scarce.Objectives:An evaluation of safety, adherence and reasons to consider suspension of JAKi in routine clinical practice.Methods:Retrospective observational study of patients with RA treated with BAR and TOF according to usual clinical practice between September 2017 - December 2019. Data were collected from the electronic medical record and from the Dominion® Outpatient Drug Dispensing program.Demographic, clinical, laboratory and treatment-related variables were collected, including reasons for discontinuing JAKi (inefficiency and toxicity). Adherence was calculated using the Compliance Questionnaire on Rheumatology (CQR-5), and the average possession ratio (RMP), which is defined as the number of days with treatment dispensed between the total days of the period analyzed, considering the adherent patient when RMP had a ≥ 0.8.Laboratory abnormalities were defined according to normal limit values (NLV) and specifications of data sheet. A descriptive analysis was performed using proportions, medians and interquartile ranges (IQR) using the SPSS v.15 program.Results:Thirty patients were included in treatment with BAR and nine with TOF. The median age was 62.9 (RIQ 49.9-74.4), 34 (87.2%) were women, 28 (71.2%) anti-CCP and 32 (82.1%) were rheumatoid factor positive, with erosive disease in 34 (87,2%) patients. In the previous treatment, 9 (23.1%) were naive to biological, 6 (15.4%) had received 1 biological, 18 (46.1%) 2 biologicals, and 6 (15.4%) ≥ 3 biologicals. The median treatment time was 8.4 months (RIQ 6.5-20.3) in BAR and 13.2 (RIQ 3.9-20.7) in TOF.The reasons for consider suspension shown in Table 1.Table 1.Treatment DiscontinuationBARICITINIBInitial DAS28[median (IQR)]Final DAS28[median (IQR)]Continue treatmentn (%): 17/30 (55.6)4.20 (2.95-5.72)2.60 (1.70-2.77)Reasons for suspension-Refractory n (%): 7/13 (55.8%)4.38 (4.16-5.43)4,16 (3.56-5.23)-Side effects n (%): 4/13 (30.7)4.16 (3.45-4.84)3.15 (2.69-4.41) ◦Thrombocytosis (1) ◦Herpes Zoster (1) ◦Anemia (1) ◦Tubaritis (1)-Patient decisión n (%): 2/13 (15.4)TOFACITINIBContinue treatmentn (%): 6/9 (66.6)4.82 (3.28-6.20)2.61 (2.45-3.70)Reasons for suspension-Refractory n (%): 2/3 (66.6)5.27 (5.23-5.31)5.48 (5.04-5.92)-Side effects n (%): 1/3 (33.33)Based on the CQR5 questionnaire, all patients treated with BAR and TOF were adherent “HIGH” class, and a median of RMP = 1.01 (IQR = 0.93-1.06) was obtained for BAR and RMP = 1, 00 (IQR = 0.91-1.01) for TOF, all adherents (≥ 0.8).Table 2.Safety results of the treatment shows the safety results.Side EffectBaricitinib(n, %)Tofacitinib(n, %)Hb <11 g/dl7 (23,3)0Hb < 8 g/dl0 (0)/Hb Recovery >11 g/dl2/7 (28,6)/Neutrophils < 1500/mm30 (0)/Lymphocytes < 1000/mm33 (10,0)2 (22,2)Platelets > 600 × 103/mm31 (3,3)0AST o ALT > 1 NLV4 (13.3)0 (0)Hypercholesterolemia (> 1 NLV)13 (43.3)5 (55.5)Infections13 (43.3)0 (0)Herpes zoster6 (20,0)0 (0)Conclusion:In our population, mostly refractory to biological, more than half of the patients maintain treatment with JAKi, with optimal adherence. The main reason for the suspension of both drugs was inefficiency. The most frequent adverse effects were hypercholesterolemia in both groups and infections in BAR, with a high frequency of herpes zoster. No cardiovascular or thromboembolic events were observed.Disclosure of Interests:Cristina Valero: None declared, Alberto Calvo Garcia: None declared, Noelia García Castañeda: None declared, Ana Ortiz: None declared, Irene Llorente Speakers bureau: Gebro, Janssen, Sanofi, Lilly., Blanca Varas: None declared, Santos Castañeda: None declared, Rosario Garcia de Vicuna Grant/research support from: BMS, Lilly, MSD, Novartis, Roche, Consultant of: Abbvie, Biogen, BMS, Celltrion, Gebro, Lilly, Mylan, Pfizer, Sandoz, Sanofi, Paid instructor for: Lilly, Speakers bureau: BMS, Lilly, Pfizer, Sandoz, Sanofi, Esther Ramirez: None declared

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

“…Persistence of treatment was reported in three studies, with a treatment time of 7.6 months (mean) (43), 8.9 months (SD: 5.1 months) (47), 13.2 months (median) (46), respectively. One study also compared the persistence between patients receiving tofacitinib in monotherapy (9/23, 39.1%) versus in combination with csDMARD (26/43, 60.5%) (49).…”

“…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).…”

“…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).…”

“…The number of RA patients included in each series that were treated with tofacitinib varied, ranging from 4/81 (4.9%) (44) and reaching 81/81 patients (100%) in series that only included RA patients with tofacitinib (45). The mean age of patients analyzed ranged between 43.7 years (standard deviation, SD: 12.2 years) (53) and 61.2 years (SD: 13.2 years) (43), while the median age varied from 61.0 years (range: 40.0-74.0) (41) to 62.9 years (range: 49.9-74.4 years) (46). According to RA prevalence, a higher percentage of women received tofacitinib (between 58.0% [16/28 of patients] (38) and 94.4% [17/18]) (41) Disease activity at baseline was evaluated in nine studies with the Disease Activity Score 28 (DAS28), showing that patients who received JAK inhibitors had initially a moderate disease activity (defined as DAS28 score range: 3.2-5.1; DAS28: 4.3 (48), DAS28: 4.5, SD: 1.5 (40), DAS28/ C-reactive protein [CPR]: 4.5, range: 1.6-6.4, DAS28: 4.8, SD: 0.9 (47), DAS28: 4.8 (38), DAS28: 4.9, SD: 0.9 (39), and DAS28: 4.9, SD: 1.1 ( 51)); or high disease activity (DAS28: 5.2, range: 4.3-6.3; DAS28 score > 5.1, DAS28-CPR: 5.4, SD: 0.91 (43), DAS28-erythrocyte sedimentation rate [ESR]: 6.1, range: 3.8-5.3 ( 42)).…”

“…Similarly, another study reported a baseline median DAS28 of 6.1 (range: 3.8-5.3) and a final median DAS28 of 5.5 (range: 2.6-3.6) in a sample of 9 patients (42). Only one study reported a higher reduction in the DAS28, with a baseline median of 4.8 (range: 3.3-6.2) and a final median DAS28 of 2.61 (range: 2.5-3.7) (46).…”