FRI0117 INCIDENCE RATE OF HERPES ZOSTER IN RHEUMATOID ARTHRITIS PATIENTS UNDER TOFACITINIB: REAL-LIFE DATA FROM TURKEY – HURBIO REGISTRY

Background:Tofacitinib (TOF) is an orally administered Janus Kinase (JAK) inhibitor and is commonly used in rheumatoid arthritis. There is a heterogeneity among numbers reported from different continents about herpes zoster (HZ) incidence rate (1-3). However, data about HZ risk in our country, which stands like a bridge between Asia and Europe, is lacking.Objectives:To assess the real-life incidence of herpes zoster in RA patients under tofacitinib.Methods:We analyzed all patients who had at least 1 control visit under tofacitinib and registered to HURBIO database. We calculated incidence rate by dividing the number of patients with herpes zoster to total follow-up years, then multiplied by 100 (per 100 patient-years).Results:A total of 204 (174 (85.4%) female) patients were recruited. Mean age was 53.2±12.5 years. Mean disease duration was 11.5±8.1 years. Rheumatoid factor and anti-CCP antibodies were positive in 135/198 (68.1 %) and 115/171 (67.2 %) patients, respectively. Median follow-up while receiving TOF was 11.6 (IQR:5.2-26.2) months. Combination with DMARDs was used in 83.3% of patients. 55.5% of patients was biologic-naive. Eleven (5.3%, incidence rate: 3.9 (2.3-8.5; % 95 CI) per 100 patient-years) patients had zona zoster. Ten of these patients was female, median age was 59 (IQR; 52-69) and 4 of them was older than 65 years-old. Rheumatoid factor was positive in 9 patients. Only 1 of these patients had diabetes. Median follow-up of these patients under TOF was 8.1(IQR: 6-25) months. Ten of these patients had concomitant DMARDs (9 hydroxycholoroquine, 4 methotrexate, 2 leflunomide; according to last follow-up visit) and 9 of them received concomitant steroids (med(IQR); 4 (1-8) mg- at equivalant methyl-prednisolon dose). Eight of them was biologic-naive. Tofacitinib was discontinued in 4 of these patients.Conclusion:In this real-life data from Turkey, we found a HZ incidence rate similar to that reported from USA and global data; however, we found a lower incidence rate that reported from Japan (Figure 1).Figure 1.Reported herpes zoster incidence rates across different countries (numbers in paranthesis indicate reference number)References:[1]Winthrop KL, Curtis JR, Lindsey S, Tanaka Y, Yamaoka K, Valdez H, et al. Herpes Zoster and Tofacitinib: Clinical Outcomes and the Risk of Concomitant Therapy. Arthritis & rheumatology (Hoboken, NJ). 2017;69(10):1960-8.[2]Curtis JR, Xie F, Yun H, Bernatsky S, Winthrop KL. Real-world comparative risks of herpes virus infections in tofacitinib and biologic-treated patients with rheumatoid arthritis. Ann Rheum Dis. 2016;75(10):1843-7.[3]Yamanaka H, Tanaka Y, Takeuchi T, Sugiyama N, Yuasa H, Toyoizumi S, et al. Tofacitinib, an oral Janus kinase inhibitor, as monotherapy or with background methotrexate, in Japanese patients with rheumatoid arthritis: an open-label, long-term extension study. Arthritis Res Ther. 2016;18:34.Disclosure of Interests:Emre Bilgin: None declared, Furkan Ceylan: None declared, Emine Duran: None declared, Ertugrul Cagri Bolek: None declared, Bayram Farisoğullari: None declared, Gözde Kübra Yardimci: None declared, Levent Kiliç: None declared, Ali Akdoğan: None declared, Omer Karadag: None declared, Şule Apraş Bilgen: None declared, Sedat Kiraz: None declared, Ali İhsan Ertenli: None declared, Umut Kalyoncu Consultant of: Abbvie, Amgen, Janssen, Lilly, Novartis, UCB

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Serious infections in ANCA-associated vasculitides in the biologic era: real-life data from a multicenter cohort of 162 patients

Arthritis Research & Therapy ◽

10.1186/s13075-021-02452-8 ◽

2021 ◽

Vol 23 (1) ◽

Author(s):

Konstantinos Thomas ◽

Evangelia Argyriou ◽

Noemin Kapsala ◽

Alexandros Panagiotopoulos ◽

Aglaia Chalkia ◽

...

Keyword(s):

Incidence Rate ◽

Granulomatosis With Polyangiitis ◽

Strong Predictor ◽

Real Life ◽

Maintenance Phase ◽

Life Study ◽

Life Data ◽

Real Life Data ◽

Serious Infections

Abstract Background Serious infections (SI) are common in patients with ANCA-associated vasculitides (AAV) like granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA). Real-life data regarding their incidence and predisposing factors—after the introduction of B cell depleting agents—are limited while data quantifying the risk per treatment modality and year of the disease are missing. Here, we aim to describe in details the incidence and the risk factors for SI in a contemporary AAV cohort. Methods Multicenter, observational, retrospective study of AAV patients followed in three tertiary referral centers. Results We included 162 patients with GPA (63%) and MPA (37%), males 51.9%, mean age 60.9 years, ΑΝCA+ 86%, and generalized disease 80%. During follow-up (891.2 patient-years, mean 5.4 years), 67 SI were recorded in 50 patients at an incidence rate of 7.5 per 100 patient-years. The SI incidence rate was higher during induction with cyclophosphamide (CYC) compared to rituximab (RTX, 19.3 vs. 11.3 per 100 patient-years, respectively) while it was lower and comparable between RTX and other regimens (5.52 vs. 4.54 per 100 patient-years, respectively) in the maintenance phase. By multivariate analysis, plasmapheresis (PLEX) and/or dialysis was a strong predictor for an SI during the 1st year after diagnosis (OR = 3.16, 95% CI 1.001–9.96) and throughout the follow-up period (OR = 5.21, 95% CI 1.93–14.07). In contrast, a higher baseline BVAS (OR = 1.11, 95% CI 1.01–1.21) was associated with SI only during the 1st year. Conclusions In this real-life study of patients with AAV, the SI incidence was higher during CYC compared to RTX induction while there was no difference between RTX and other agents used for maintenance therapy. Higher disease activity at baseline and need for PLEX and/or dialysis were independent factors associated with an SI.

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Impact of the combined presence of erosions and ACPA on rheumatoid arthritis disease activity over time: results from the METEOR registry

RMD Open ◽

10.1136/rmdopen-2019-000969 ◽

2019 ◽

Vol 5 (2) ◽

pp. e000969

Author(s):

Sytske Anne Bergstra ◽

Maura C Couto ◽

Nimmisha Govind ◽

Arvind Chopra ◽

Karen Salomon Escoto ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Disease Activity ◽

Cox Regression ◽

Reference Group ◽

Real Life ◽

Similar Response ◽

Life Data ◽

Real Life Data ◽

Over Time

ObjectiveTo investigate associations between baseline presence of erosions and/or anti-citrullinated protein antibodies (ACPA) on functional ability, disease activity and treatment survival over time.MethodsReal life data from newly diagnosed rheumatoid arthritis patients were identified in the international METEOR registry. Patients were grouped according to presence/absence of ACPA and/or erosions at baseline. Associations between the presence of ACPA and/or erosions (four groups) with the change of Disease Activity Score (DAS) and Health Assessment Questionnaire (HAQ) over time were assessed using linear mixed models during maximum 6 or maximum 12 months from baseline. Treatment survival was assessed using multiple failure-times Cox regression.ResultsData were included from 701 ACPA‒/erosions‒, 334 ACPA‒/erosions+, 1585 ACPA+/erosions‒ and 1993 ACPA+/erosions+ patients. We found statistically significant differences in DAS and HAQ change over time between the four groups, both after maximum follow-up durations of 6 and of 12 months, but after stratification differences proved small and not clinically meaningful. Patients in the ACPA‒/erosions‒ group were less likely to switch treatment compared with the ACPA+/erosions‒ reference group (p<0.001). The other two ACPA/erosions groups did not differ from the reference group.ConclusionsIn this analysis of worldwide real life data, we found statistically significant, but clinically irrelevant differences in treatment response to initial disease modifying anti-rheumatic drug therapies as measured by DAS and HAQ in ACPA‒/erosions‒, ACPA‒/erosions+, ACPA+/erosions‒ and ACPA+/erosions+ rheumatoid arthritis patients. However, after maximum follow-up durations of 6 and 12 months all groups had a similar response to initial treatment, but with a lower likelihood to switch treatment for ACPA‒/erosions‒ patients during the first year of follow-up.

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Congestive heart failure: Change in risk factors, comorbidity and age at the time of first hospitalization. Follow-up of a population cohort between 2011 and 2016 using real life data

Revue d Épidémiologie et de Santé Publique ◽

10.1016/j.respe.2018.05.202 ◽

2018 ◽

Vol 66 ◽

pp. S314

Author(s):

F. Aizpuru ◽

E. Millan ◽

I. Garmendia ◽

M. Mateos ◽

J. Librero

Keyword(s):

Risk Factors ◽

Heart Failure ◽

Congestive Heart Failure ◽

Real Life ◽

Life Data ◽

Population Cohort ◽

Real Life Data

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P663 Efficacy of tofacitinib in patients with ulcerative colitis after previous ineffective biological therapies

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjz203.791 ◽

2020 ◽

Vol 14 (Supplement_1) ◽

pp. S545-S546

Author(s):

M Rutka ◽

K Farkas ◽

D Pigniczki ◽

K Szántó ◽

B Anita ◽

...

Keyword(s):

Ulcerative Colitis ◽

Clinical Response ◽

Induction Therapy ◽

Dose Escalation ◽

Real Life ◽

Janus Kinase ◽

Inadequate Response ◽

Mayo Score ◽

Number Of Patients

Abstract Background Tofacitinib (TFC) is an oral, small-molecule Janus kinase inhibitor, which was recently approved for moderate to severe ulcerative colitis (UC). The aim of the current real-life study was to determine efficacy of TFC induction therapy regarding the clinical response and remission in patients with active UC. We evaluated short-term efficacy data in a Hungarian cohort with prior exposure to other biological agents such as anti-TNF drugs and vedolizumab. Methods In this single-centre retrospective study, patients with TFC introduction were included. Since January 2019, a total of 16 patients received an oral TFC induction therapy in a dose of 10 mg twice daily for 8 weeks. Endoscopic activity was evaluated by endoscopic Mayo (eMayo) score before the introduction of TFC and in case of an inadequate therapeutic response to the 5-mg-therapy to confirm therapeutic decision-making. Based on the evaluation of clinical symptoms and laboratory parameters, we either kept the dosage or reduced the dose to 5 mg according to local regulations. We also collected data from the 16. and 24. weeks of the therapy. Primary endpoints were a clinical response (as a reduction in partial Mayo Score [pMayo] by minimum 3 points) or remission (as a Mayo score of the maximum of 2 points and without blood in stool) at week 8. Results Sixteen patients had received the induction therapy (mean age: 36 years, 7 males and 9 females) in our centre. After 8 weeks, 12 (75%) patients responded to the TFC induction therapy and 6 (37.5%) of them were in remission. Four patients were primary non-responders (25%). Corticosteroid therapy (18 ± 7 mg) was required during the induction in 4 responder cases, which could be stepped down by week 8. As a continuous maintenance therapy, 4 patients have already reached the 16th week and 8 have completed the 24th week. By the end of the follow-up, 12 patients responded and 10 was in remission. During the observation period, 3 patients had to remain on 10 mg TFC dose, 6 patients required dose escalation from 5 mg to 10 mg and 5 mg was sufficient in case of only 3 patients after the introduction. Endoscopic activity showed a moderate decrease from 2.5 ± 0.5 eMayo score to 2 ± 1 (n = 7) until week 16. In respect the responder patients, CRP levels decreased from the mean of 7.23 to 5.02. No serious side-effects were observed during the follow-up. Conclusion After the 8-week TFC induction therapy, the response rate was high and only every fourth patients were non-responder. A low number of patients had adequate reactions to the 5 mg-therapy after the introduction, but TFC is effective with dose-escalation in respect of clinical response and remission in patients with UC, who have had an inadequate response to previous biological therapy.

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Effects of Anti-TNF Alpha Drugs on Disability in Patients with Rheumatoid Arthritis: Long-Term Real-Life Data from the Lorhen Registry

BioMed Research International ◽

10.1155/2014/416892 ◽

2014 ◽

Vol 2014 ◽

pp. 1-8 ◽

Cited By ~ 5

Author(s):

Matteo Filippini ◽

Chiara Bazzani ◽

Fabiola Atzeni ◽

Piercarlo Sarzi Puttini ◽

Antonio Marchesoni ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Marked Improvement ◽

Real Life ◽

Tnf Alpha ◽

First Year ◽

Life Data ◽

Highly Active ◽

Real Life Data ◽

History Of

This study involving 1033 patients with RA confirms the effectiveness of etanercept, adalimumab, and infliximab in reducing RA-related disability even in patients with a history of highly active and longstanding RA. Moreover, we found that the improvement in disability was biphasic, with a marked improvement during the first year of anti-TNF therapy, followed by slower but significant recovery over the subsequent four years.

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Epidemiology and patterns of care of intrahepatic cholangiocarcinoma (iCCA) in France: Real-life data from the French National Hospital‐Discharge Summaries Database System (PMSI).

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e16624 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e16624-e16624

Author(s):

Cindy Neuzillet ◽

Corinne Emery ◽

Clément Teissier ◽

Stéphane Bouée ◽

Astrid Lièvre

Keyword(s):

Intrahepatic Bile Duct ◽

Real Life ◽

High Volume ◽

Cancer Registries ◽

Best Supportive Care ◽

Patterns Of Care ◽

University Hospitals ◽

Life Data ◽

Real Life Data

e16624 Background: Little is known about epidemiology and patterns of care of iCCA in daily clinical practice. The aims of this study were to estimate from real-life data the incidence of iCCA in France and to describe the healthcare pathways of these patients (pts). Methods: A retrospective analysis was carried out using the nationwide prospective French PMSI database. All pts with a new diagnosis of "carcinoma of the intrahepatic bile duct" who had a 1st hospital stay in Medicine, Surgery and Obstetrics departments (MSO) between 2014 and 2015 with a 2-year follow-up were included. Data related to the 1st identified stay (S1) in MSO and on all subsequent stays in MSO, Aftercare and Rehabilitation (SSR) or Home Hospitalizations (HAD) were analyzed. Results: A total of 3,650 new iCCA cases were identified. At S1 (admission via emergency room [ER] in 28%), median age of pts was 73y, 57% were male and 35% had metastases. Jaundice/anemia/ascites/cholangitis were reported in 17%/16%/12%/7%, respectively. Pts care at S1 was mainly provided in general hospitals (CHG, 60%), rather than university hospitals (CHU, 15%), private (20%) or cancer centers (CLCC, 6%). 896 (24%) pts died during S1: they were more frequently hospitalized via ER (48% vs 23%), metastatic (52% vs 35%) and symptomatic. Subsequent stays were identified for 2,507 pts (69%). Similarly to S1, most pts were managed in CHG during their follow-up (70% vs 20% in CHU and 12% in CLCC). Based on the number of pts treated over the study period, centers were classified as low (≤5 pts, 68%), intermediate (5-20 pts, 26%) and high volume ( > 20 pts, 6%). 47% of the high-volume centers were CHU/CLCC. Three healthcare pathways were defined: surgery (n = 519; 14%), chemotherapy (CT) without surgery (n = 812; 22%) and best supportive care (BSC) (n = 2,319; 63%). CT, surgery and BSC were most frequently performed in CLCC, CHU and CHG, respectively. Pts who received CT (mean time between S1 and start of CT: 1.9 months) were younger, less frequently hospitalized via ER and less symptomatic at S1. A palliative care code was associated with S1 in 25% of pts and with a subsequent MSO/SSR/HAD stay in 60%. Conclusions: This real-life, medico-administrative study, covering all hospitalized patients in France, reveals a higher incidence of iCCA than that previously reported by cancer registries. It also highlights the severity of this disease, the central role of CHG in the management of pts and the expertise of CHU and CLCC for surgery and CT, respectively.

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Effectiveness, Tolerability, and Safety of Tofacitinib in Rheumatoid Arthritis: A Retrospective Analysis of Real-World Data from the St. Gallen and Aarau Cohorts

Journal of Clinical Medicine ◽

10.3390/jcm8101548 ◽

2019 ◽

Vol 8 (10) ◽

pp. 1548 ◽

Cited By ~ 12

Author(s):

Mueller ◽

Hasler ◽

Popp ◽

Mattow ◽

Durmisi ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Disease Activity ◽

Randomized Clinical Trials ◽

Liver Enzymes ◽

Real Life ◽

Gastrointestinal Symptoms ◽

Janus Kinase ◽

Secondary Outcome ◽

Low Disease Activity

: Introduction: Tofacitinib is an oral JAK inhibitor indicated for the treatment of rheumatoid arthritis (RA). The efficacy and safety of tofacitinib have been shown in several randomized clinical trials. The study presented here aimed to assess the clinical tolerability and effectiveness of tofacitinib among RA patients in real life. Methods: Consecutive patients between January 2015 and April 2017 with RA who fulfilled the American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) 2010 criteria were included in a prospectively designed analysis of retrospective data. Patients were initiated on tofacitinib 5 mg bid. The primary objective was to analyze the safety of tofacitinib in a real-life cohort. Safety was assessed by the reasons to stop tofacitinib during follow up and changes of liver enzymes, hemoglobin, and creatinine. The secondary outcome was to analyze the frequency of and time to achieve low disease activity (LDA) and remission as defined by 28 joint count disease activity score (DAS28). Results: A total of 144 patients were treated with tofacitinib. A total of 84.9% of patients were pre-exposed to at least one biological agent. The average DAS28 at the initiation of tofacitinib was 4.43. A total of 50.0% of patients were positive for rheumatoid factor and 49.0% for ACPA. The mean follow up was 1.22 years (range 10d–3.7a) after initiation of tofacitinib treatment. A total of 94 (64.4%) patients remained on tofacitinib during follow-up. The average time to stop tofacitinib was 190.0 days. Reasons to stop tofacitinib were: insufficient response (n = 23), gastrointestinal symptoms (n = 18), infection (n = 5), myalgia (n = 2), remission (n = 2), headache (n = 2), cough, blue finger syndrome, intolerance, heartburn, psoriasis, and increased liver enzymes (all n = 1). Increased alanine amino transferase (ALAT) or aspartate amino transferase (ASAT) > 2× upper limit of normal (ULN) were detected in 3.3% and 4.4% of patients, respectively. Hemoglobin decrease of >10% was detected in 15.1% of the patients and decreased lymphocytes <500/μL in 3.4%. An increase of creatinine >20% was detected in 9.4% of patients. A total of 62.9% and 50.0% of the patients achieved low disease activity (LDA) or remission after a median of 319 and 645 days, respectively. These rates were significantly higher in patients naïve to biologic agents as compared to patients pre-exposed to biologics (LDA: naïve 100% 92 d, pre-exposed 57.0% 434 d, p ≤ 0.001; remission: naïve 86.7% 132 d, pre-exposed 44.1%, 692 d, p = 0.001). Conclusions: Tofacitinib is a safe and effective treatment option for patients with RA. Tofacitinib may induce high rates of LDA and remission in patients with active disease, even after the use of one or more biologics, though the rate appeared higher in patients naïve to biologics. Tofacitinib may be a valuable option in a treat-to-target approach. Our data demonstrate that Janus kinase (JAK) inhibitors are safe and efficacious in real life patients.

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