scholarly journals Serious infections in patients with self-reported psoriatic arthritis from the Psoriasis Longitudinal Assessment and Registry (PSOLAR) treated with biologics

2019 ◽  
Vol 3 (1) ◽  
Author(s):  
Christopher T. Ritchlin ◽  
Mona Stahle ◽  
Yves Poulin ◽  
Jerry Bagel ◽  
Soumya D. Chakravarty ◽  
...  

Abstract Background Patients with psoriatic arthritis (PsA) have increased risk of adverse events, including serious infections (SI), compared with psoriasis patients. Methods Patients eligible for, or receiving conventional systemic and biologic agents for psoriasis were followed prospectively using PSOLAR. Cohorts included: ustekinumab, tumor necrosis factor (TNF) inhibitors; infliximab; etanercept; adalimumab; non-biologic/methotrexate (MTX) (reference group); and non-biologic/non-MTX. Multivariate analyses using Cox hazard regression were used to identify factors associated with time to first SI. Rates of SI in PSOLAR psoriasis patients with self-reported PsA and possible risks with biologic therapy were evaluated. Results PSOLAR enrolled 4315 psoriasis patients with self-reported PsA. The overall population (N = 2401) included patients (n): 628 ustekinumab; 1413 TNF inhibitors; 258 infliximab; 481 etanercept; 674 adalimumab; 54 other biologics, 98 non-biologic/MTX; 208 non-biologic/non-MTX. Overall, 138 SI were reported with incidence rates per 100 patient-years as follows: a) ustekinumab: 1.00; b) TNF inhibitors: 2.22; c) infliximab: 2.12; d) etanercept: 2.58; e) adalimumab: 1.99; f) non-biologic/MTX: 3.01; g) and non-biologic/non-MTX: 2.31. Age, time-dependent disease activity Physician’s Global Assessment (PGA) of 4, 5, history of infection, and diabetes were associated with increased risk for SI (p < 0.05) in self-reported PsA patients. Biologic groups, other than ustekinumab, had numerically higher rates of SI. Conclusions PSOLAR psoriasis patients with self-reported PsA in the TNF inhibitors, infliximab, adalimumab, etanercept, and MTX cohorts had numerically higher SI rates than the ustekinumab cohort, although not statistically significant. Age, PGA 4, 5, history of infection, and diabetes were associated with an increased risk for SI, irrespective of biologic exposure. Trial registration NCT00508547; Registered July 30, 2007.

2016 ◽  
Vol 76 (2) ◽  
pp. 386-391 ◽  
Author(s):  
Louise K Mercer ◽  
Johan Askling ◽  
Pauline Raaschou ◽  
William G Dixon ◽  
Lene Dreyer ◽  
...  

ObjectivesSome studies have reported a possible association between exposure to tumour necrosis factor (TNF) inhibitors and an increased risk of melanoma. The aim of this study was to investigate the incidence of invasive cutaneous melanomas in patients with rheumatoid arthritis (RA) treated with TNF inhibitors (TNFi), other biologic disease modifying drugs and non-biologic therapy.MethodsEleven biologic registers from nine European countries participated in this collaborative project. According to predefined exposure definitions, cohorts of patients with RA were selected. Using the country-specific general population of each register as reference, age, sex and calendar year standardised incidence ratios (SIRs) of invasive histology-confirmed cutaneous melanoma were calculated within each register. Pooled SIR and incidence rate ratios (IRRs) comparing biologic cohorts to biologic-naïve were calculated across countries by taking the size of the register into account.ResultsOverall 130 315 RA patients with a mean age of 58 years contributing 579 983 person-years were available for the analysis and 287 developed a first melanoma. Pooled SIRs for biologic-naïve, TNFi and rituximab-exposed patients were 1.1 (95% CI 0.9 to 1.4), 1.2 (0.99 to 1.6) and 1.3 (0.6 to 2.6), respectively. Incidence rates in tocilizumab and abatacept-exposed patients were also not significantly increased. IRR versus biologic-naïve patients were: TNFi 1.1 (95% CI 0.8 to 1.6); rituximab 1.2 (0.5 to 2.9).ConclusionsThis large European collaborative project did not confirm an overall increased risk of melanoma following exposure to TNFi.


2021 ◽  
pp. annrheumdis-2021-221007
Author(s):  
Ingrid Egeland Christensen ◽  
Siri Lillegraven ◽  
Pawel Mielnik ◽  
Gunnstein Bakland ◽  
Liz Loli ◽  
...  

ObjectivesTo estimate the incidence of serious infections (SIs) in patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA) treated with tumour necrosis factor inhibitor (TNFi), and compare risk of SIs between patients with RA and PsA.MethodsWe included patients with RA and PsA from the NORwegian-Disease Modifying Anti-Rheumatic Drug registry starting TNFi treatment. Crude incidence rates (IRs) and IR ratio for SIs were calculated. The risk of SIs in patients with RA and PsA was compared using adjusted Cox-regression models.ResultsA total of 3169 TNFi treatment courses (RA/PsA: 1778/1391) were identified in 2359 patients. Patients with RA were significantly older with more extensive use of co-medication. The crude IRs for SIs were 4.17 (95% CI 3.52 to 4.95) in patients with RA and 2.16 (95% CI 1.66 to 2.81) in patients with PsA. Compared with the patients with RA, patients with PsA had a lower risk of SIs (HR 0.59, 95% CI 0.41 to 0.85, p=0.004) in complete set analysis. The reduced risk in PsA versus RA remained significant after multiple adjustments and consistent across strata based on age, gender and disease status.ConclusionsCompared with patients with RA, the risk of SIs was significantly lower in patients with PsA during TNFi exposure.


2019 ◽  
Vol 79 (2) ◽  
pp. 285-291 ◽  
Author(s):  
Xintong Li ◽  
Kathleen M Andersen ◽  
Hsien-Yen Chang ◽  
Jeffrey R Curtis ◽  
G Caleb Alexander

ObjectiveTo examine whether initiation of interleukin (IL)-17, IL-12/23 or tumour necrosis factor (TNF) inhibitor is associated with an increased risk of serious infection among real-world psoriasis (PsO) or psoriatic arthritis (PsA) patients.MethodsWe assembled a retrospective cohort of commercially insured adults in the USA diagnosed with PsO or PsA between 2015 and 2018. Exposure was dispensation for IL-17 (ixekizumab or secukinumab), IL-12/23 (ustekinumab) or TNF (adalimumab, certolizumab pegol, etanercept, golimumab and infliximab). The outcome was infection requiring hospitalisation after biologic initiation. Incidence rates (IRs) per 100 person-years were computed, and hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated using Cox proportional hazards regression models, adjusted for inverse probability of treatment-weighted propensity scores.ResultsA total of 11 560 new treatment episodes were included. Overall, 190 serious infections (2% of treatment episodes) were identified in 9264 person-years of follow-up. Class-specific IRs were similar among IL-17 and TNF, yet significantly lower for IL-12/23. After adjustment for propensity scores, there was no increased risk with IL-17 compared with either TNF (HR=0.89, 95% CI 0.48 to 1.66) or IL-12/23 (HR=1.12, 95% CI 0.62 to 2.03). By contrast, IL-23/23 were associated with a lower risk of infections than TNF (HR=0.59, 95% CI 0.39 to 0.90).ConclusionsRelative to TNF and IL-17, IL-12/23 inhibitors were associated with a reduced risk of serious infection in biologic-naïve patients with PsO or PsA. In biologic-experienced individuals, there was no difference in infection risk across TNF, IL-17 or IL-12/23 inhibitors.


Rheumatology ◽  
2020 ◽  
Vol 59 (Supplement_2) ◽  
Author(s):  
Mariam Malik ◽  
Himashi Anver ◽  
Ernest Wong

Abstract Background Toxoplasma gondii is thought to infect up to a third of world’s population. Incidence rate of 0.4/100,000 has been calculated in Britain, culminating in a life-time risk of 18/100,000. Cats are primary hosts, but humans and warm-blooded animals can be infected by consumption of contaminated food/water. Although in most patients, it’s self-limiting, it can be devastating in immunosuppressed patients and may cause eye manifestations, cerebral abscesses or disseminated infection. Immunosuppressive therapies including treatment with biologics increases the risk and may also cause toxoplasmosis reactivation. Methods This is case of 57 year old lady with psoriatic arthritis. She has past history of congenital vision impairment in the left eye and is HLA B27 negative. She enjoyed horse-riding and had a pet dog. Initially she was started on methotrexate. Sulfasalazine was added later. Due to ongoing active disease, etanercept was used for 6 months, before being switched to cetrolizumab due to ineffectiveness. She had this for 5 months and then switched to infliximab, 3mg/kg, 8 weekly. In May 2019, she was seen by Ophthalmology for 2 weeks history of blurred vision and floaters in right eye. She was diagnosed to have panuveitis and had positive IgM for toxoplasma. Bloods revealed negative TB screen, HIV, Hep B&C, syphilis, lyme and anti-streptolysin antibody tests were negative. Infliximab levels were sub-therapeutic. She was commenced on 30mg prednisolone for possible inflammatory process secondary to seronegative arthropathy, but acute toxoplasmosis could not be excluded. Hence, she was started on azithromycin and had vitreous biopsy. Toxoplasma was detected in the sample, confirming acute infection. Methotrexate and infliximab were stopped. MRI head ruled out intracranial involvement. Following treatment of acute toxoplasmosis, adalimumab is now being considered for management of her inflammatory disease, with close monitoring by local infectious-disease team and specialist ophthalmology unit. Results This lady developed ocular toxoplasmosis and panuveitis, whilst on immunosuppression for psoriatic arthritis. She was a horse-rider and had exposure to dogs. Diagnosing toxoplasma in immunocompromised can be difficult. Isolation of T. gondii in tissue usually confirms diagnosis. Some forms of immunosuppressive treatment may be associated with increased risk of reactivation of toxoplasmosis but there is not much evidence to assess the relative risk of various therapies. Conclusion Ocular toxoplasmosis needs to be considered in patients receiving immunosupression and presenting with inflammatory eye symptoms. Management requires specialist input and close monitoring. Further research into diagnostic techniques, possibility of using prophylaxis in high-risk patients and management guidelines would be helpful. Disclosures M. Malik None. H. Anver None. E. Wong None.


Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3463-3463
Author(s):  
Micah Denay McCumber ◽  
Aaron Mark Wendelboe ◽  
Janis Campbell ◽  
Kai Ding ◽  
Michele G Beckman ◽  
...  

Background: Patients with cancer are at elevated risk for venous thromboembolism (VTE). Active cancer contributes a 4-7 fold increased risk for VTE; however, the incidence of VTE stratified by subpopulations of patients diagnosed with cancer, especially race/ethnicity, is uncertain. Objective: Describe the incidence of VTE among adult patients (age ≥ 18 years) with a cancer diagnosis in Oklahoma County, OK according to age, gender, race, and cancer type. Methods: In collaboration with the Centers for Disease Control and Prevention, we established a population-based surveillance system for VTE in Oklahoma County, OK between April 1, 2012-March 31, 2014 to estimate the incidences of first-time and recurrent VTE events. The Commissioner of Health made VTE a reportable condition and delegated surveillance-related responsibilities to the University of Oklahoma, College of Public Health. Active surveillance involved reviewing imaging studies (e.g., chest computed tomography and compression ultrasounds of the extremities) from all inpatient and outpatient facilities in the county and collecting demographic, treatment and risk factor data on all VTE case-patients. Patients were linked to the Oklahoma Central Cancer Registry. Any patient with a cancer diagnosis since 1997, excluding basal or squamous cell carcinoma, were included in the population-at-risk. Active cancer was defined as metastatic or a diagnosis ≤6 months before their VTE diagnosis. Poisson regression was used to estimate incidence rates (IRs) and 95% confidence intervals (CIs), which are reported per 1,000 person years (PY). Estimates with &lt;10 events were suppressed. Results: Among all patients aged ≥18 years with a cancer diagnosis since 1997, 1.5% (n = 881) had a VTE event during the 2-year surveillance period. The overall annual age-adjusted incidence of VTE among those with cancer was 6.8 per 1,000 PY (95% CI: 5.81, 7.95). The demographic-specific incidence rates are summarized in Table 1. The VTE incidence did not significantly differ by sex. When stratified by age, annual VTE incidence was similar among those aged 18-39 years (6.1/1,000 PY, 95% CI: 4.35, 8.61), 40-59 years (6.2/1,000 PY, 95% CI: 5.4, 7.14), and 60-79 years (7.2/1,000 PY, 95% CI: 6.55, 7.90), however, the incidence was significantly higher (p&lt;0.05) in those aged 80+ years (10.1/1,000 PY, 95% CI: 8.77, 11.61). When patients with a cancer diagnosis were stratified by race/ethnicity, non-Hispanic blacks had the highest VTE incidence (11.7/1,000 PY, 95% CI: 10.00, 13.59), followed by Hispanics (8.0/1,000 PY, 95% CI: 5.66, 11.44), non-Hispanic whites (6.9/1,000 PY, 95% CI: 6.41, 7.48), other non-Hispanic/unknown (5.8/1,000 PY, 95% CI: 3.45, 9.85), and non-Hispanic Native Americans (2.6/1,000 PY, 95% CI: 1.39, 4.79). VTE incidence was highest among those with active cancer or a history of cancer within the past three years, after which it appeared to decrease. When stratified by primary cancer type, VTE incidence was highest among those with brain cancer (16.6/1,000 PY, 95% CI: 11.06, 25.04) and lowest among those with prostate cancer (5.2/1,000 PY, 95% CI: 4.20, 6.44). As shown in Table 2, when stratified by cancer type, the incidence of VTE was higher (non-overlapping CIs) among those with active cancer compared to those with a history of cancer &gt;6 months for several tumor types. Discussion: The incidence of VTE among those with cancer differs by race/ethnicity, with non-Hispanic blacks bearing the highest burden of disease. The risk of VTE persists and is particularly elevated up to three years after a cancer diagnosis. Disclosures Raskob: Eli Lilly: Consultancy; Pfizer: Consultancy, Honoraria; Portola: Consultancy; Novartis: Consultancy; BMS: Consultancy, Honoraria; Janssen R&D, LLC: Consultancy, Honoraria; Tetherex: Consultancy; Daiichi Sankyo: Consultancy, Honoraria; Anthos: Consultancy; Bayer Healthcare: Consultancy, Honoraria; Boehringer Ingelheim: Consultancy.


Rheumatology ◽  
2020 ◽  
Vol 59 (12) ◽  
pp. 3657-3665
Author(s):  
Yantao Xu ◽  
Yuting Li ◽  
Mengyuan Dong ◽  
Zi’ang Gao ◽  
Xiang Chen ◽  
...  

Abstract Objectives We sought to systematically investigate the effectiveness of secukinumab in psoriatic arthritis (PsA) patients who previously received TNFs inhibitor (TNFi) treatment and those who were TNFi naïve. Methods Databases (PubMed, EMBase and Cochrane library) and ClinicalTrials.gov were searched from inception to 22 May 2020 for randomized control trails and observational studies of secukinumab, with or without a history of previous anti-TNFi treatment, in PsA. Effectiveness data were extracted and combined using a random-effects meta-analysis. The ACR20 and ACR50 (20% and 50% improvement in American College of Rheumatology response criteria) responses were the endpoints. Results Six randomized controlled trials that reported the effectiveness of secukinumab by previous anti-TNFi treatment were included. Among patients exposed to a prior anti-TNFi treatment (n = 738), 33.7% (249/738) of patients achieved an ACR20 response. In contrast, in the anti-TNFi-naïve group (n = 1754), 49.8% (873/1754) of patients achieved an ACR20 response. Prior treatment with anti-TNFi was significantly associated with a poorer response to secukinumab compared with the anti-TNFi-naïve group with an effect size of 2.09 (95% CI: 1.69, 2.58). Conclusion Some patients benefit from switching from TNFi to secukinumab, but previous anti-TNFi treatment is associated with poorer effectiveness of secukinumab.


Rheumatology ◽  
2021 ◽  
Author(s):  
Karin Hellgren ◽  
Christine Ballegaard ◽  
Bénédicte Delcoigne ◽  
René Cordtz ◽  
Dan Nordström ◽  
...  

Abstract Objectives To investigate whether TNF inhibitors (TNFi) are associated with increased risk of solid cancer in patients with psoriatic arthritis (PsA). Methods From the Nordic clinical rheumatology registers (CRR) here: SRQ/ARTIS (Sweden), DANBIO (Denmark), NOR-DMARD (Norway), ROB-FIN (Finland) and ICEBIO (Iceland) we identified PsA patients who started a first TNFi 2001–2017 (n = 9655). We identified patients with PsA not treated with biologics from (i) the CRR (n = 14 809) and (ii) the national patient registers (PR, n = 31 350). By linkage to the national cancer registers, we collected information on incident solid cancer overall and for eight cancer types. We used Cox regression to estimate hazard ratio (HR) with 95% CI of cancer (per country and pooled) in TNFi-exposed vs biologics-naïve, adjusting for age, sex, calendar period, comorbidities and disease activity. We also assessed standardized incidence ratios (SIR) in TNFi-exposed PsA vs the general population (GP). Results We identified 296 solid cancers among the TNFi-exposed PsA patients (55 850 person-years); the pooled adjusted HR for solid cancer overall was 1.0 (0.9–1.2) for TNFi-exposed vs biologics-naïve PsA from the CRR, and 0.8 (0.7–1.0) vs biologics-naïve PsA from the PRs. There were no significantly increased risks for any of the cancer types under study. The pooled SIR of solid cancer overall in TNFi treated PsA vs GP was 1.0 (0.9–1.1). Conclusion In this large cohort study from five Nordic countries, we found no increased risk of solid cancer in TNFi-treated PsA patients, neither for solid cancer overall nor for eight common cancer types.


Gut ◽  
2019 ◽  
Vol 69 (5) ◽  
pp. 852-858 ◽  
Author(s):  
Julien Kirchgesner ◽  
Nynne Nyboe Andersen ◽  
Fabrice Carrat ◽  
Tine Jess ◽  
Laurent Beaugerie

ObjectivePatients with IBD are at increased risk of acute arterial events. Antitumour necrosis factor (TNF) agents and thiopurines may, via their anti-inflammatory properties, lower the risk of acute arterial events. The aim of this study was to assess the impact of thiopurines and anti-TNFs on the risk of acute arterial events in patients with IBD.DesignPatients aged 18 years or older and affiliated to the French national health insurance with a diagnosis of IBD were followed up from 1 April 2010 until 31 December 2014. The risks of acute arterial events (including ischaemic heart disease, cerebrovascular disease and peripheral artery disease) were compared between thiopurines and anti-TNFs exposed and unexposed patients with marginal structural Cox proportional hazard models adjusting for baseline and time-varying demographics, medications, traditional cardiovascular risk factors, comorbidities and IBD disease activity.ResultsAmong 177 827 patients with IBD (96 111 (54%) women, mean age at cohort entry 46.2 years (SD 16.3), 90 205 (50.7%) with Crohn’s disease (CD)), 4145 incident acute arterial events occurred (incidence rates: 5.4 per 1000 person-years). Compared with unexposed patients, exposure to anti-TNFs (HR 0.79, 95% CI 0.66 to 0.95), but not to thiopurines (HR 0.93, 95% CI 0.82 to 1.05), was associated with a decreased risk of acute arterial events. The magnitude in risk reduction was highest in men with CD exposed to anti-TNFs (HR 0.54, 95% CI 0.40 to 0.72).ConclusionExposure to anti-TNFs is associated with a decreased risk of acute arterial events in patients with IBD, particularly in men with CD.


2019 ◽  
Vol 11 (1) ◽  
Author(s):  
Min-Kyung Lee ◽  
Kyungdo Han ◽  
Hyuk-Sang Kwon

Abstract Background Metabolic syndrome is associated with an increased risk of diabetes. This study investigated the associations between the number of metabolic syndrome components and diabetes risk by age, sex and BMI. Methods Data for 19,475,643 participants ≥ 20 years old with no history of diabetes were obtained between 2009 and 2012 and were accessed using the South Korean National Health Insurance Service. Metabolic syndrome was defined according to the modified criteria of the National Cholesterol Education Program Adult Treatment Panel III. We assessed the risk of diabetes according to the number of metabolic syndrome components after stratifying the study participants into groups by age (20–39, 46–64, ≥ 65 years), sex, and BMI (below or above 25). Results During an average of 5.13 years of follow-up, the incidence rates of diabetes increased with the number of metabolic syndrome components. Age and BMI gradually increased with the number of metabolic syndrome components. The multivariable-adjusted hazard ratios (HRs) for incident diabetes were 1.401, 1.862, 2.47, 3.164 and 4.501 for participants with one through five components, respectively, compared with those without metabolic syndrome components. The risk of diabetes was 1.79-, 2.18-, and 3.05-times higher for participants ≥ 65 years; 2.57-, 3.45-, and 5.18-times higher for participants 40–64 years; and 2.55-, 3.89-, and 6.31-times higher for participants 20–39 years of age with three through five components, respectively, compared to those with no components. There was no difference in the risk of diabetes between men and women. The HRs were 5.63 for participants with a BMI ≥ 25 and 3.98 for those with a BMI < 25 among individuals with five components. Conclusions The risk of diabetes was more strongly associated with the number of metabolic syndrome components among younger adults. In addition, the risk of diabetes across the number of metabolic syndrome components was greater in participants with a BMI ≥ 25.


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