RESUMEN
OBJECTIVES: To assess the potential impact of targeted therapies for psoriatic arthritis (PsA) on symptomatic treatments (non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, opioid analgesics), methotrexate and mood disorder treatments and on hospitalisation and sick leave. METHODS: Using the French health insurance database, this nationwide cohort study included adults with PsA who were new users (not in the year before the index date) of targeted therapies for ≥9 months during 2015-2021. Main endpoints were difference in proportion of users of associated treatments, hospitalisations and sick leaves between 3 and 9 months after and 6 months before targeted therapy initiation. Logistic regression models adjusted for sex, age, psoriasis, inflammatory bowel disease and Charlson Comorbidity Index compared the impact of biologics initiation (tumour necrosis factor inhibitor (TNFi)/interleukin 17 inhibitor (IL17i)/IL12/23i) on associated treatment discontinuation. RESULTS: Among 9793 patients initiating targeted therapy for PsA (mean age: 51±13 years, 47% men), 62% initiated TNFi, 14% IL17i, 10% IL12/23i, 1% Janus kinase inhibitor, 12% phosphodiesterase-4 inhibitor. After treatment initiation, the proportion of treatment users was significantly reduced for NSAIDs (-15%), opioid analgesics (-9%), prednisone (-9%), methotrexate (-15%) and mood disorder treatments (-2%), along with decreased hospitalisations (-12%) and sick leaves (-4%). TNFi had a greater sparing effect on NSAIDs and prednisone use than IL17i (ORa=1.04, 95% CI=1.01 to 1.07; 1.04, 1.02 to 1.06) and IL12/23i (1.07, 1.04 to 1.10; 1.06, 1.04 to 1.09). Odds of methotrexate discontinuation was reduced with TNFi versus IL17i (0.96, 0.94 to 0.98) and IL12/23i (0.94, 0.92 to 0.97). CONCLUSIONS: Targeted therapy initiation for PsA reduced the use of associated treatment and healthcare, with TNFi having a slightly greater effect than IL17i and IL12/23i, except for methotrexate discontinuation.
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Artritis Psoriásica , Bases de Datos Factuales , Humanos , Masculino , Femenino , Artritis Psoriásica/tratamiento farmacológico , Persona de Mediana Edad , Adulto , Francia/epidemiología , Hospitalización/estadística & datos numéricos , Metotrexato/uso terapéutico , Estudios de Cohortes , Antiinflamatorios no Esteroideos/uso terapéutico , Terapia Molecular Dirigida , Anciano , Aceptación de la Atención de Salud/estadística & datos numéricos , Analgésicos Opioides/uso terapéutico , Seguro de Salud/estadística & datos numéricos , Ausencia por Enfermedad/estadística & datos numéricos , Corticoesteroides/uso terapéuticoRESUMEN
OBJECTIVE: To assess the risk of serious infection associated with different targeted therapies for psoriatic arthritis (PsA) in real-world settings. METHODS: This nationwide cohort study used the administrative healthcare database of the French health insurance scheme linked to the hospital discharge database to identify all adults with PsA who were new users of targeted therapies (adalimumab, etanercept, golimumab, certolizumab pegol, infliximab, secukinumab, ixekizumab, ustekinumab, and tofacitinib) from 1 January 2015 to 30 June 2021. The primary outcome was a serious infection (ie, requiring hospitalisation), in a time-to-event analysis using propensity score-weighted Cox models, with adalimumab as the comparator, estimating weighted HRs (wHRs) and their 95% CIs. RESULTS: A total of 12 071 patients were included (mean age 48.7±12.7 years; 6965 (57.7%) women). We identified 367 serious infections (3.0% of patients), with a crude incidence rate of 17.0 per 1000 person-years (95% CI, 15.2 to 18.7). After inverse propensity score weighting and adjustment for time-dependent covariates and calendar year, risk of serious infection was significantly lower for new users of etanercept (wHR 0.72; 95% CI, 0.53 to 0.97) or ustekinumab (wHR, 0.57; 95% CI, 0.35 to 0.93) than adalimumab new users. This risk was not statistically modified with the other targeted therapies. CONCLUSIONS: The incidence of serious infection was low for PsA patients who were new users of targeted therapies in real-world settings. Relative to adalimumab new users, this risk was lower among new users of etanercept and ustekinumab and unmodified for the other molecules.
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Artritis Psoriásica , Adulto , Humanos , Femenino , Persona de Mediana Edad , Masculino , Artritis Psoriásica/tratamiento farmacológico , Artritis Psoriásica/epidemiología , Adalimumab/efectos adversos , Etanercept , Ustekinumab , Estudios de Cohortes , Seguro de SaludRESUMEN
BACKGROUND: Rheumatoid arthritis (RA) can affect women of childbearing age. The management of patients with RA during pregnancy has evolved over the past decades, especially with the availability of new therapeutic molecules. OBJECTIVES: To describe pregnancy in women with RA, to compare pregnancy outcomes with those of women in the general population and to compare pregnancy outcomes in women with active and inactive RA. METHODS: Using the French National Health Data System, we identified all pregnancies ending between 2010 and 2020 in patients with and without RA. Characteristics were described. Active RA was defined by conventional synthetic/biological/targeted synthetic disease-modifying antirheumatic drug initiation, systemic or intra-articular corticosteroid administration and/or RA-related hospitalisation. Pregnancy outcomes were compared computing multivariable logistic marginal regression model using generalised estimating equation (GEE). RESULTS: We included 11 792 RA and 10 413 681 non-RA pregnancies. Among RA pregnancies, 74.5% ended in live births and 0.4% in stillbirths. RA pregnancies resulted more frequently in preterm births (adjusted OR (ORa) 1.84; 95% CI 1.69 to 2.00) and very preterm births (ORa 1.43; 95% CI 1.20 to 1.71), low birth weight (ORa 1.65; 95% CI: 1.52 to 1.90), caesarean section (ORa 1.46; 95% CI 1.38 to 1.55) and pregnancy-related hospitalisation (ORa 1.30; 95% CI 1.22 to 1.39). Disease activity decreased during pregnancy. Active RA had higher rates of prematurity (ORa 2.02; 95% CI 1.71 to 2.38), small for gestational age (ORa 1.53; 95% CI 1.28 to 1.83) and caesarean section (ORa 1.25; 95% CI 1.11 to 1.40) than non-active RA. CONCLUSION: Pregnancies in women with RA were associated with more adverse outcomes, especially if the disease was active. These findings should encourage physicians to closely monitor RA during this crucial period.
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Artritis Reumatoide , Complicaciones del Embarazo , Nacimiento Prematuro , Recién Nacido , Humanos , Embarazo , Femenino , Resultado del Embarazo/epidemiología , Nacimiento Prematuro/epidemiología , Cesárea , Artritis Reumatoide/complicaciones , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/epidemiología , Complicaciones del Embarazo/epidemiologíaRESUMEN
BACKGROUND: Sex differences in phenotype presentation, disease trajectory and treatment response in psoriatic arthritis (PsA) have been reported. Nevertheless, whether classes of targeted therapies differentially affect men and women with PsA remains unclear. OBJECTIVES: To assess the effect of sex on the long-term persistence of each class of targeted therapies in PsA. METHODS: This nationwide cohort study involved the administrative healthcare database of the French health insurance scheme linked to the hospital discharge database. We included all adults with PsA who were new users of targeted therapies (not in the year before the index date) during 2015-2021 and studied all treatment lines during the study period. Persistence was defined as the time from treatment initiation to discontinuation and was estimated by the Kaplan-Meier method. Comparison of persistence by sex involved multivariate frailty models with conventional synthetic disease-modifying antirheumatic drugs and prednisone as time-dependant variables. RESULTS: We included 14 778 patients with PsA who were new users of targeted therapies: 8475 (57%) women (mean age 50±13 years; 15 831 lines), 6303 (43%) men (mean age 51±13 years; 10 488 lines). Overall, 1-year persistence was 52% for women and 62% for men and at 3 years it was 27% and 39%, respectively. After adjustments, persistence was lower for women than men for inhibitors of tumour necrosis factor (TNFi) (adjusted HR (HRa) 1.4, 99% CI 1.3 to 1.5) and interleukin 17 inhibitor (IL17i) (HRa 1.2, 99% CI 1.1 to 1.3) but not IL12/23i (HRa 1.1, 99% CI 0.9 to 1.3), IL23i (HRa 1.1, 99% CI 0.7 to 1.5) or Janus kinase inhibitor (JAKi) (HRa 1.2, 99% CI 0.9 to 1.6). CONCLUSION: The treatment persistence was lower for women than men for TNFi and IL17i but not for IL12/23i, IL23i or JAKi.
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Antirreumáticos , Artritis Psoriásica , Adulto , Humanos , Femenino , Masculino , Persona de Mediana Edad , Artritis Psoriásica/tratamiento farmacológico , Artritis Psoriásica/epidemiología , Estudios de Cohortes , Antirreumáticos/uso terapéutico , Factor de Necrosis Tumoral alfa , Seguro de SaludAsunto(s)
Psoriasis , Humanos , Estudios Retrospectivos , Estudios de Cohortes , Comorbilidad , Psoriasis/epidemiologíaRESUMEN
OBJECTIVES: Rheumatoid arthritis (RA) is a chronic inflammatory disease mostly affecting the joints. Data on the prevalence of RA differ widely, depending on the study and country. Our objectives were to estimate the prevalence of RA in France and the mortality rate, characterise the causes of death, and identify prescribed treatments. METHODS: This nationwide cohort study was based on data of the French National Health Data System (SNDS) which covers 99% of the French population. All patients identified with RA based on specific ICD-10 codes (M05 and M06, except M06.1) between 2010 and 2019 were included. RESULTS: We identified 385,919 RA cases between 2010 and 2019, 318,243 of which were followed in 2019 (65.8±16.8 years, 72% women). The overall crude prevalence rate in 2019 was 0.47%: 0.66% for women and 0.28% for men. The crude annual mortality rate was 3.1%. The overall standardised mortality ratio (SMR) of RA patients relative to the French general population decreased over time, reaching 1.21 in 2019. Cause-specific mortality was increased in RA patients for cardiovascular (SMR 1.40, 95% confidence interval 1.36-1.43), respiratory system (1.80, 1.73-1.87), digestive system (1.73, 1.59-1.88), and urogenital system (1.73, 1.59-1.88) diseases and infections (1.91, 1.76-2.06). We found no excess mortality due to tumours. The prevalence of treatment with conventional synthetic and biological/targeted synthetic disease-modifying antirheumatic drugs for RA in 2019 was 41.9% (n=133,477) and 18.7% (n=59,409), respectively. CONCLUSION: Our results may provide a better understanding of RA and its care in France.
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Antirreumáticos , Artritis Reumatoide , Masculino , Humanos , Femenino , Estudios de Cohortes , Prevalencia , Causas de Muerte , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/epidemiología , Antirreumáticos/uso terapéuticoAsunto(s)
Espondiloartritis Axial , Sacroileítis , Espondiloartritis , Humanos , Articulación Sacroiliaca/diagnóstico por imagen , Articulación Sacroiliaca/patología , Radiografía , Imagen por Resonancia Magnética/métodos , Espondiloartritis/diagnóstico por imagen , Espondiloartritis/patología , Sacroileítis/diagnóstico por imagen , Sacroileítis/patologíaRESUMEN
OBJECTIVES: To assess the risk of major adverse cardiovascular events (MACEs) and venous thromboembolism events (VTEs) among patients initiating a Janus kinase inhibitor (JAKi) (tofacitinib and baricitinib) versus adalimumab in a large real-world population of patients with rheumatoid arthritis. METHODS: We conducted a nationwide population-based cohort study of the French national health data system, the exposed group initiating a JAKi and non-exposed group initiating adalimumab. We included all individuals who had their first dispensation of a JAKi or adalimumab between 1 July 2017 and 31 May 2021 and had rheumatoid arthritis. The primary endpoints were the occurrence of a MACE or VTE. Weighted hazard ratio (HRw) values were estimated with the inverse probability of treatment weighting method to account for confounding factors with concomitant administration of methotrexate as a time-varying variable. RESULTS: The cohort included 15 835 patients: 8481 and 7354 in the exposed and non-exposed groups (mean age 59.3 and 55.3 years, female 78.3% and 71.2%, respectively). During follow-up, 54 and 35 MACEs and 75 and 32 VTEs occurred in the exposed and non-exposed groups, respectively. Risk of MACEs for the exposed versus non-exposed group was not significant: HRw 1.0 (95% CI 0.7 to 1.5) (p=0.99), nor was risk of VTEs significant: HRw 1.1 (0.7 to 1.6) (p=0.63). Despite a lack of power, results were consistent among patients aged 65 years or older with at least one cardiovascular risk factor. CONCLUSIONS: This study provides reassuring data regarding the risks of MACEs and VTEs in patients initiating a JAKi versus adalimumab, including patients at high risk of cardiovascular diseases.
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Antirreumáticos , Artritis Reumatoide , Inhibidores de las Cinasas Janus , Tromboembolia Venosa , Humanos , Femenino , Adalimumab/uso terapéutico , Inhibidores de las Cinasas Janus/uso terapéutico , Tromboembolia Venosa/epidemiología , Antirreumáticos/uso terapéutico , Estudios de Cohortes , Artritis Reumatoide/tratamiento farmacológicoAsunto(s)
Artritis Psoriásica , Productos Biológicos , Enfermedades Cardiovasculares , Psoriasis , Antiinflamatorios no Esteroideos/uso terapéutico , Artritis Psoriásica/inducido químicamente , Artritis Psoriásica/tratamiento farmacológico , Productos Biológicos/efectos adversos , Enfermedades Cardiovasculares/inducido químicamente , Enfermedades Cardiovasculares/tratamiento farmacológico , Enfermedades Cardiovasculares/epidemiología , Estudios de Cohortes , Humanos , Psoriasis/tratamiento farmacológico , Talidomida/análogos & derivadosAsunto(s)
Artritis Psoriásica , Productos Biológicos , Enfermedades Cardiovasculares , Psoriasis , Antiinflamatorios no Esteroideos/uso terapéutico , Artritis Psoriásica/inducido químicamente , Artritis Psoriásica/tratamiento farmacológico , Productos Biológicos/efectos adversos , Enfermedades Cardiovasculares/inducido químicamente , Enfermedades Cardiovasculares/tratamiento farmacológico , Enfermedades Cardiovasculares/epidemiología , Estudios de Cohortes , Humanos , Psoriasis/tratamiento farmacológico , Talidomida/análogos & derivadosRESUMEN
Importance: Treatment options for psoriasis (PsO) and psoriatic arthritis (PsA) have evolved significantly throughout the era of biologics. Clinical trials are inadequate to assess the relative long-term efficacy of biologics and are often insufficient regarding safety. Objectives: To assess the long-term persistence of different biologic classes to treat PsO and PsA. Design, Setting, and Participants: This nationwide cohort study involved the administrative health care database of the French health insurance scheme linked to the hospital discharge database. All adults with PsO and PsA who were new users of biologics (not in the year before the index date) from January 1, 2015, to May 31, 2019, were included and followed up through December 31, 2019. Patients hospitalized for PsA in the PsO cohort and for PsO in the PsA cohort in the year before the index date were excluded. Data were analyzed from June 1 to October 31, 2021. Main Outcomes and Measures: Persistence was defined as the time from biologic therapy initiation to discontinuation and was estimated using the Kaplan-Meier method. Comparison of persistence by biologic class involved using propensity score-weighted Cox proportional hazards regression models and adjustment on specific systemic nonbiologics (time-dependent variables). Results: A total of 16â¯892 patients with PsO were included in the analysis (mean [SD] age, 48.5 [13.8] years; 9152 men [54.2%] men). Of these, 10â¯199 patients (60.4%) started therapy with a tumor necrosis factor (TNF) inhibitor; 3982 (23.6%), with an interleukin 12 and interleukin 23 (IL-12/23) inhibitor; and 2711 (16.0%), with an interleukin 17 (IL-17) inhibitor. An additional 6531 patients with PsA (mean [SD] age, 49.1 [12.8] years; 3565 [54.6%] women) were included; of these, 4974 (76.2%) started therapy with a TNF inhibitor; 803 (12.3%), with an IL-12/23 inhibitor; and 754 (11.5%), with an IL-17 inhibitor. Overall 3-year persistence rates were 40.9% and 36.2% for PsO and PsA, respectively. After inverse probability of treatment weighting and adjustment, the IL-17 inhibitor was associated with higher persistence compared with the TNF inhibitor for PsO (weighted hazard ratio [HR], 0.78 [95% CI, 0.73-0.83]) and PsA (weighted HR, 0.70 [95% CI, 0.58-0.85]) and compared with the IL-12/23 inhibitor for PsA (weighted HR, 0.69 [95% CI, 0.55-0.87]). No difference between the IL-17 inhibitor and IL-12/23 inhibitor for PsO was noted. The IL-12/23 inhibitor was associated with higher persistence than the TNF inhibitor for PsO (weighted HR, 0.76 [95% CI, 0.72-0.80]), with no difference observed for PsA. Conclusions and Relevance: The findings of this cohort study suggest that IL-17 inhibitors are associated with higher treatment persistence than the TNF inhibitor for PsO and PsA. Interleukin 17 inhibitors were also associated with higher persistence than the IL-12/23 inhibitor for PsA, with no difference for PsO. However, the persistence rates of all biologics remained globally low at 3 years.
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Artritis Psoriásica , Productos Biológicos , Psoriasis , Adulto , Artritis Psoriásica/tratamiento farmacológico , Productos Biológicos/efectos adversos , Estudios de Cohortes , Femenino , Humanos , Seguro de Salud , Interleucina-12 , Interleucina-17 , Masculino , Persona de Mediana Edad , Psoriasis/inducido químicamente , Psoriasis/tratamiento farmacológico , Inhibidores del Factor de Necrosis TumoralRESUMEN
Horner syndrome is a rare condition caused by a lesion of the sympathetic cervical chain. Multiple cervical disorders are associated with such lesions. Here we report the first case of Horner syndrome after cervical facet joint corticosteroid injection.
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Síndrome de Horner , Corticoesteroides/efectos adversos , Vértebras Cervicales/diagnóstico por imagen , Síndrome de Horner/inducido químicamente , Síndrome de Horner/diagnóstico , Síndrome de Horner/tratamiento farmacológico , HumanosRESUMEN
INTRODUCTION: Tumour necrosis factor inhibitor (TNFi) agents are most often the first-choice biological treatment for patients with psoriatic arthritis (PsA). When their discontinuation is needed, a switch to another TNFi or to another therapeutic class may be considered. However, data supporting one approach over another are lacking. OBJECTIVE: To compare the long-term persistence of classes of biologics in PsA patients with prior TNFi exposure. METHODS: This nationwide cohort study involved the administrative healthcare database of the French health insurance scheme linked to the hospital discharge database. We included all adults with PsA starting a second-line biological after discontinuing a TNFi during 2015-2020. Persistence was defined as the time from biological initiation to discontinuation and was estimated by the Kaplan-Meier method. Comparison of persistence by biological class was performed with Poisson regression models with time divided into 6-month intervals. RESULTS: We included 2975 patients: 1580 (53%) initiating a second TNFi, 426 (14%) an interleukin 12/23 inhibitor (IL-12/23i) and 969 (33%) an IL-17 inhibitor (IL-17i). Overall, 1-year and 3-year persistence rates were 42% and 17%, respectively. After adjustment, persistence was associated with treatment with an IL-17i (adjusted relative risk (RRa) 0.79, 95% CI 0.71 to 0.87) or IL-12/23i (RRa 0.69, 95% CI 0.61 to 0.79) vs a TNFi, with no significant difference between IL-12/23 and IL-17 inhibitors (RRa 0.88, 95% CI 0.76 to 1.02). CONCLUSIONS: Overall, this real-life study shows low persistence for all biologics at 3 years in PsA patients previously exposed to a TNFi. However, persistence was higher with an IL-17i or IL-12/23i than a TNFi.
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Antirreumáticos , Artritis Psoriásica , Productos Biológicos , Adulto , Humanos , Artritis Psoriásica/tratamiento farmacológico , Artritis Psoriásica/epidemiología , Inhibidores del Factor de Necrosis Tumoral/uso terapéutico , Antirreumáticos/uso terapéutico , Estudios de Cohortes , Interleucina-17 , Resultado del Tratamiento , Factores Biológicos/uso terapéutico , Seguro de Salud , Productos Biológicos/efectos adversos , Interleucina-12RESUMEN
OBJECTIVE: The factors contributing to long-term remission in axial SpA (axSpA) are unclear. We aimed to characterize individuals with axSpA at the 5-year follow-up to identify baseline factors associated with remission. METHODS: We included all patients from the DESIR cohort (with recent-onset axSpA) with an available Ankylosing Spondylitis Disease Activity Score-CRP (ASDAS-CRP) at 5-year follow-up. Patients in remission (ASDAS-CRP < 1.3) were compared with those with active disease by demographic, clinical, biological and imaging characteristics. A logistic model stratified on TNF inhibitor (TNFi) exposure was used. RESULTS: Overall, 111/449 patients (25%) were in remission after 5 years. Among those never exposed to TNFi, 31% (77/247) were in remission compared with 17% (34/202) of those exposed to TNFi. Patients in remission after 5 years were more likely to be male, HLA-B27+, have a lower BMI, and a higher education level. Baseline factors associated with 5-year remission in patients never exposed to TNFi included lower BASDAI [adjusted odds ratio (ORa) 0.9, 95% CI: 0.8, 0.9) and history of peripheral arthritis (ORa 2.1, 95% CI: 1.2, 5.3). In those exposed to TNFi, remission was associated with higher education level (ORa 2.9, 95% CI: 1.6, 5.1), lower enthesitis index (ORa 0.8, 95% CI: 0.7, 0.9), lower BASDAI (ORa 0.9, 95% CI: 0.9, 0.9) and lower BMI (ORa 0.8, 95% CI: 0.7, 0.9). CONCLUSION: This study highlights the difficulty in achieving 5-year remission in those with recent-onset axSpA, especially for the more active cases, despite the use of TNFi. Socio-economic factors and BMI are implicated in the outcome at 5 years.
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Espondiloartritis Axial , Espondiloartritis , Espondilitis Anquilosante , Femenino , Estudios de Seguimiento , Humanos , Masculino , Índice de Severidad de la Enfermedad , Espondiloartritis/tratamiento farmacológico , Resultado del Tratamiento , Inhibidores del Factor de Necrosis TumoralRESUMEN
OBJECTIVE: Several biological DMARDs (bDMARDs) have demonstrated anti-inflammatory effects in PsA. However, their comparative cardiovascular safety profiles remain unknown. We evaluated the risk of major adverse cardiovascular events (MACEs) in PsA patients on therapy with different classes of bDMARDs and apremilast. METHODS: This nationwide cohort study involved the administrative healthcare database of the French health insurance scheme linked to the hospital discharge database. All adults with PsA who were new users of bDMARDs/apremilast (neither in the year before the index date) during 2015-19 were included. Patients with previous cardiovascular diseases were excluded. End of follow-up was 31 December 2019. The primary endpoint was an occurrence of MACEs in a time-to-event analysis with propensity score-weighted Cox and Fine-Gray models. RESULTS: Between 2015 and 2019, we included 9510 bDMARD new users [mean age 48.5 (s.d. 12.7) years; 42% men], including 7289 starting a TNF inhibitor, 1058 an IL-12/23 inhibitor and 1163 an IL-17 inhibitor, with 1885 apremilast new users [mean age 54.0 (s.d. 12.5) years; 44% men]. MACEs occurred in 51 (0.4%) patients. After propensity score weighting, the risk of MACEs was significantly greater with IL-12/23 (weighted hazard ratio 2.0, 95% CI 1.3, 3.0) and IL-17 (weighted hazard ratio 1.9, 95% CI 1.2, 3.0) inhibitors than TNF inhibitors, with no significant increased risk with apremilast (weighted hazard ratio 1.3, 95% CI 0.8, 2.2). Similar results were observed with the Fine-Gray competing risks survival model. CONCLUSION: Analysis of a large database revealed a small overall number of MACEs, and the risk of MACEs was greater for PsA new users of IL-12/23 and IL-17 vs TNF inhibitors.
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Antirreumáticos , Artritis Psoriásica , Productos Biológicos , Enfermedades Cardiovasculares , Adulto , Antirreumáticos/efectos adversos , Artritis Psoriásica/epidemiología , Factores Biológicos/uso terapéutico , Productos Biológicos/efectos adversos , Enfermedades Cardiovasculares/inducido químicamente , Enfermedades Cardiovasculares/tratamiento farmacológico , Enfermedades Cardiovasculares/epidemiología , Estudios de Cohortes , Femenino , Humanos , Interleucina-12 , Interleucina-17 , Masculino , Persona de Mediana Edad , Talidomida/análogos & derivados , Inhibidores del Factor de Necrosis TumoralRESUMEN
IMPORTANCE: Biologics and targeted therapies, such as apremilast, are efficient treatments to manage moderate to severe psoriasis. More information about the risk of serious infection is needed for the newest treatment options in a real-world setting. OBJECTIVE: To assess the risk of serious infection among biologics and apremilast used to treat psoriasis, with etanercept as the comparator. DESIGN, SETTING, AND PARTICIPANTS: This nationwide cohort study from France involved data from the National Health Data System covering approximately 99% of the French population. All adults with psoriasis, defined as receiving at least 2 prescriptions of a topical vitamin D derivative within a 2-year period, registered in the database between January 1, 2008, and May 31, 2019, were eligible. The study population included those who were new users of biologic agents or apremilast (ie, without any prescriptions of a biologic or apremilast during the previous year). Patients with HIV infection or a history of cancer, transplant, or serious infection were excluded. End of follow-up was January 31, 2020. MAIN OUTCOME MEASURES: The primary end point was a serious infection in a time-to-event analysis using propensity score-weighted Cox proportional hazards regression models, estimating weighted hazard ratios (wHRs) and 95% CIs. RESULTS: A total of 44â¯239 new users of biologic treatment were identified (mean [SD] age, 48.4 [13.8] years; 22 866 [51.7%] men; median follow-up, 12 months [interquartile range, 7-24 months]). A total of 29â¯618 (66.9%) were prescribed a tumor necrosis factor inhibitor first, 6658 (15.0%) an interleukin (IL) 12/23 inhibitor, 4093 (9.3%) an IL-17 inhibitor, 526 (1.2%) an IL-23 inhibitor, and 3344 (7.6%) apremilast. The total number of serious infections was 1656, and the overall crude incidence rate was 25.0 (95% CI, 23.8-26.2) per 1000 person-years. The most frequent serious infections were gastrointestinal infections (645 patients [38.9%]). After adjusting for time-dependent covariables, risk of serious infections was higher for new users of adalimumab (wHR, 1.22; 95% CI, 1.07-1.38) or infliximab (wHR, 1.79; 95% CI 1.49-2.16) vs etanercept, whereas ustekinumab was associated with a lower risk of having a serious infection (wHR, 0.79; 95% CI, 0.67-0.94). Risk of serious infections was not increased for new users of IL-17 and the IL-23 inhibitor guselkumab or apremilast vs etanercept. Risk of serious infections was increased with concomitant nonsteroidal anti-inflammatory drugs or systemic corticosteroids. CONCLUSIONS AND RELEVANCE: In this cohort study of individuals with moderate to severe psoriasis, risk of serious infections was increased in new users of infliximab and adalimumab vs etanercept, whereas ustekinumab users had lower risk of having a serious infection but not new users of IL-17 and IL-23 inhibitors or apremilast. Other observational studies are needed to confirm results for the most recent drugs.