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1.
Artigo em Inglês | MEDLINE | ID: mdl-33331521

RESUMO

COVID-19 is a viral disease caused by SARS-CoV-2 that compromises the host immune response in severe cases, promoting a hyperinflammation that results in acute lung injury and multiple organs failure. In this context, patients presenting with immune-related diseases, such as Crohn's disease, affected by COVID-19, may have an uncertain prognosis. We report on a case of a young female patient with a severe Crohn's disease that presented with COVID-19 pneumonia and a favorable outcome even maintaining the use of adalimumab, TNF - alpha inhibitor and prednisone. This case raises the hypothesis that aside from prednisone, TNF-α inhibitors such as adalimumab could be used to stop the progression to COVID-19 complications by blocking the TNF-alpha-driven inflammatory process that occurs in severe COVID-19.


Assuntos
Adalimumab/uso terapêutico , Doença de Crohn/tratamento farmacológico , Prednisona/uso terapêutico , Doença de Crohn/virologia , Feminino , Humanos , Inibidores do Fator de Necrose Tumoral/uso terapêutico
2.
Eur Rev Med Pharmacol Sci ; 24(23): 12527-12535, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33336773

RESUMO

Since December 2019, an outbreak of a new coronavirus, COVID-19, infection has been taking place. At present, COVID-19 has spread to most countries worldwide. The latest evidence suggests that cytokine storm syndrome (CSS) is an important cause of the transition from mild to critical pneumonia and critically ill patients' death. The sudden exacerbation of COVID-19 may be related to a cytokine storm. Therefore, early identification and active treatment of CSS may play very important roles in improving the patients' prognosis, and these tasks are given attention in the current treatment of new Coronavirus pneumonia. However, there is still no specific medicine for this purpose. This article reviews cytokine storms and conducts an exploratory review of pharmacotherapy for cytokine storms to provide a reference for clinical treatment.


Assuntos
/imunologia , Síndrome da Liberação de Citocina/imunologia , Miocardite/imunologia , /metabolismo , Anticorpos Monoclonais Humanizados/uso terapêutico , Antioxidantes/uso terapêutico , Apoptose , Fator Natriurético Atrial/uso terapêutico , Azetidinas/uso terapêutico , Compostos de Benzil/uso terapêutico , Síndrome da Liberação de Citocina/tratamento farmacológico , Inibidores Enzimáticos/uso terapêutico , Glucocorticoides/uso terapêutico , Glicoproteínas/uso terapêutico , Humanos , Hipóxia/metabolismo , Hipóxia/terapia , Proteína Antagonista do Receptor de Interleucina 1/uso terapêutico , Isquemia Miocárdica/metabolismo , Miocardite/metabolismo , Miocardite/terapia , Miócitos Cardíacos/metabolismo , Estresse Oxidativo , Oxigenoterapia , Respiração Artificial , Moduladores do Receptor de Esfingosina 1 Fosfato/uso terapêutico , Inibidores da Tripsina/uso terapêutico , Inibidores do Fator de Necrose Tumoral/uso terapêutico , alfa-Metiltirosina/uso terapêutico
3.
Medicine (Baltimore) ; 99(43): e22626, 2020 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-33120751

RESUMO

RATIONALE: Paradoxical reaction/immune reconstitution inflammatory syndrome is common in patients with central nervous system tuberculosis. Management relies on high-dose corticosteroids and surgery when feasible. PATIENT CONCERN: We describe 2 cases of HIV-negative patients with corticosteroid-refractory paradoxical reactions of central nervous system tuberculosis. DIAGNOSES: The 2 patients experienced clinical impairment shortly after starting therapy for TB, and magnetic resonance imaging showed the presence of tuberculomas, leading to the diagnosis of a paradoxical reaction. INTERVENTIONS: We added infliximab, an anti-tumor necrosis factor (TNF)-alpha monoclonal antibody, to the dexamethasone. OUTCOMES: Both patients had favorable outcomes, 1 achieving full recovery but 1 suffering neurologic sequelae. LESSONS: Clinicians should be aware of the risk of paradoxical reactions/immune reconstitution inflammatory syndrome when treating patients with tuberculosis of the central nervous system and should consider the prompt anti-TNF-α agents in cases not responding to corticosteroids.


Assuntos
Encéfalo/efeitos dos fármacos , Tuberculose do Sistema Nervoso Central/tratamento farmacológico , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Adulto , Encéfalo/diagnóstico por imagem , Encéfalo/imunologia , Encéfalo/patologia , Feminino , Humanos , Síndrome Inflamatória da Reconstituição Imune/etiologia , Síndrome Inflamatória da Reconstituição Imune/patologia , Masculino , Pessoa de Meia-Idade , Tuberculose do Sistema Nervoso Central/complicações , Adulto Jovem
4.
Medicine (Baltimore) ; 99(41): e22668, 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33031332

RESUMO

The aim of this study was to investigate the relationship between long-term spinal mobility improvements and early disease activity changes or achievement of clinical response criteria in patients with ankylosing spondylitis (AS) treated with tumor necrosis factor (TNF-α) blockers.This retrospective study included 112 patients with AS treated with TNF-α blockers for up to 33 months. The paired t-test was used to compare outcome measures between visits. The correlation between disease activity changes and metrological improvements was analyzed using cumulative probability plots, Spearman correlation coefficient, and canonical correlation. The difference in metrological outcomes between responders and non-responders to clinical response criteria was also examined.Metrological and disease activity outcomes improved most markedly in month 3. All disease activity outcomes and ESR from baseline to month 3 (3-month) were significantly correlated with the Bath Ankylosing Spondylitis Metrology Index (BASMI10) improvements from baseline to month 33 (33-month). The 3-month changes in ankylosing spondylitis disease activity score (ASDAS-CRP) and patient's global assessment showed a significant correlation with the 33-month changes in chest expansion. Only responders according to ASDAS major improvement at month 3 demonstrated significant 33-month improvements in both BASMI10 and chest expansion, compared to non-responders. Responders according to Assessment of Spondylo Arthritis international Society 40 at month 3 showed significant 33-month improvements in BASMI10, but not chest expansion, compared to non-responders.The degree of early changes in disease activity outcomes influenced the extent of long-term metrological improvements in AS treated with TNF-α blockers. Additionally, the achievement of ASDAS- major improvement at month 3 predicted significant metrological improvements throughout long-term TNF-α-blocker therapy.


Assuntos
Espondilite Anquilosante/tratamento farmacológico , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Índice de Gravidade de Doença , Coluna Vertebral/efeitos dos fármacos , Inibidores do Fator de Necrose Tumoral/farmacologia
5.
Clin Rheumatol ; 39(12): 3529-3531, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33011932
6.
Medicine (Baltimore) ; 99(35): e21827, 2020 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-32871905

RESUMO

To retrospectively evaluate initial tumor necrosis factor inhibitor (TNFi) failure patients for clinical predictors of response to a 2nd TNFi in our 4282 rheumatoid arthritis (RA) patient database.A cross-sectional retrospective manual chart review of the electronic health record (EHR) was performed on 322 "real world" RA patients who were prescribed 2 TNFis. Response to TNFi was determined by the treating provider who had real time Clinical Disease Activity Index (CDAI) scores to inform treatment decisions. Age, gender, body mass index (BMI), insurance provider, duration of disease, cyclic citrullinated peptide antibody (CCP) and rheumatoid factor (RF) positivity, concomitant disease modifying anti-rheumatic drug therapy, length of time between diagnosis and start of 1st and 2nd TNFi, transient efficacy of 1st TNFi (defined as response to TNFi at 3 months but later lost response), and reason for discontinuation of 1st TNFi were analyzed. A multivariable logistic regression model was used to model response to a 2nd TNFi.Response proportions to the 2nd TNFi were greater in females (161/223, 72.2% response female vs 41/75, 54.7% male, P < .01), those who began their 1st TNFi within 3 months of their RA diagnosis, and in RF+ patients (123/170, 72.4% response seropositive vs 66/110, 60.0% seronegative, P < .03). The higher female response rate was independent of age, BMI, and seropositivity.In RA patients who failed an initial TNFi, female patients and patients with RF+ were more likely to have a clinical response to a 2nd TNFi. In the absence of these predictors, stronger consideration for choosing a biologic with an alternative mechanism of action might be given when the 1st TNFi fails.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Anticorpos Anti-Proteína Citrulinada/sangue , Artrite Reumatoide/sangue , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fator Reumatoide/sangue , Fatores Sexuais , Tempo para o Tratamento
7.
Clin Rheumatol ; 39(11): 3237-3244, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32892311

RESUMO

The outbreak of coronavirus in the world has led to an uncertainty about treatment of patients with autoimmune disorders because of their weakened immune system coupled with immunosuppressive agents they take which predisposes them to a host of infections. Data on COVID-19 patients with underlying rheumatological diseases has been emerging mostly in the form of small case series and one global registry. From these data, it seems like our patients, although immunosuppressed, are not particularly susceptible to the coronavirus infection and if infected, do not have significantly worse outcomes than other patients. In fact, drugs like hydroxychloroquine, dexamethasone, and tocilizumab have been studied for treatment of COVID-19. However, this is only preliminary data, and since a few parts of the world are still grappling with the pandemic at its peak, we need to be equipped on how to protect and manage our immunosuppressed patients. Published evidence to guide treatment decisions are lacking and doubts regarding continuation and initiation of immunosuppressants remain. Rheumatoid arthritis (RA) is the most common immune-mediated disorder in COVID-19 patients, and in this review, we discuss how the commonly used drugs in RA alter the patients' susceptibility to this infection. The review also summarizes the recommendations from the major bodies on how to manage this disease in these times. Key Points • Patients on immunosuppressive medications are not found to be at a greatly increased risk of acquiring COVID-19 infection. • Patients doing well on a stable dose of steroid and/or Disease-Modifying Antirheumatic Drugs (DMARDs) should be allowed to continue the same unless they get infected in which case, temporary stoppage of methotrexate and leflunomide may be considered. • Initiation of high-dose steroids, DMARDs, and biologics, if the clinical situation demands so, can be done. • Maintenance biologic therapy for stable patients should be individualized by the treating physician.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Infecções por Coronavirus , Glucocorticoides/uso terapêutico , Pandemias , Pneumonia Viral , Anti-Inflamatórios não Esteroides/uso terapêutico , Betacoronavirus , Produtos Biológicos/uso terapêutico , Desprescrições , Gerenciamento Clínico , Humanos , Inibidores do Fator de Necrose Tumoral/uso terapêutico
8.
Ann Rheum Dis ; 79(11): 1393-1399, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32769150

RESUMO

OBJECTIVES: To describe patients with autoimmune inflammatory rheumatic diseases (AIRD) who had COVID-19 disease; to compare patients who required hospital admission with those who did not and assess risk factors for hospital admission related to COVID-19. METHODS: An observational longitudinal study was conducted during the pandemic peak of severe acute respiratory syndrome coronavirus 2 (1 March 2020 to 24 April). All patients attended at the rheumatology outpatient clinic of a tertiary hospital in Madrid, Spain with a medical diagnosis of AIRD and with symptomatic COVID-19 were included. The main outcome was hospital admission related to COVID-19. The covariates were sociodemographic, clinical and treatments. We ran a multivariable logistic regression model to assess risk factors for the hospital admission. RESULTS: The study population included 123 patients with AIRD and COVID-19. Of these, 54 patients required hospital admission related to COVID-19. The mean age on admission was 69.7 (15.7) years, and the median time from onset of symptoms to hospital admission was 5 (3-10) days. The median length of stay was 9 (6-14) days. A total of 12 patients died (22%) during admission. Compared with outpatients, the factors independently associated with hospital admission were older age (OR: 1.08; p=0.00) and autoimmune systemic condition (vs chronic inflammatory arthritis) (OR: 3.55; p=0.01). No statistically significant findings for exposure to disease-modifying antirheumatic drugs were found in the final model. CONCLUSION: Our results suggest that age and having a systemic autoimmune condition increased the risk of hospital admission, whereas disease-modifying antirheumatic drugs were not associated with hospital admission.


Assuntos
Doenças Autoimunes/epidemiologia , Infecções por Coronavirus/terapia , Hospitalização/estatística & dados numéricos , Pneumonia Viral/terapia , Doenças Reumáticas/epidemiologia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Assistência Ambulatorial , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/epidemiologia , Doenças Autoimunes/tratamento farmacológico , Betacoronavirus , Diabetes Mellitus/epidemiologia , Feminino , Glucocorticoides/uso terapêutico , Cardiopatias/epidemiologia , Humanos , Hipertensão/epidemiologia , Tempo de Internação/estatística & dados numéricos , Estudos Longitudinais , Pneumopatias/epidemiologia , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/epidemiologia , Masculino , Pessoa de Meia-Idade , Doença Mista do Tecido Conjuntivo/tratamento farmacológico , Doença Mista do Tecido Conjuntivo/epidemiologia , Análise Multivariada , Pandemias , Polimialgia Reumática/tratamento farmacológico , Polimialgia Reumática/epidemiologia , Fatores de Proteção , Doenças Reumáticas/tratamento farmacológico , Fatores de Risco , Fatores Sexuais , Síndrome de Sjogren/tratamento farmacológico , Síndrome de Sjogren/epidemiologia , Espanha/epidemiologia , Espondiloartropatias/tratamento farmacológico , Espondiloartropatias/epidemiologia , Inibidores do Fator de Necrose Tumoral/uso terapêutico
9.
Rheumatol Int ; 40(9): 1353-1360, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32654078

RESUMO

As of June 10th 2020 about 7.2 million individuals have tested positive for, and more than 410,000 have died due to COVID-19. In this review we outline the pathophysiology that underpins the potential use of anti-rheumatic therapies for severe COVID-19 infection and summarize the current evidence regarding the risk and outcome of COVID-19 in patients with systemic autoimmune diseases. Thus far there is no convincing evidence that any disease-modifying anti-rheumatic drug (conventional synthetic, biologic or targeted synthetic) including hydroxychloroquine, may protect against severe COVID-19 infection; answers about their possible usefulness in the management of the cytokine storm associated with severe COVID-9 infection will only arise from ongoing randomized controlled trials. Evidence on COVID-19 risk and outcome in patients with systemic autoimmune diseases is extremely limited; thus, any conclusions would be unsafe and should be seen with great caution. At present, the risk and severity (hospitalization, intensive care unit admission and death) of COVID-19 infection in people with autoimmune diseases do not appear particularly dissimilar to the general population, with the possible exception of hospitalization in patients exposed to high glucocorticoid doses. At this stage it is impossible to draw any conclusions for differences in COVID-19 risk and outcome between different autoimmune diseases and between the various immunomodulatory therapies used for them. More research in the field is obviously required, including as a minimum careful and systematic epidemiology and appropriately controlled clinical trials.


Assuntos
Antirreumáticos/uso terapêutico , Doenças Autoimunes/tratamento farmacológico , Infecções por Coronavirus/tratamento farmacológico , Síndrome da Liberação de Citocina/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Anticorpos Monoclonais Humanizados/uso terapêutico , Doenças Autoimunes/epidemiologia , Doenças Autoimunes/imunologia , Betacoronavirus , Comorbidade , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/imunologia , Síndrome da Liberação de Citocina/imunologia , Humanos , Inibidores de Janus Quinases/uso terapêutico , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/imunologia , Fatores de Risco , Índice de Gravidade de Doença , Inibidores do Fator de Necrose Tumoral/uso terapêutico
10.
Aliment Pharmacol Ther ; 52(4): 669-681, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32656800

RESUMO

BACKGROUND: Direct comparisons are lacking between vedolizumab and tumour necrosis factor (TNF)-antagonist therapy in Crohn's disease (CD). AIM: To compare safety and effectiveness of vedolizumab and TNF-antagonist therapy in adult CD patients. METHODS: Retrospective observational cohort (May 2014-December 2017) propensity score-weighted comparison of vedolizumab vs TNF-antagonist therapy (infliximab, adalimumab, certolizumab) in CD. Propensity scores were weighted for age, prior treatments, disease complications, extent and severity, steroid dependence, and concomitant immunosuppressive drug use. The primary outcome was comparative risk for infections or non-infectious serious adverse events (requiring antibiotics, antivirals, antifungals, hospitalisation, or treatment discontinuation, or resulting in death). Secondary comparative effectiveness outcomes were clinical remission (resolution of CD-related symptoms), steroid-free clinical remission and endoscopic remission (absence of ulcers/erosions). RESULTS: We included 1266 patients (n = 659 vedolizumab). Rates of non-infectious serious adverse events (odds ratio [OR] 0.072, 95% confidence interval [CI] 0.012-0.242), but not serious infections (OR 1.183, 95% CI 0.786-1.795), were significantly lower with vedolizumab vs TNF-antagonist therapy. Safety comparisons for non-infectious serious adverse events remained significant after adjusting for differences in duration of exposure. No significant difference was observed between vedolizumab and TNF-antagonist therapy for clinical remission (hazard ratio [HR] 0.932, 95% CI 0.707-1.228), steroid-free clinical remission (HR 1.250, 95% CI 0.677-2.310) or endoscopic remission (HR 0.827, 95% CI 0.595-1.151). TNF-antagonist therapy was associated with higher treatment persistence compared with vedolizumab. CONCLUSIONS: There was a lower risk of non-infectious serious adverse events, but not serious infections, with vedolizumab vs TNF-antagonist therapy, with no significant difference for achieving disease remission.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Doença de Crohn/tratamento farmacológico , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Adalimumab/uso terapêutico , Adulto , Anticorpos Monoclonais Humanizados/efeitos adversos , Certolizumab Pegol/uso terapêutico , Estudos de Coortes , Doença de Crohn/epidemiologia , Feminino , Humanos , Infliximab/uso terapêutico , Pessoa de Meia-Idade , Indução de Remissão , Estudos Retrospectivos , Resultado do Tratamento , Inibidores do Fator de Necrose Tumoral/efeitos adversos , Adulto Jovem
11.
Ann Rheum Dis ; 79(10): 1327-1332, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32660979

RESUMO

OBJECTIVES: Tumour necrosis factor inhibitors (TNFis) have been suggested to slow radiographic progression in patients with ankylosing spondylitis. However, limitations such as variations in disease activity, complex drug administration and short follow-up duration make it difficult to determine the effect of TNFis on radiographic progression. The aim of the study was to investigate whether long-term treatment with TNFis can reduce radiographic progression in patients with ankylosing spondylitis using 18-year longitudinal real-world data. METHODS: This retrospective study was conducted between January 2001 and December 2018 at a single centre. Among the 1280 patients whose electronic medical records were reviewed, data of 595 patients exposed to TNFis at least once were included. Among them, time intervals of TNFi exposure or non-exposure were determined in 338 patients ('on the TNFis' or 'off the TNFis' intervals, respectively). The difference in the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) change rate between 'on the TNFis' and 'off the TNFis' intervals was investigated. RESULTS: We obtained 2364 intervals of 338 patients (1281 'on the TNFis' and 1083 'off the TNFis' intervals). In the marginal structural model for inverse probability of treatment weighting, the change rate of mSASSS significantly decreased with the use of TNFis (ß=-0.112, p=0.004), and the adjusted mSASSS changes were 0.848 and 0.960 per year during 'on the TNFis' and 'off the TNFis' intervals, respectively. CONCLUSION: Compared with treatment without TNFis, treatment with TNFis slowed radiologic progression significantly.


Assuntos
Espondilite Anquilosante/tratamento farmacológico , Espondilite Anquilosante/patologia , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Adulto , Progressão da Doença , Feminino , Humanos , Masculino , Estudos Retrospectivos
12.
Rheumatol Int ; 40(9): 1423-1431, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32661928

RESUMO

Concerns regarding the comorbidity as a significant risk factor for Coronavirus Disease-2019 (COVID-19), gave rise to an urgent need for studies evaluating patients with chronic conditions such as autoinflammatory diseases (AIDs). We prepared a web-based survey investigating the clinical findings and contact histories among pediatric patients with AIDs. Confirmed COVID-19 cases, patients with contact history and those with symptoms which were highly suggestive of COVID-19 were called via phone or recruited to a video or face to face appointment. Data of AIDs were obtained from their medical records, retrospectively. Laboratory and screening findings were confirmed by our national health registry website. There were 404 patients (217 female) eligible for the enrollment. During pandemic, 375 (93%) were on colchicine treatment and 48 (11.8%) were receiving biologic treatment. Twenty-four out of 404 patients were admitted to hospital due to COVID-19 suspicion. Severe acute respiratory syndrome coronavirus-2 (SARS CoV-2) was identified through rhinopharyngeal swabs in seven patients, six of whom were only on colchicine treatment. Only one patient with no finding of any severe respiratory complications was hospitalized. All of seven patients recovered completely. Among patients on biologic drugs, neither a symptom nor a positive polymerase chain reaction test for COVID 19 was detected. In conclusion, pediatric patients with AIDs, those receiving biologic treatment and/or colchicine, may not be at increased risk for neither being infected nor the severe disease course.


Assuntos
Colchicina/uso terapêutico , Infecções por Coronavirus/fisiopatologia , Doenças Hereditárias Autoinflamatórias/tratamento farmacológico , Pneumonia Viral/fisiopatologia , Moduladores de Tubulina/uso terapêutico , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Adalimumab/uso terapêutico , Adolescente , Anticorpos Monoclonais Humanizados/uso terapêutico , Betacoronavirus , Produtos Biológicos , Criança , Pré-Escolar , Estudos de Coortes , Infecções por Coronavirus/complicações , Infecções por Coronavirus/terapia , Síndromes Periódicas Associadas à Criopirina/complicações , Síndromes Periódicas Associadas à Criopirina/tratamento farmacológico , Etanercepte/uso terapêutico , Febre Familiar do Mediterrâneo/complicações , Febre Familiar do Mediterrâneo/tratamento farmacológico , Feminino , Doenças Hereditárias Autoinflamatórias/complicações , Humanos , Lactente , Proteína Antagonista do Receptor de Interleucina 1/uso terapêutico , Masculino , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/terapia , Turquia , Adulto Jovem
13.
Am J Gastroenterol ; 115(10): 1698-1706, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32701731

RESUMO

INTRODUCTION: Biologic agents including infliximab are effective but costly therapies in the management of inflammatory bowel disease (IBD). Home infliximab infusions are increasingly payer-mandated to minimize infusion-related costs. This study aimed to compare biologic medication use, health outcomes, and overall cost of care for adult and pediatric patients with IBD receiving home vs office- vs hospital-based infliximab infusions. METHODS: Longitudinal patient data were obtained from the Optum Clinformatics Data Mart. The analysis considered all patients with IBD who received infliximab from 2003 to 2016. Primary outcomes included nonadherence (≥2 infliximab infusions over 10 weeks apart in 1 year) and discontinuation of infliximab. Secondary outcomes included outpatient corticosteroid use, follow-up visits, emergency room visits, hospitalizations, surgeries, and cost outcomes (out-of-pocket costs and annual overall cost of care). RESULTS: There were 27,396 patients with IBD (1,839 pediatric patients). Overall, 5.7% of patients used home infliximab infusions. These patients were more likely to be nonadherent compared with both office-based (22.2% vs 19.8%; P = .044) and hospital-based infusions (22.2% vs 21.2%; P < .001). They were also more likely to discontinue infliximab compared with office-based (44.7% vs 33.7%; P < .001) or hospital-based (44.7% vs 33.4%; P < .001) infusions. On Kaplan-Meier analysis, the probabilities of remaining on infliximab by day 200 of therapy were 64.4%, 74.2%, and 79.3% for home-, hospital-, and office-based infusions, respectively (P < .001). Home infliximab patients had the highest corticosteroid use (cumulative corticosteroid days after IBD diagnosis: home based, 238.2; office based, 189.7; and hospital based, 208.5; P < .001) and the fewest follow-up visits. Home infusions did not decrease overall annual care costs compared with office infusions ($49,149 vs $43,466, P < .001). DISCUSSION: In this analysis, home infliximab infusions for patients with IBD were associated with suboptimal outcomes including higher rates of nonadherence and discontinuation of infliximab. Home infusions did not result in significant cost savings compared with office infusions.


Assuntos
Assistência Ambulatorial/métodos , Terapia por Infusões no Domicílio/métodos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Infliximab/uso terapêutico , Adesão à Medicação/estatística & dados numéricos , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Adolescente , Corticosteroides/uso terapêutico , Adulto , Idoso , Assistência Ambulatorial/economia , Criança , Estudos de Coortes , Colite Ulcerativa/tratamento farmacológico , Redução de Custos , Doença de Crohn/tratamento farmacológico , Serviço Hospitalar de Emergência/estatística & dados numéricos , Feminino , Custos de Cuidados de Saúde , Gastos em Saúde , Terapia por Infusões no Domicílio/economia , Hospitalização/estatística & dados numéricos , Humanos , Infusões Intravenosas , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Visita a Consultório Médico/estatística & dados numéricos , Consultórios Médicos , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
15.
Ann Rheum Dis ; 79(7): 988-990, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32503857
16.
Z Rheumatol ; 79(6): 574-577, 2020 Aug.
Artigo em Alemão | MEDLINE | ID: mdl-32514854

RESUMO

A case with rheumatoid arthritis and insufficient compensation under disease-modifying combined long-term therapy with methotrexate and leflunomide is reported. After recovery from a COVID-19 infection, a tumor necrosis factor (TNF) inhibitor therapy was initiated. Until now no reactivation of the COVID-19 infection with positive SARS-CoV­2 antibody status has occurred.


Assuntos
Anticorpos Antivirais/sangue , Artrite Reumatoide/tratamento farmacológico , Terapia Biológica , Infecções por Coronavirus/complicações , Pneumonia Viral/complicações , Artrite Reumatoide/virologia , Betacoronavirus , Humanos , Leflunomida/uso terapêutico , Metotrexato/uso terapêutico , Pandemias , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Ativação Viral
18.
Expert Opin Pharmacother ; 21(13): 1527-1536, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32515665

RESUMO

INTRODUCTION: The introduction of JAKs inhibitors for the treatment of rheumatoid arthritis represents a promising new era in the management of the disease. New compounds under investigation, like upadacitinib, with greater selectivity for JAK1 inhibition have recently been approved for the treatment of adults with moderately to severely active rheumatoid arthritis who have had an inadequate response or intolerance to conventional synthetic disease-modifying antirheumatic drugs. AREAS COVERED: Herein, the authors review the pharmacological data, the therapeutic efficacy, and safety data of upadacitinib before providing the reader with their critical evaluation and future perspectives. EXPERT OPINION: Upadacitinib was able to accomplish all the primary and secondary end points in most of the trials, with a safety profile that is similar to the other JAK inhibitors. It has also demonstrated superiority over a tumor necrosis factor inhibitor and data on new indications is also favorable. Upadacitinib is a promising new drug for the treatment of rheumatoid arthritis. GLOSSARY: Adalimumab: ADA; American College of Rheumatology: ACR; Assessment of Spondylarthritis International Society 40: ASAS40; Ankylosis Spondylitis: AS; Area under the Curve: AUC; Biological Disease-modifying arthritis drugs: bDMARDs; Clinical disease activity index: CDAI; C Reactive Protein: CRP; Conventional Synthetic Disease-modifying arthritis drugs: csDMARDs; Deep Venous Thrombosis: DVT; Disease arthritis score: DAS.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Inibidores de Janus Quinases/uso terapêutico , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Adulto , Artrite Reumatoide/enzimologia , Artrite Reumatoide/imunologia , Proteína C-Reativa/metabolismo , Quimioterapia Combinada , Humanos , Espondilartrite/tratamento farmacológico , Espondilite Anquilosante/tratamento farmacológico , Resultado do Tratamento
19.
Indian J Gastroenterol ; 39(2): 176-185, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32483692

RESUMO

BACKGROUND: Evidence supports therapeutic drug monitoring (TDM) in improving efficacy and cost-effectiveness of anti-TNF therapy in inflammatory bowel disease (IBD). Data on perceptions and barriers to TDM use are limited and no data are available from India. Our objective was to assess clinicians' attitudes and barriers to TDM use in IBD. METHODS: A 16-question survey was distributed to members of the Indian Society of Gastroenterology. Information on clinician characteristics, demographics, use and barriers towards TDM with anti-TNFs was collected. Logistic regression was used to predict factors influencing TDM use. RESULTS: Two hundred and forty-two respondents participated (92.5% male); 83% were consultant gastroenterologists. Of 104 respondents meeting inclusion criteria (treating > 5 IBD patients and at least 1 with an anti-TNF per month), complete responses were available for 101 participants. TDM was utilized by 20% (n = 20) of respondents. Of them, 89.5% (n = 17) used TDM for secondary loss of response; 73.7% (n = 14) for primary non-response and 5.3% (n = 1) proactively. Barriers to TDM use were cost (71.2%), availability (67.8%), time lag in results (58.7%) and the perception that TDM is time-consuming (45.7%). Clinicians treating > 30 IBD patients were more likely to check TDM (OR = 4.9, p = 0.02). Of 81 respondents not using TDM, 97.5% (n = 79) would do so if all the barriers were removed. CONCLUSION: Significant barriers to TDM use were availability, cost and time lag for results. If these barriers were removed, almost all the clinicians would use TDM at least reactively and 25% would use proactively. There is an urgent need to address these barriers and optimize anti-TNF therapy for optimal outcomes.


Assuntos
Monitoramento de Medicamentos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Infliximab/uso terapêutico , Utilização de Procedimentos e Técnicas/estatística & dados numéricos , Inquéritos e Questionários , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Adulto , Idoso , Análise Custo-Benefício , Monitoramento de Medicamentos/estatística & dados numéricos , Feminino , Humanos , Índia/epidemiologia , Doenças Inflamatórias Intestinais/economia , Infliximab/economia , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Inibidores do Fator de Necrose Tumoral/economia
20.
Medicine (Baltimore) ; 99(26): e20458, 2020 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-32590730

RESUMO

INTRODUCTION: Targeted biologic therapies demonstrate similar efficacies in rheumatoid arthritis despite distinct mechanisms of action. They also exhibit a ceiling effect, with 10% to 20% of patients achieving remission in clinical trials. None of these therapies target synovial fibroblasts, which drive and maintain synovitis. Seliciclib (R-roscovitine) is an orally available cyclin-dependent kinase inhibitor that suppresses fibroblast proliferation, and is efficacious in preclinical arthritis models. We aim to determine the toxicity and preliminary efficacy of seliciclib in combination with biologic therapies, to inform its potential as an adjunctive therapy in rheumatoid arthritis. METHODS AND ANALYSIS: TRAFIC is a non-commercial, multi-center, rolling phase Ib/IIa trial investigating the safety, tolerability, and efficacy of seliciclib in patients with moderate to severe rheumatoid arthritis receiving biologic therapies. All participants receive seliciclib with no control arm. The primary objective of part 1 (phase Ib) is to determine the maximum tolerated dose and safety of seliciclib over 4 weeks of dosing. Part 1 uses a restricted 1-stage Bayesian continual reassessment method based on a target dose-limiting toxicity probability of 35%. Part 2 (phase IIa) assesses the potential efficacy of seliciclib, and is designed as a single arm, single stage early phase trial based on a Fleming-A'Hern design using the maximum tolerated dose recommended from part 1. The primary response outcome after 12 weeks of therapy is a composite of clinical, histological and magnetic resonance imaging scores. Secondary outcomes include adverse events, pharmacodynamic and pharmacokinetic parameters, autoantibodies, and fatigue. ETHICS AND DISSEMINATION: The study has been reviewed and approved by the North East - Tyne & Wear South Research Ethics Committee (reference 14/NE/1075) and the Medicines and Healthcare Products Regulatory Agency (MHRA), United Kingdom. Results will be disseminated through publication in relevant peer-reviewed journals and presentation at national and international conferences. TRIALS REGISTRATION: ISRCTN, ISRCTN36667085. Registered on September 26, 2014; http://www.isrctn.com/ISRCTN36667085Current protocol version: Protocol version 11.0 (March 21, 2019).


Assuntos
Artrite Reumatoide/tratamento farmacológico , Inibidores de Proteínas Quinases/administração & dosagem , Roscovitina/administração & dosagem , Abatacepte/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Ensaios Clínicos Fase II como Assunto , Ensaios Clínicos Fase III como Assunto , Quimioterapia Combinada , Humanos , Dose Máxima Tolerável , Estudos Multicêntricos como Assunto , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Reino Unido
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