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1.
Medicine (Baltimore) ; 98(38): e17110, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31567948

RESUMO

BACKGROUND: Systemic sclerosis (SSc) is a clinically complex and challenging disease, the most frequent complication of which is interstitial lung disease, which leads to a worse prognosis. In this situation, cyclophosphamide is considered the criterion standard for treatment, despite the controversies regarding its efficacy and toxicity. However, studies using rituximab (RTX) have shown that this drug may be a promising therapeutic option. The objective is to describe a protocol of a systematic review (SR) that analyzes the scientific evidence on the effects of RTX on SSc. METHODS: This protocol is guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols. The databases to be searched are PubMed, Scopus, SciELO, LILACS, ScienceDirect, Web of Science, COCHRANE, WHOLIS, PAHO, and EMBASE. The studies that would be included in SR are clinical trials that evaluate the use of RTX in patients with SSc who meet the classification criteria for the disease according to American College of Rheumatology and European League Against Rheumatism (2013) and/or LeRoy criteria will be included in the SR. The data to be extracted are related to the characteristics of the studies: authors, year of publication, study location, type of study, sample size and age, patient characteristics, duration of intervention, therapeutic scheme, follow-up time, main variables, and main results. RESULTS: In our study, we hope to find articles presenting new evidence supporting treatment of SSc with RTX. CONCLUSIONS: The SR will present results of scientific evidence for the effects of RTX in SSc. We hope that the results could strengthen clinical decisions for the best treatment of SSc and guide future researches. PROSPERO REGISTRATION NUMBER: CRD42019132018.


Assuntos
Antirreumáticos/uso terapêutico , Rituximab/uso terapêutico , Escleroderma Sistêmico/tratamento farmacológico , Antirreumáticos/administração & dosagem , Protocolos Clínicos , Humanos , Rituximab/administração & dosagem , Revisão Sistemática como Assunto
2.
Top Curr Chem (Cham) ; 377(5): 28, 2019 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-31563994

RESUMO

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease that primarily affects the joints, with the main clinical manifestations being chronic, symmetrical, and peripheral multi-joint inflammatory lesions. Drugs, including nonsteroidal anti-inflammatory drugs (NSAIDs), glucocorticoids (GCs), disease-modifying anti-rheumatic drugs (DMARDs), and biologics play a very important role in the treatment of RA. Of these, the most commonly used are chemical drugs, such as NSAIDs, GCs, and DMARDs. In recent years, a number of new compounds have emerged for the treatment of RA, such as SYK inhibitors, JAK inhibitors, NSAID-CAI drugs, and Syk/PDGFR-α/c-Kit inhibitors. In this review, we summarize the most recently developed anti-RA chemical drugs and discuss the synthesis and biological activities of these various new compounds.


Assuntos
Antirreumáticos/síntese química , Antirreumáticos/farmacologia , Artrite Reumatoide/tratamento farmacológico , Animais , Antirreumáticos/química , Antirreumáticos/uso terapêutico , Humanos , Estrutura Molecular
3.
Internist (Berl) ; 60(10): 1059-1073, 2019 Oct.
Artigo em Alemão | MEDLINE | ID: mdl-31471629

RESUMO

Large-vessel vasculitis includes giant cell arteritis (GCA) and Takayasu arteritis (TA). GCA can affect persons from the age of 50 years and is more frequent among women. The disease course generally begins with an acute phase, with patients feeling very unwell and experiencing temporal headaches. Rapid diagnosis and treatment are necessary to reduce the risk of blindness. A suspected diagnosis must be confirmed by imaging, histology is optional. Initial treatment comprises oral prednisone. Recent studies have demonstrated inhibition of interleukin­6 with tocilizumab (TCZ) to be highly effective. Alternatively, methotrexate can be administered in a steroid-sparing approach. In contrast, TA onset is generally during childhood or adolescence, and begins with moderate systemic inflammation. The aorta and its main branches are affected. Treatment comprises steroids, disease-modifying antirheumatic drugs, and the tumor necrosis factor inhibitor infliximab or TCZ.


Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Antirreumáticos/administração & dosagem , Arterite de Células Gigantes/tratamento farmacológico , Imunossupressores/administração & dosagem , Arterite de Takayasu/tratamento farmacológico , Idoso , Anticorpos Monoclonais Humanizados/uso terapêutico , Antirreumáticos/uso terapêutico , Feminino , Células Gigantes , Glucocorticoides/administração & dosagem , Glucocorticoides/uso terapêutico , Humanos , Metotrexato/administração & dosagem , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Prednisona/administração & dosagem , Prednisona/uso terapêutico , Resultado do Tratamento
4.
Internist (Berl) ; 60(10): 1036-1042, 2019 Oct.
Artigo em Alemão | MEDLINE | ID: mdl-31485714

RESUMO

BACKGROUND: Monoclonal antibodies and fusion proteins were introduced into clinical rheumatology 20 years ago. Nowadays they are an established component of modern internal medical practice. OBJECTIVE: This article gives an overview of the breadth of biologics currently in clinical use. MATERIAL AND METHODS: Evaluation of published approval studies and guideline recommendations, discussion of the immunological principles and targets in the treatment with biologics. RESULTS: Monoclonal antibodies and fusion proteins for influencing cytokine signals, T­cell costimulation and B­cell function are the most important innovations in the treatment of rheumatological diseases. Nowadays they are indispensible for the treatment of moderate and severe disease courses of rheumatoid arthritis, spondylarthropathies and vasculitides. CONCLUSION: Although a cure or permanent freedom from symptoms in rheumatological autoimmune diseases is still not possible, much more favorable disease courses with less long-term limitations can be achieved by the early administration of biologics.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Produtos Biológicos/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Humanos , Infliximab/uso terapêutico , Reumatologia , Rituximab/uso terapêutico
5.
Harefuah ; 158(9): 595-600, 2019 Sep.
Artigo em Hebraico | MEDLINE | ID: mdl-31507112

RESUMO

INTRODUCTION: Rituximab, a monoclonal antibody against CD20 positive B cell, depletes these cells peripherally, and is a successful treatment in rheumatoid arthritis (RA). It is the second efficacious biologic to be established in the treatment of RA after TNFα blockers. Eighteen years of global experience from diverse clinical trials and from "real world" data, have demonstrated clinical efficacy in various disease scenarios and patient populations - short and long disease duration, methotrexate naïve patients and those with incomplete response to methotrexate, biologic naïve patients and those with incomplete response to previous biologics. Moreover, it has demonstrated the inhibition of radiographic progression. It seems to be most efficacious in seropositive patients. Despite vast experience, the need for concomitant traditional disease-modifying anti rheumatic drugs (DMARD), the optimal retreatment dose, and the favored retreatment interval remain somewhat uncertain. The recommended dosage is 1000 mg, administered twice, with a 2 weeks interval, although in some cases, a reduced dosage of 500 mg, administered twice may be considered. The safety profile of rituximab includes mainly infusion-related reactions, which are usually mild. A small risk of major infections has remained stable over time and repeated courses. Opportunistic infections are infrequent. Nevertheless, reactivation of hepatitis B is still a concern. Tuberculosis, malignancies, cardiovascular events and deterioration of interstitial lung disease do not appear to be increased. Since rituximab severely impairs the humoral response to vaccinations, they should be administered prior to treatment whenever possible. Rituximab has been a powerful addition to the large armamentarium for the treatment of RA. Rituximab is indicated in Israel as a second line biologic treatment for active RA.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Rituximab/uso terapêutico , Quimioterapia Combinada , Humanos , Israel , Metotrexato , Resultado do Tratamento
6.
Clin Exp Rheumatol ; 37(5): 862-871, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31376250

RESUMO

The latest revision of the European League Against Rheumatism (EULAR) recommendations for rheumatoid arthritis (RA) treatment maintains the indication for the combined therapy of biological disease-modifying antirheumatic drugs (bDMARDs) and targeted synthetic DMARDs (tsDMARDs), namely Jak-inhibitors as tofacitinib and baricitinib, with conventional synthetic DMARDs (csDMARDs). Moreover, the use of bDMARDs and tsDMARDs should be restricted to patients who failed to achieve an adequate response to one or more csDMARDs, in accordance with the current evidence showing the superiority of combination therapy over monotherapy. In patients who cannot use csDMARDs as comedication, IL-6 inhibitors and tsDMARDs should be preferred to other bDMARDs because they are apparently more effective as monotherapy. Registry and real-world data demonstrate that monotherapy is far more commonly used than expected based on treatment recommendations, currently being about 30% of patients with RA on bDMARD monotherapy. We review here the literature on most commonly used DMARDs in monotherapy for RA. Our review points at an increasing evidence of the potential of some bDMARDs and tsDMARDs in monotherapy, which may become a considerable and realistic option in RA patients.


Assuntos
Antirreumáticos , Artrite Reumatoide , Inibidores de Janus Quinases , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Produtos Biológicos/uso terapêutico , Quimioterapia Combinada , Humanos , Inibidores de Janus Quinases/uso terapêutico , Conduta do Tratamento Medicamentoso , Sistema de Registros , Resultado do Tratamento
7.
Z Rheumatol ; 78(6): 529-539, 2019 Aug.
Artigo em Alemão | MEDLINE | ID: mdl-31297605

RESUMO

Every patient suffering from active rheumatoid arthritis should be treated with disease-modifying antirheumatic drugs (DMARD) but methotrexate initially remains the first choice treatment. Treatment should comply with the treat-to-target principle. The therapeutic aim is remission if attainable or at least a low disease activity. Remission is defined as a simplified disease activity score index (SDAI) of ≤3.3 or as fulfilling the so-called Boolean criteria. A first evaluation of the response is due after 12 weeks. At this time there should be a measurable response defined as an improvement of at least 50% of the composite score, e.g. the DAS28. If no improvement has been achieved, treatment should be continued with either a second DMARD strategy conventionally with synthetic DMARDs (csDMARDs) or an alternative with biological (bDMARD) or targeted synthetic (tsDMARDs) DMARD, depending on whether there are risk factors for a severe disease progression. A change within bDMARDs and tsDMARDs as well as therapeutic de-escalation are both possible measures in the further course of treatment.


Assuntos
Antirreumáticos , Artrite Reumatoide , Produtos Biológicos/uso terapêutico , Metotrexato/uso terapêutico , Algoritmos , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Quimioterapia Combinada , Humanos , Guias de Prática Clínica como Assunto , Indução de Remissão , Índice de Gravidade de Doença , Resultado do Tratamento
8.
Medicine (Baltimore) ; 98(30): e16413, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31348241

RESUMO

BACKGROUND: Pain is the main symptom of patients with rheumatoid arthritis (RA). Reports of the effects of moxibustion on patients with rheumatoid arthritis have reached various conclusions. The aim of this meta-analysis was to evaluate the effect of moxibustion on pain in patients with RA. METHODS: A systematic search of MEDLINE, EMBASE, the Cochrane Library, and the Chinese databases Wan Fang Med Database, CNKI, and VIP (until November, 2018) was used to identify studies reporting pain (on a visual analogue scale (VAS)), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and rheumatoid factor (RF) levels, response rate, and the ACR50 rate in patients with RA. Results were expressed as mean difference (MD) and 95% confidence intervals (CI). RESULTS: Six studies involving 281 participants were included. Moxibustion had significant effects on pain (VAS: MD = -0.53, 95% CI [-0.94, -0.12], P =.01). Moreover, moxibustion had effects on CRP (MD = -2.84, 95% CI [-5.13, -0.55], P =.01), ESR (MD = -8.44, 95% CI ([-13.19, -3.68], P =.0005), and RF (MD = -6.39, 95% CI [-18.57, 5.79], P =.30). Additionally, it had effects on response rate (n = 249, RR = 1.26, 95% CI [1.11, 1.43], P =.0004) and ACR50 rate (n = 140, RR = 1.44, 95% CI [1.11, 1.88], P =.007). CONCLUSION: We found that moxibustion with Western medicine therapy is superior to Western medicine therapy alone for pain in patients with RA. Moxibustion had significant effects on pain in patients with RA, but the effects of moxibustion on inflammatory factors in RA were unclear.


Assuntos
Artrite Reumatoide/terapia , Moxibustão/métodos , Manejo da Dor/métodos , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Sedimentação Sanguínea , Proteína C-Reativa/análise , Terapia Combinada , Humanos , Medição da Dor , Ensaios Clínicos Controlados Aleatórios como Assunto , Fator Reumatoide/sangue
9.
Anticancer Res ; 39(7): 3945-3947, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31262925

RESUMO

BACKGROUND/AIM: Malignant melanoma is a rare disease in the pediatric population and there are no recommendations regarding its management in children, while the current standard of care in metastatic or unresectable melanoma in adult patients includes immunotherapy (anti-CTLA-4 and anti-PD-1 antibodies). Advances in the management of adults with melanoma offer the prospect of promising therapeutic options for children. CASE REPORT: We describe a case of a 7-year-old patient with recurrent metastatic melanoma, for whom pembrolizumab was used as an adjuvant therapy on compassionate use basis. CONCLUSION: Due to adverse events, the treatment was discontinued after 5 months of pembrolizumab, but with 12-months of follow-up, patient remains in complete remission.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Melanoma/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias de Tecidos Moles/tratamento farmacológico , Antirreumáticos/uso terapêutico , Artrite Juvenil/induzido quimicamente , Artrite Juvenil/tratamento farmacológico , Criança , Feminino , Humanos , Metotrexato/uso terapêutico , Esteroides/uso terapêutico , Resultado do Tratamento , Uveíte/induzido quimicamente
10.
Medicine (Baltimore) ; 98(26): e15947, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31261500

RESUMO

To assess the hypothesis if tocilizumab (TCZ) is effective on disease activity, and also its effect in fatigue and other clinical and psychological disease-related factors in patients with rheumatoid arthritis (RA) treated with TCZ.A 24-week, multicenter, prospective, observational study in patients with moderate to severe RA receiving TCZ after failure or intolerance to disease-modifying antirheumatic drugs or tumor necrosis factor-alpha was conducted.Of the 122 patients included, 85 were evaluable for effectiveness (85% female, 51.9 ±â€Š12.5 years, disease duration 8.7 ±â€Š7.4 years). Mean change in C-reactive protein level from baseline to week 12 was -11.2 ±â€Š4.0 (P < .001). Mean Disease Activity Index score (DAS28) decreased from 5.5 ±â€Š1.0 at baseline to 2.7 ±â€Š1.3 (P < .001) at week 24. Mean change in Functional Assessment of Chronic Illness Therapy score was -5.4 ±â€Š11.2 points at week 24. Multiple regression analysis showed that the improvement in DAS28, sleep, and depression explained 56% and 47% of fatigue variance at week 12 and 24, respectively.Tocilizumab is effective in reducing disease activity and results in a clinically significant improvement in fatigue, pain, swollen joint count, morning stiffness, sleepiness, depression, and DAS28; the last 3 were specifically identified as factors explaining fatigue variance with the use of TCZ in RA patients.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Artrite Reumatoide/psicologia , Artrite Reumatoide/terapia , Fadiga/psicologia , Fadiga/terapia , Antirreumáticos/uso terapêutico , Artrite Reumatoide/fisiopatologia , Biomarcadores/metabolismo , Proteína C-Reativa/metabolismo , Depressão/fisiopatologia , Depressão/terapia , Fadiga/etiologia , Fadiga/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Retratamento , Sono , Resultado do Tratamento , Fator de Necrose Tumoral alfa/uso terapêutico
11.
JAMA ; 322(4): 315-325, 2019 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-31334793

RESUMO

Importance: Patients with active rheumatoid arthritis (RA) despite treatment with biologic disease-modifying antirheumatic drug (bDMARD) therapy need treatment options. Objective: To evaluate the effects of filgotinib vs placebo on the signs and symptoms of RA in a treatment-refractory population. Design, Setting, and Participants: A 24-week, randomized, placebo-controlled, multinational phase 3 trial conducted from July 2016 to June 2018 at 114 sites internationally, randomizing 449 adult patients (and treating 448) with moderately to severely active RA and inadequate response/intolerance to 1 or more prior bDMARDs. Interventions: Filgotinib, 200 mg (n = 148); filgotinib, 100 mg (n = 153); or placebo (n = 148) once daily; patients continued concomitant stable conventional synthetic DMARDs (csDMARDs). Main Outcomes and Measures: The primary end point was the proportion of patients who achieved 20% improvement in the American College of Rheumatology criteria (ACR20) at week 12. Secondary outcomes included week 12 assessments of low disease activity (disease activity score in 28 joints-C-reactive protein [DAS28-CRP] ≤3.2) and change in Health Assessment Questionnaire-Disability Index, 36-Item Short-Form Health Survey Physical Component, and Functional Assessment of Chronic Illness Therapy-Fatigue scores, as well as week 24 assessment of remission (DAS28-CRP <2.6) and adverse events. Results: Among 448 patients who were treated (mean [SD] age, 56 [12] years; 360 women [80.4%]; mean [SD] DAS28-CRP score, 5.9 [0.96]; 105 [23.4%] with ≥3 prior bDMARDs), 381 (85%) completed the study. At week 12, more patients receiving filgotinib, 200 mg (66.0%) or 100 mg (57.5%), achieved ACR20 response (placebo, 31.1%; difference vs placebo: 34.9% [95% CI, 23.5%-46.3%] and 26.4% [95% CI, 15.0%-37.9%], respectively; both P < .001), including among patients with prior exposure to 3 or more bDMARDs (70.3%, 58.8%, and 17.6%, respectively; difference vs placebo: 52.6% [95% CI, 30.3%-75.0%] for filgotinib, 200 mg, and 41.2% [95% CI, 17.3%-65.0%] for filgotinib, 100 mg; both P < .001). The most common adverse events were nasopharyngitis (10.2%) for filgotinib, 200 mg; headache, nasopharyngitis, and upper respiratory infection (5.9% each) for filgotinib, 100 mg; and RA (6.1%) for placebo. Four uncomplicated herpes zoster cases and 1 retinal vein occlusion were reported with filgotinib; there were no opportunistic infections, active tuberculosis, malignancies, gastrointestinal perforations, or deaths. Conclusions and Relevance: Among patients with active RA who had an inadequate response or intolerance to 1 or more bDMARDs, filgotinib, 100 mg daily or 200 mg daily, compared with placebo resulted in a significantly greater proportion achieving a clinical response at week 12. However, further research is needed to assess longer-term efficacy and safety. Trial Registration: ClinicalTrials.gov Identifier: NCT02873936.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Janus Quinase 1/antagonistas & inibidores , Piridinas/uso terapêutico , Triazóis/uso terapêutico , Adulto , Idoso , Antirreumáticos/efeitos adversos , Biomarcadores/sangue , Proteína C-Reativa/análise , Relação Dose-Resposta a Droga , Método Duplo-Cego , Tolerância a Medicamentos , Feminino , Testes Hematológicos , Humanos , Infecção/etiologia , Masculino , Pessoa de Meia-Idade , Piridinas/administração & dosagem , Piridinas/efeitos adversos , Indução de Remissão , Índice de Gravidade de Doença , Triazóis/administração & dosagem , Triazóis/efeitos adversos
12.
Clin Exp Rheumatol ; 37(5): 723-730, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31172920

RESUMO

OBJECTIVES: The aim of this 2-year prospective study was to assess the diagnostic and therapeutic effect of a combined gastro-rheumatological approach in enteropathic spondyloarthritis (eSpA) patients. METHODS: Inflammatory bowel disease (IBD) patients with joint pain were referred by IBD-dedicated gastroenterologists to a dedicated rheumatologist. At baseline and at 3, 6, 12, 24 months, the following parameters were recorded: clinical and biochemical variables, SpA and IBD activity scores, treatment (conventional synthetic; csDMARDs, biologics; bDMARDs). Associations between treatment and patient characteristics were evaluated by logistic regression (AOR [95% CI]). RESULTS: Overall, 229 IBD patients were referred to rheumatologists. eSpA was diagnosed in 147 (64.2%) patients: 96 (65.3%) showing peripheral and 51 (34.7%) axial involvement. IBD included Crohn's disease (CD) in 141 (61.6%) and ulcerative colitis (UC) in 88 (38.4%). bDMARD treatment increased over the follow-up (baseline-24 months: 32.7-60%; AOR 3.45 [1.93-6.2], p<0.001). bDMARD use was less frequent in elderly patients (AOR 0.73 [0.56-0.96], p=0.023), in UC (AOR 0.43 [0.2-0.94], p=0.034) and in patients with peripheral involvement (AOR 0.53 [0.3-1.04], p=0.067). csDMARD use was increased in patients with peripheral involvement (AOR 4.65 [2.09-10.33], p<0.001) and in UC (AOR 2.30 [1.13-4.67], p=0.021). CRP, ESR, ASDAS-ESR levels and BASFI significantly decreased over the follow-up, whereas the pMayo score, BASDAI and HAQ-S were unchanged. CONCLUSIONS: In this prospective study in eSpA patients, a multidisciplinary approach was shown to optimise the therapeutic management and outcome (e.g. disease activity scores). bDMARD use paralleled an improvement in disease activity scores and confirmed a good safety profile.


Assuntos
Antirreumáticos , Doenças Inflamatórias Intestinais , Espondilartrite , Idoso , Antirreumáticos/uso terapêutico , Produtos Biológicos , Colite Ulcerativa , Comorbidade , Humanos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/epidemiologia , Estudos Prospectivos , Doenças Reumáticas , Espondilartrite/tratamento farmacológico , Espondilartrite/epidemiologia
13.
Expert Opin Investig Drugs ; 28(7): 573-581, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31208237

RESUMO

Introduction: Rheumatoid arthritis (RA) is a chronic, systemic, autoimmune disease, which affects joints and extra-articular structures. Nowadays, the armamentarium of therapeutic options is progressively expanding and embraces several mechanisms of action: TNF inhibition, B-cell depletion, T-cell co-stimulation inhibition, IL-6 blockade, and JAK-inhibition. Granulocyte-Monocyte-Colony-Stimulating-Factor (GM-CSF) is a mediator acting as a cytokine with a proven pathogenetic role in RA, providing a potential alternative target for the management of the disease. Mavrilimumab is a monoclonal antibody against GM-CSF receptor, which has been successfully tested in RA patients. Areas covered: Beginning with a description of the preclinical evidence and the rationale for GM-CSF blockade in RA, this review will provide a wide overview of mavrilimumab efficacy and safety profile by analyzing phase I/II RCTs conducted in patients with moderate to severe RA. Expert opinion: According to the promising results from phase I-II RCTs, mavrilimumab could be considered as an additional therapeutic option for RA patients multi-resistant to the available targeted drugs. However, the optimal dose and the profile of this new drug should be confirmed in phase III RCTs before the marketing.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Animais , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/farmacologia , Antirreumáticos/efeitos adversos , Antirreumáticos/farmacologia , Artrite Reumatoide/fisiopatologia , Resistência a Medicamentos , Humanos , Terapia de Alvo Molecular , Receptores de Fator Estimulador das Colônias de Granulócitos e Macrófagos/antagonistas & inibidores , Índice de Gravidade de Doença
14.
Z Rheumatol ; 78(7): 660-669, 2019 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-31165251

RESUMO

BACKGROUND/OBJECTIVE: The majority of patients in Germany miss out on the necessity of early diagnosis and initiation of therapy for rheumatoid arthritis (RA) caused by considerable structural deficits in the health care system. The challenge is to reconcile the individual demand for the best possible therapy result with a sustainable expenditure of resources. METHODS: The cross-sectoral regional care network ADAPTHERA aims to improve early RA diagnosis and treatment in Rhineland-Palatinate. The retrospective triage analyses of suspected early onset RA patients was performed by tracing the selection process of all available enquiries (n = 1045). For analysis of the clinical course of the disease, a subset comprising 143 patients with a minimum observation time of 12 months (5 consecutive visits) was available. Clinical and laboratory parameters were collected quarter yearly, self-administered questionnaires were filled out and the treatment was adapted if necessary. RESULTS: A total of 454 patients were included. The mean waiting time was 23.9 (SD = 18) days. The mean observation period in the subcohort was 29.2 (SD = 12.7) months, with about 50% of the patients presenting within 3 months. Almost 75% of the patients were in remission after 2 years. A sustained remission could be described for 74.8% (6 months) and 53.5% (12 months), respectively. Especially patients with rapid remission induction benefited in terms of longer remissions (p = 0.03). A very early stage of the disease (VERA) was associated with a rarely necessary biologic therapy (p = 0.022). DISCUSSION: The approach of a supply network is not a panacea, but it might improve healthcare for patients with early onset RA. In order to minimize resource utilization, a pinpoint referral and accurate triage of potential cases are crucial.


Assuntos
Antirreumáticos , Artrite Reumatoide , Antirreumáticos/uso terapêutico , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/tratamento farmacológico , Prestação Integrada de Cuidados de Saúde , Alemanha , Humanos , Indução de Remissão , Estudos Retrospectivos , Resultado do Tratamento
15.
Z Rheumatol ; 78(5): 422-428, 2019 Jun.
Artigo em Alemão | MEDLINE | ID: mdl-31049664

RESUMO

Treat to target (T2T) strategies and comorbidities are closely related. Strong evidence exists for reducing the risk and extent of comorbidities, such as cardiovascular (CV) diseases, depression and infections by implementing T2T concepts and inducing good disease control of rheumatoid arthritis (RA) in this way. On the other hand existing comorbidities may hinder implementation of T2T concepts by aggravating RA or influencing rheumatologists to overcautiously use DMARD treatment. Among a long list of potentially relevant comorbidities with RA, in this review two particularly relevant accompanying diseases with respect to T2T, CV diseases and infections, are selected for discussion in detail. The CV comorbidities are the main cause of death for RA patients and are triggered by RA-associated inflammatory mechanisms. Their negative influence on implementation of T2T strategies can be stopped or at least reduced by optimal control of RA activity with the help of selecting drugs with cardioprotective properties (such as biologicals, methotrexate and hydroxychloroquine) as well as assessing and treating traditional CV risk factors. Infections are among most important adverse events of DMARD treatment and can disturb the optimal use of these drugs and so hinder the success of the T2T strategy. Optimal infection prophylaxis and identification of high risk patients are particularly important and minimization of glucocorticoid use is critical to reduce the risk of infections. In summary, comorbidities are important potential risk factors for the success of T2T strategies.


Assuntos
Antirreumáticos , Artrite Reumatoide , Produtos Biológicos , Doenças Cardiovasculares/epidemiologia , Infecção/epidemiologia , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/epidemiologia , Artrite Reumatoide/prevenção & controle , Produtos Biológicos/uso terapêutico , Doenças Cardiovasculares/prevenção & controle , Comorbidade , Humanos , Controle de Infecções , Metotrexato , Indução de Remissão
16.
Medicine (Baltimore) ; 98(20): e15517, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31096451

RESUMO

Access to care and management of Rheumatoid Arthritis (RA) patients may differ based on residential area. We described differences in the profile of patients initiating their first biologic disease modifying antirheumatic drug (bDMARD) based on their residential area type.Cross-sectional analysis of 793 adult RA patients in the longitudinal Ontario Best Practices Research Initiative (OBRI) registry initiating their first bDMARD <30 days prior to or anytime post-enrolment. Patient residential and clinic areas (rural vs. urban) were classified using 2 methods: postal codes and Statistics Canada population centres. Sociodemographics, disease characteristics, and RA medications (tumor necrosis factor inhibitor [TNFi] vs. non-TNFi, concurrent use of conventional synthetic DMARDs [csDMARDs], and intravenous [IV] vs. subcutaneous [SC] bDMARD) at initiation of first bDMARD were contrasted between residential area types.Other than marital status, first language, and race (higher proportion of married, English speaking, Caucasian patients in rural areas), no significant differences were observed in the demographic and disease characteristics of patients living in rural and urban areas. In multivariate analysis, there was no association between residential area type and type of bDMARD use, concurrent csDMARD(s) use or route of bDMARD. However, patients living farther from their treating clinic were significantly less likely to initiate IV bDMARD. Female rheumatologist and rural clinic location were independently associated with lower odds of IV bDMARD use.The use of SC vs. IV bDMARD was associated with being seen in a clinic located in a rural area, being treated by a female rheumatologist, and living farther from treating clinic. These results suggest possible prescription bias in bDMARD selection and/or patient preferences due to convenience.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Produtos Biológicos/uso terapêutico , Padrões de Prática Médica/estatística & dados numéricos , Características de Residência/estatística & dados numéricos , Adulto , Fatores Etários , Idoso , Antirreumáticos/administração & dosagem , Produtos Biológicos/administração & dosagem , Estudos Transversais , Vias de Administração de Medicamentos , Feminino , Acesso aos Serviços de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Ontário , População Rural/estatística & dados numéricos , Índice de Gravidade de Doença , Fatores Sexuais , Fatores Socioeconômicos , Fator de Necrose Tumoral alfa/antagonistas & inibidores , População Urbana/estatística & dados numéricos
17.
Autoimmun Rev ; 18(7): 706-713, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31059844

RESUMO

Rheumatoid Arthritis (RA) is a chronic inflammatory disease characterized by a heterogeneous clinical response to the different treatments. Some patients are difficult to treat and do not reach the treatment targets as clinical remission or low disease activity. Known negative prognostic factors, such as the presence of auto-antiantibodies and joint erosion, the presence of a genetic profile, comorbidities and extra-articular manifestations, pregnancy or a pregnancy wish may concur to the treatment failure. In this review we aimed at identify difficult to treat RA patients and define the optimal therapeutic and environmental targets. Genetic markers of severity such as HLA-DRB1, TRAF1, PSORS1C1 and microRNA 146a are differently associated with joint damage; other gene polymorphisms seem to be associated with response to biologic disease modifying anti-rheumatic drugs (bDMARDs). The presence of comorbidities and/or extra-articular manifestations may influence the therapeutic choice; overweight and obese patients are less responsive to TNF inhibitors. In this context the patient profiling can improve the clinical outcome. Targeting different pathways, molecules, and cells involved in the pathogenesis of RA may in part justify the lack response of some patients. An overview of the future therapeutic targets, including bDMARDs (inhibitors of IL-6, GM-CSF, matrix metalloproteinases, chemokines) and targeted synthetic DMARDs (filgotinib, ABT-494, pefacitinib, decernotinib), and environmental targets is addressed. Environmental factors, such as diet and cigarette smoke, may influence susceptibility to autoimmune diseases and interfere with inflammatory pathways. Mediterranean diet, low salt intake, cocoa, curcumin, and physical activity seem to show beneficial effects, however studies of dose finding, safety and efficacy in RA need to be performed.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Animais , Humanos
18.
Clin Biochem ; 69: 8-14, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31077643

RESUMO

BACKGROUND: This study aimed to evaluate the relationships between concomitant biologic disease-modifying anti-rheumatic drugs (DMARDs) and prednisolone administration and blood tacrolimus exposure or serum CYP3A4/5-related markers in rheumatoid arthritis (RA) patients without severe disease activity. METHODS: Forty-six RA patients treated with oral tacrolimus once daily for maintenance of clinical remission to moderate disease activity were enrolled. The blood concentrations of tacrolimus and its major metabolite were determined at 12 h after the evening dosing. Blood samples for determination of serum markers including 4ß-hydroxycholesterol (4ß-OHC), 25-hydroxyvitamin D (25-OHD) and interleukin-6 (IL-6), and CYP3A5 genotype were collected. RESULTS: Most enrolled patients had RA with clinical remission to mild disease activity. Concomitant tocilizumab or low-dose prednisolone administration did not alter the blood tacrolimus exposure. Serum 4ß-OHC level was lower in tocilizumab co-treated patients than in the biologic DMARD non-treated patients. The blood tacrolimus concentration was inversely correlated with the serum level of 25-OHD, but not 4ß-OHC and IL-6. The serum level of 4ß-OHC was positively associated with that of 25-OHD. No correlations were observed between the serum levels of CYP3A4/5 activity markers and IL-6. The patients with the homozygous CYP3A5*3 had the higher blood tacrolimus concentration, while CYP3A5*3 allele was not associated with the serum levels of 4ß-OHC and 25-OHD. CONCLUSIONS: Concomitant use of tocilizumab or low-dose prednisolone had no effect on the pharmacokinetics of tacrolimus, while tocilizumab lowered serum 4ß-OHC. Blood tacrolimus exposure was negatively associated with serum 25-OHD in RA patients with clinical remission to moderate disease activity.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/sangue , Artrite Reumatoide/tratamento farmacológico , Citocromo P-450 CYP3A/sangue , Imunossupressores/uso terapêutico , Prednisolona/uso terapêutico , Tacrolimo/uso terapêutico , Idoso , Antirreumáticos/administração & dosagem , Artrite Reumatoide/enzimologia , Biomarcadores/sangue , Feminino , Humanos , Hidroxicolesteróis/sangue , Imunossupressores/sangue , Limite de Detecção , Masculino , Pessoa de Meia-Idade , Prednisolona/administração & dosagem , Tacrolimo/administração & dosagem , Vitamina D/análogos & derivados , Vitamina D/sangue
19.
Drugs ; 79(8): 887-891, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31093950

RESUMO

Peficitinib [Smyraf® (Astellas Pharma)] is a Janus kinase (JAK)1, JAK2, JAK3 and tyrosine kinase (Tyk)2 (pan-JAK) inhibitor recently approved in Japan for the treatment of rheumatoid arthritis. Inhibition of JAK suppresses the activation of cytokine signalling pathways involved in inflammation and joint destruction in rheumatoid arthritis. Peficitinib has been shown to significantly improve ACR20 and other measures of disease severity and to reduce the mean modified total Sharp score change from baseline in clinical trials. This article summarizes the milestones in the development of peficitinib leading to this first approval as a treatment for rheumatoid arthritis in patients who have an inadequate response to conventional therapies.


Assuntos
Adamantano/análogos & derivados , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Niacinamida/análogos & derivados , Inibidores de Proteínas Quinases/uso terapêutico , Adamantano/farmacologia , Adamantano/uso terapêutico , Antirreumáticos/farmacologia , Aprovação de Drogas , Humanos , Janus Quinases/antagonistas & inibidores , Niacinamida/farmacologia , Niacinamida/uso terapêutico , Inibidores de Proteínas Quinases/farmacologia , Proteínas Tirosina Quinases/antagonistas & inibidores
20.
Clin Exp Rheumatol ; 37(4): 519-534, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31140394

RESUMO

The current treatment approach in rheumatoid arthritis (RA) follows a stepwise management, starting from early introduction of conventional synthetic (cs) disease-modifying anti-rheumatic drugs (DMARDs), moving to biological (b) DMARDs and targeted synthetic (ts) DMARDs. In the last few years, new drugs with different mechanisms of action have demonstrated their efficacy in treating such a disabling condition, and their approval, along with other more "experienced" treatments, has established their effectiveness on disease activity, damage accrual prevention, patients' quality of life improvement, confirming their safety profile. Moreover, new molecular pathways are under investigation as potential targets of new advanced therapies. Clinicians' capability of stratifying treatment strategies and decisions has improved, with several new tools for the optimisation of long-term management of RA; however, a high proportion of patients are refractory to the available drugs. Finally, as RA is a systemic disease, the knowledge in multi-systemic complications of the disease has grown, as well as the possibility in improving extra-articular manifestations of the disease, although certain drugs have potentially relevant non-articular effects, which need to be monitored. This narrative review summarises the most relevant studies published over the last year in the field of treatment of RA, with the major aim to let clinicians and researchers reflect on "what is new", "what is effective" and "what is safe".


Assuntos
Antirreumáticos , Artrite Reumatoide , Antirreumáticos/uso terapêutico , Quimioterapia Combinada , Humanos , Qualidade de Vida
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