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3.
An Bras Dermatol ; 99(5): 706-720, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38493053

RESUMO

Prurigo is a reactive, hyperplastic skin condition characterized by pruritic papules, plaques, and/or nodules. The temporal classification includes acute/subacute and chronic disease (≥ 6 weeks), with different clinical variants, synonymies, and underlying etiological factors. The immunology of chronic prurigo shows similarities with atopic dermatitis due to the involvement of IL-4 and IL-13, IL-22, and IL-31. Treatment includes antihistamines, topical steroids, dupilumab, and JAK inhibitors. Several conditions manifest clinically as prurigo-like lesions, and the correct clinical diagnosis must precede correct treatment. Furthermore, chronic prurigos represent a recalcitrant and distressing dermatosis, and at least 50% of these patients have atopic diathesis, the treatment of which may induce adverse effects, especially in the elderly. The quality of life is significantly compromised, and topical treatments are often unable to control symptoms and skin lesions. Systemic immunosuppressants, immunobiologicals, and JAK inhibitors, despite the cost and potential adverse effects, may be necessary to achieve clinical improvement and quality of life. This manuscript reviews the main types of prurigo, associated diseases, their immunological bases, diagnosis, and treatment.


Assuntos
Prurigo , Humanos , Prurigo/diagnóstico , Prurigo/etiologia , Prurigo/terapia , Qualidade de Vida , Doença Crônica
4.
Adv Rheumatol ; 64: 26, 2024. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1556786

RESUMO

Abstract Background To assess the drug survival and change of disease activity using a second Janus kinase inhibitor (JAKi) after failure to a JAKi and subsequent biologic disease-modifying anti-rheumatic drugs (bDMARDs) in patients with difficult-to-treat rheumatoid arthritis (RA). Methods This retrospective cohort study included 32 patients with difficult-to-treat RA who failed to a JAKi and subsequently to one or more bDMARDs and then switched to a second JAKi. To assess drug survival, electronic medical records of each patient were reviewed. Data on whether the second JAKi was discontinued, and the reasons for discontinuation were collected. The change of disease activity was assessed by analyzing changes in tender joint count (TJC), swollen joint count (SJC), patient's global assessment of disease activity on a visual-analogue scale (VAS), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), Disease Activity Score for 28 joints with ESR (DAS28-ESR), and DAS28-CRP from baseline to that at six months from initiation of the second JAKi. Results Overall, discontinuation of the second JAKi occurred in 20 (62.5%) patients. Primary failure, secondary failure, adverse events, and insurance coverage issues were the reasons for discontinuation in 9 (45.0%), 5 (25.0%), 2 (10.0%), and 4 (20.0%) patients, respectively. The estimated 2-year drug survival rate was 39.3%. In terms of change of disease activity, the second JAKi significantly improved TJC (p < 0.001), SJC (p < 0.001), VAS (p < 0.001), CRP (p = 0.026), DAS28-ESR (p < 0.001), and DAS28-CRP (p < 0.001) at 6-month compared with that at the baseline. Conclusions Second JAKi could be a therapeutic option in patients with difficult-to-treat RA who have failed to a JAKi and subsequent bDMARDs.

5.
Skin Appendage Disord ; 9(5): 380-384, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37900775

RESUMO

Introduction: Psoriasis is a chronic inflammatory disease that may also involve nails. Unfortunately, topical treatments available are limited and often responsible for side effects and/or lack of compliance due to the necessary prolonged use to see results. Intralesional treatment instead is often unwanted or unaccepted by patients. Lack of efficacy is, moreover, always a possible outcome. Novel modalities for the therapy of nail psoriasis are thus needed and always welcomed. Case Presentation: We then aimed to develop a topical 2% tofacitinib formulation expected to facilitate nail penetration and use in patients with recalcitrant forms of nail psoriasis unwilling to accept other routes of administration of treatment besides the topical one. Conclusion: These preliminary data, despite the use in 3 patients only, suggest a potential use of topical tofacitinib 2% for nail psoriasis. Further studies on bigger groups are however necessary to confirm the present encouraging results and establish the effectiveness and safety also in more severe cases or in the pediatric population.

6.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-37820832

RESUMO

INTRODUCTION: There are no studies on efficacy of tofacitinib for moderate-severe ulcerative colitis (UC) in pediatric patients in Latin America. The aim of this study was to describe the efficacy and safety, in real world, treated with tofacitinib in our setting. MATERIALS AND METHODS: Case series of pediatric patients with UC who received treatment with tofacitinib in induction phase for 8 weeks and then maintenance therapy between November 2021 and February 2023. RESULTS: Four female patients, median age 14.5 (SD 2.1; RIQ 12.5-16.5) years, all with prior biologic exposure, all 4 with prior use of anti-TNF, and 2/4 with prior use of anti-integrin. Clinical, biochemical and endoscopic remission was obtained in 3/4 at induction. Information was obtained from 3 patients in 6-month maintenance, 2/3 remained in clinical, biochemical and endoscopic remission and 1/3 has not achieved biochemical or endoscopic remission. Information was obtained from 1 patient in 12-month maintenance, achieving clinical and biochemical remission, however, endoscopic remission has not been achieved. One patient was initiated for severe acute UC with risk of colectomy, with significant improvement after 7 days, reaching therapeutic objectives at induction. No serious adverse events were reported in any of the cases. CONCLUSIONS: Efficacy and safety are demonstrated with tofacitinib in pediatric patients. With high percentage of response in induction treatment, sustained over time, and safe. In the context of severe acute hospitalized UC, it has a role as a potential rescue therapy due to its rapid action.

7.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-37806342

RESUMO

INTRODUCTION: Tofacitinib is indicated in patients with moderate to severe ulcerative colitis (UC); however, given its rapid onset of action, it may constitute an alternative in patients with hospitalized severe acute UC. There are few data on this indication in the literature. The aim of this study was to describe the efficacy and safety of tofacitinib in the management of patients with hospitalized UC, as well as its clinical characteristics and other treatment patterns. MATERIALS AND METHODS: Descriptive observational study of adults and children with CUAG treated with tofacitinib between June 2019 and December 2022 in Colombia. Sociodemographic and clinical variables were collected, therapeutic response was evaluated in different periods of time and descriptive analysis of quantitative and qualitative variables was performed. RESULTS: Six patients (five adults and one pediatric), mean age 33.2 (SD: 8.5) years, with CUAG. Symptom remission was obtained in 100% of patients at day 7 after tofacitinib initiation. In three patients information was obtained beyond 6 months, with 100% clinical, biochemical, and endoscopic remission and without requiring colectomy. In the case of the pediatric patient, symptom remission was achieved one week after starting tofacitinib, remaining in clinical, biochemical and endoscopic remission beyond 6 months. No serious adverse events were reported in any of the cases. CONCLUSIONS: Tofacitinib represents a rescue therapeutic alternative in CUAG, with rapid clinical response, adequate tolerance and less need for colectomy, being sustained for periods beyond 6 months.

8.
Rev. cuba. reumatol ; 25(2)jun. 2023.
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-1565530

RESUMO

Introducción: La dermatitis atópica es una enfermedad cutánea inflamatoria, crónica y pruriginosa. De etiología multifactorial que se produce con mayor frecuencia durante la lactancia y en la infancia temprana. Objetivos: Describir la evidencia científica sobre el efecto de los inhibidores de janus quinasa sobre la mejoría clínica y la remisión de la dermatitis atópica. Métodos: Se realizará una revisión sistemática y metaanálisis. Esta revisión sistemática se regirá de acuerdo con las directrices PRISMA. Se realizó una búsqueda en PubMed, Scopus, Web of Science. Resultados: Se incluyeron 14 artículos en la revisión. Conclusiones: El tratamiento con inhibidores del janus cinasas, como el abrocitinib, está siendo investigado como una opción potencial para el tratamiento de la dermatitis atópica y los artículos incluidos en esta revisión han demostrado resultados prometedores. El abrocitinib mostró una mejora sostenible de los síntomas de la dermatitis atópica, ha demostrado ser bien tolerado en los ensayos clínicos, con menor cantidad e intensidad de efectos secundarios, respeto a otros fármacos como cremas o corticoides sistémicos, y hasta el momento sugieren que los inhibidores de la janus cinasas son bien tolerados por la mayoría de los pacientes. Es importante destacar que el abrocitinib aún es una terapia relativamente nueva y su uso a largo plazo en el tratamiento de la dermatitis atópica requieren más investigaciones.


Introduction: Atopic dermatitis is an inflammatory, chronic, pruritic skin disease. It has a multifactorial etiology and occurs most frequently during infancy and early childhood. Aims: To describe the scientific evidence on the effect of janus kinase inhibitors on clinical improvement and remission of atopic dermatitis. Methods: A systematic review and meta-analysis will be performed. This systematic review will be conducted according to PRISMA guidelines. A search will be performed in Pubmed, Scopus, Web of Science. Results: 14 articles were included in the review. Conclusions: Treatment with janus kinase inhibitors, such as abrocitinib, is being investigated as a potential option for the treatment of atopic dermatitis and the articles included in this review have shown promising results. abrocitinib showed a sustainable improvement of atopic dermatitis symptoms, has been shown to be well tolerated in clinical trials, with fewer and less intense side effects compared to other drugs such as creams or systemic corticosteroids, and so far suggest that janus kinase inhibitors are well tolerated by most patients. Importantly, abrocitinib is still a relatively new therapy and its long-term use in the treatment of atopic dermatitis requires further investigations.

9.
An Bras Dermatol ; 98(5): 656-677, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37230920

RESUMO

The JAK-STAT signaling pathway mediates important cellular processes such as immune response, carcinogenesis, cell differentiation, division and death. Therefore, drugs that interfere with different JAK-STAT signaling patterns have potential indications for various medical conditions. The main dermatological targets of JAK-STAT pathway inhibitors are inflammatory or autoimmune diseases such as psoriasis, vitiligo, atopic dermatitis and alopecia areata; however, several dermatoses are under investigation to expand this list of indications. As JAK-STAT pathway inhibitors should gradually occupy a relevant space in dermatological prescriptions, this review presents the main available drugs, their immunological effects, and their pharmacological characteristics, related to clinical efficacy and safety, aiming to validate the best dermatological practice.


Assuntos
Dermatologia , Inibidores de Janus Quinases , Vitiligo , Humanos , Inibidores de Janus Quinases/farmacologia , Inibidores de Janus Quinases/uso terapêutico , Janus Quinases/metabolismo , Janus Quinases/farmacologia , Transdução de Sinais , Fatores de Transcrição STAT/metabolismo , Fatores de Transcrição STAT/farmacologia , Vitiligo/tratamento farmacológico
10.
Crohns Colitis 360 ; 5(1): otac050, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36777366

RESUMO

Background: Ulcerative colitis (UC) is a chronic inflammatory bowel disease which affects the colorectal mucosa with a relapsing-remitting pattern. The therapeutic options currently available for the medical management of UC include many options. Tofacitinib is an oral small molecule, Janus kinase (JAK) inhibitor, more selective for JAK1 and JAK3, which reduces the inflammatory process involved in the pathogenesis of UC. Methods: Retrospective observational multicentric study of patients with UC who used tofacitinib in any phase of their treatment. Clinical remission and response (according to Mayo score), mucosal healing, primary and secondary loss of response, discontinuation of the drug with possible causes, and the need for dose optimization or switching to biologicals, need for surgery and adverse events were evaluated. Results: From a total of 56 included patients, clinical remission was observed in 43.6% at week 12, 54.5% at week 26, 57.9% at week 52, and 40% at the last follow-up visit. Clinical response was observed in 71.4%, 81.8%, 89.5%, and 61.8% at the same time periods, respectively. Mucosal healing rates were 50% and 17.8% needed colectomy. Conclusions: Tofacitinib was effective in induction and maintenance of clinical response and remission rates, compatible to other international real-word studies and meta-analyses.

11.
Clin Rheumatol ; 42(5): 1249-1258, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36715850

RESUMO

INTRODUCTION/OBJECTIVES: Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by ongoing inflammation and degradation of synovial joints. The oral JAK inhibitor, upadacitinib, is approved for RA. We conducted an integrated safety analysis of upadacitinib 15 mg once daily (QD) in patients from Latin America (LATAM) versus the rest of the world (RoW). METHODS: Treatment-emergent adverse events (AEs) and laboratory data from six phase 3, randomized controlled trials, adjusted for upadacitinib 15 mg QD use in RA, were analyzed. RESULTS: Overall, 3209 patients received upadacitinib 15 mg QD for 7024 patient-years (PY). LATAM patients (n = 725) had a mean upadacitinib exposure of 1518 PY. Baseline characteristics were generally similar between LATAM and RoW populations. AE rates (including serious/opportunistic infections, tuberculosis, and herpes zoster) and deaths were comparable between populations. LATAM patients had lower serious AE rates per 100 PY (9.4 vs 14.0 E/100 PY) and discontinuation-related AEs (3.9 vs 6.0 E/100 PY) versus RoW. Rates of cardiovascular events were low (≤ 0.5 E/100 PY) and similar between populations. Malignancies, excluding non-melanoma skin cancer, were less common in the LATAM population versus RoW (0.2 vs 1.0 E/100 PY). Laboratory abnormalities were similar between populations, with decreases in hemoglobin, lymphocyte, and neutrophil counts, and elevations in liver enzymes and creatine phosphokinase. Mean change from baseline in low- and high-density lipoprotein cholesterol was generally comparable between LATAM and RoW populations. CONCLUSION: Upadacitinib 15 mg QD demonstrated a consistent safety profile across LATAM and RoW patient populations, with no new safety risks observed. TRIAL REGISTRATION NUMBERS: SELECT-EARLY, NCT02706873; SELECT-NEXT, NCT02675426; SELECT-COMPARE, NCT02629159; SELECT-MONOTHERAPY, NCT02706951; SELECT-BEYOND, NCT02706847; SELECT-CHOICE, NCT03086343.


Assuntos
Antirreumáticos , Artrite Reumatoide , Humanos , Antirreumáticos/efeitos adversos , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/induzido quimicamente , Compostos Heterocíclicos com 3 Anéis/efeitos adversos , América Latina , Resultado do Tratamento
12.
Gastroenterol Hepatol ; 46(7): 512-521, 2023.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-36372256

RESUMO

INTRODUCTION: There are no studies on efficacy of tofacitinib for ulcerative colitis (UC) in Latin America. The aim of this study was to describe the efficacy and safety, in the real world, of patients with moderate-severe UC treated with tofacitinib in our setting. MATERIALS AND METHODS: Multicenter descriptive observational study, in patients with UC who received treatment with tofacitinib in induction phase for 8 weeks and then, maintenance therapy, between June 2019 and June 2022. RESULTS: Thirty-four adult patients, 50% female, mean age 38.1 (range 22-72) years. 76.5% pancolitis, and 20.6% left colitis. 79.4% failure to tumor necrosis factor inhibitors (anti-TNFs), and 35.3% to vedolizumab. 14.7% naïve to biologic therapy. 23.5% had previous extraintestinal manifestations. During induction, 58.8% of patients achieved clinical, biochemical and endoscopic remission. During maintenance, 76.9% of patients at 26 weeks and 66.6% at 52 weeks presented clinical remission. Eight patients presented adverse events, none of them cardiovascular or thromboembolic. 44.1% were steroid-dependent, and 23.5% required steroids as rescue therapy. 38.3% required an increase in tofacitinib to 10mg every 12h during maintenance. In 17.6% tofacitinib was discontinued due to lack of efficacy. We included three pediatric-aged female patients, mean age 15.3 (range 14-17) years, 2/3 with pancolitis and 1/3 with left colitis, all with prior exposure to biologic therapy, who had clinical, biologic and endoscopic remission at induction. CONCLUSIONS: In this first Latin American study with tofacitinib in UC, efficacy and safety are demonstrated in the treatment of our patients with moderate to severe activity.


Assuntos
Colite Ulcerativa , Colite , Adulto , Humanos , Feminino , Criança , Idoso , Adulto Jovem , Pessoa de Meia-Idade , Adolescente , Masculino , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/induzido quimicamente , Colômbia , Piperidinas/uso terapêutico , Piperidinas/efeitos adversos , Colite/tratamento farmacológico , Resultado do Tratamento
13.
An. bras. dermatol ; An. bras. dermatol;98(5): 656-677, 2023. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1505662

RESUMO

Abstract The JAK-STAT signaling pathway mediates important cellular processes such as immune response, carcinogenesis, cell differentiation, division and death. Therefore, drugs that interfere with different JAK-STAT signaling patterns have potential indications for various medical conditions. The main dermatological targets of JAK-STAT pathway inhibitors are inflammatory or autoimmune diseases such as psoriasis, vitiligo, atopic dermatitis and alopecia areata; however, several dermatoses are under investigation to expand this list of indications. As JAK-STAT pathway inhibitors should gradually occupy a relevant space in dermatological prescriptions, this review presents the main available drugs, their immunological effects, and their pharmacological characteristics, related to clinical efficacy and safety, aiming to validate the best dermatological practice.

14.
Adv Rheumatol ; 63: 50, 2023. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1519969

RESUMO

Abstract Objective To compare the efficacy and safety between baricitinib (BARI) and tofacitinib (TOFA) for the treatment of the rheumatoid arthritis (RA) patients receiving methotrexate (MTX) in clinical practice. Methods This retrospective study recruited 179 RA patients treated with BARI (2-4 mg/d) or TOFA (10 mg/d) at The First Affiliated Hospital of Guangxi Medical University from September 2019 to January 2022. The rate of low disease activity (LDA) was used as the primary end point. Secondary end points included the Disease Activity Scale-28 (DAS-28)-C-reactive protein (CRP); the rate of DAS28-CRP remission; visual analogue scale (VAS) for pain, swollen joint, and tender joint counts; and adverse events at the 6-month follow-up. Several factors affecting LDA achievement were also analyzed. Results Seventy-four patients were treated with BARI and 105 were treated with TOFA, including 83.24% females, with a median (IQR) age of 56.0 (53.0-56.0) years old and disease duration of 12.0 (6.0-12.0) months. There was no difference of the rate of LDA between the BARI and TOFA treatment groups. All disease indices in the two groups were significantly improved, including a significantly lower VAS in the BARI group (P < 0.05), reflecting the drug efficacy after 1 and 6 months of treatment. The incidence of adverse reactions was similar in these two groups. Conclusion The treatment efficacy and safety of BARI and TOFA in the RA patients were similar, but BARI was more effective in pain relief than TOFA. An older baseline age was more likely to achieve LDA in the BARI group, while a low baseline erythrocyte sedimentation rate (ESR) was more likely to achieve LDA in the TOFA group.

15.
Rev. med. Chile ; 150(7): 849-854, jul. 2022. tab, graf
Artigo em Espanhol | LILACS | ID: biblio-1424146

RESUMO

BACKGROUND: Philadelphia negative myeloproliferative neoplasms (Ph-MPN) are clonal disorders whose pathogenesis has been elucidated in recent years, creating diagnostic and prognostic algorithms. AIM: To study JAK2, CALR y MPL gene mutations in patients with Ph-MPN. MATERIALS AND METHODS: Descriptive cross-sectional observational study of patients with MPN (2015-2019), reviewing clinical, demographic and laboratory data. JAK2, CALR and MPL gene mutations were analyzed by RT-PCR. Results: We studied 72 patients. Fifty percent had essential thrombocythemia (ET), 26.4% had polycythemia vera (PV) and 23.6% had primary myelofibrosis (PM). Bone marrow biopsy was available in 76.5%. At diagnosis, the mean age was 65.5 years and 61% were symptomatic. A thrombotic event was the most frequent problem in 20% and 25% had splenomegaly. There were statistically significant differences in hematological parameters between the different MPNs. JAK2 V617F mutation was detected in 61.1%. Only 19 JAK2 V617F negative patients were available for CALR and MPL mutation studies, identifying 10 triple negative cases. Kaplan Meier curves showed a median survival of 88 months, being similar in the three MPNs. Causes of death in 20 patients were thrombotic complications in 30%, disease progression in 25%, infection in 20%, other neoplasms in 15% and other causes in 10%. CONCLUSIONS: The presentation and frequency of JAK2 V617F, CALR and MPL mutations in our cohort was similar to those reported in other studies for ET and PM. JAK2 V617F mutation was lower for PV. No significant differences between the three MPNs were observed for overall survival. We could not assess the prognostic value of the mutations.


Assuntos
Humanos , Idoso de 80 Anos ou mais , Policitemia Vera/genética , Trombocitemia Essencial/diagnóstico , Trombocitemia Essencial/genética , Transtornos Mieloproliferativos/genética , Chile , Estudos Transversais , Hospitais Públicos , Mutação
16.
Gac Med Mex ; 158(Supl 1): 26-37, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-37734057

RESUMO

Myelofibrosis (MF) is a BCR-ABL1-negative myeloproliferative neoplasm characterized by clonal myeloproliferation, dysregulated kinase signaling, and release of abnormal cytokines. In recent years, important progress has been made in the knowledge of the molecular biology and the prognostic assessment of MF. Conventional treatment has limited impact on the patients' survival; it includes a wait-and-see approach for asymptomatic patients, erythropoiesis-stimulating agents, androgens, or immunomodulatory agents for anemia, cytoreductive drugs such as hydroxyurea for the splenomegaly and constitutional symptoms, and splenectomy or radiotherapy in selected patients. The discovery of the Janus kinase (JAK) 2 mutation triggered the development of molecular targeted therapy of MF. The JAK inhibitors are effective in both JAK2-positive and JAK2-negative MF; one of them, ruxolitinib, is the current best available therapy for MF splenomegaly and constitutional symptoms. Although ruxolitinib has changed the therapeutic scenario of MF, there is no clear indication of a disease-modifying effect. Allogeneic stem cell transplantation remains the only curative therapy of MF, but due to its associated morbidity and mortality, it is usually restricted to eligible high- and intermediate-2-risk MF patients. To improve current therapeutic results, the combination of JAK inhibitors with other agents is currently being tested, and newer drugs are being investigated.


La mielofibrosis (MF) es una neoplasia mieloproliferativa negativa para BCR-ABL1 caracterizada por mieloproliferación clonal, señalización de cinasa desregulada y liberación de citocinas anormales. En los últimos años se han realizado importantes avances en el conocimiento de la biología molecular y la valoración pronóstica de la MF. El tratamiento convencional tiene un impacto limitado en la supervivencia de los pacientes; incluye un enfoque de espera para pacientes asintomáticos, agentes estimulantes de la eritropoyesis, andrógenos o agentes inmunomoduladores para la anemia, fármacos citorreductores como la hidroxiurea para la esplenomegalia y los síntomas constitucionales, y esplenectomía o radioterapia en pacientes seleccionados. El descubrimiento de la mutación Janus cinasa (JAK) 2 desencadenó el desarrollo de la terapia dirigida molecular de la MF. Los inhibidores de JAK son efectivos tanto en MF con JAK2 positivo como con JAK2 negativo; uno de ellos, el ruxolitinib, es la mejor terapia disponible actualmente para la esplenomegalia y los síntomas constitucionales de la MF. Sin embargo, aunque el ruxolitinib ha cambiado el escenario terapéutico de la MF, no hay indicios claros de un efecto modificador de la enfermedad. El alotrasplante de células madre sigue siendo la única terapia curativa de la MF, pero debido a su morbilidad y mortalidad asociadas, generalmente se restringe a pacientes elegibles con MF de riesgo alto e intermedio 2. Para mejorar los resultados terapéuticos actuales, actualmente se está probando la combinación de inhibidores de JAK con otros agentes y se están investigando fármacos más nuevos.

17.
Gastroenterol Hepatol ; 45(7): 499-506, 2022.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-34634427

RESUMO

BACKGROUND: In the last decade, new therapies with different mechanisms of action have been approved for the treatment of moderate to severe Crohn's disease (CD) and ulcerative colitis (UC). Due to the lack of comparative head-to-head trials, the ideal positioning of agents as the most appropriate first- or second-line therapies remains to be defined. OBJECTIVE: This survey aimed to evaluate the perception and decisions of Brazilian Inflammatory Bowel Diseases (IBD) specialists in positioning of new therapies (vedolizumab [VEDO], ustekinumab [UST] and tofacitinib [TOFA]) in the management of IBD in different clinical scenarios. METHODOLOGY: An anonymous national web-based questionnaire was used to determine the positioning of treatment options in different clinical scenarios (using Google Forms platform), which involved different age ranges, phenotypes, clinical situations and previous exposure to anti-TNF agents (14 scenarios for CD and 10 scenarios for UC). In CD, physicians could choose between UST or VEDO, whilst in UC, between UST, VEDO or TOFA. Six reasons for the specific choice were proposed, such as mechanism of action, safety, method of administration or onset of action. Statistical analysis was carried out with chi-square and t-tests. RESULTS: A total of 150 out of 672 GEDIIB IBD specialists (22.32%) responded to the survey. In CD scenarios, UST was the most dominant choice (11/14 scenarios), with VEDO dominating only 3 clinical situations. In UC scenarios, VEDO was the dominant choice (8/10), with UST being chosen for scenarios that included extraintestinal manifestations. Among the reasons for specific choices, the most commonly chosen were the higher efficacy due to the intrinsic mechanism of action and safety profile. CONCLUSIONS: UST was the dominant choice as compared to VEDO in CD in most scenarios, especially due to its mechanism of action and safety. VEDO was the dominant choice as compared to UST and TOFA in UC scenarios, mainly for reasons also related to its mechanism of action and safety profile. Comparative studies including patient outcomes are needed to better define the positioning of new IBD therapeutic options in our country.


Assuntos
Colite Ulcerativa , Doença de Crohn , Doenças Inflamatórias Intestinais , Brasil , Colite Ulcerativa/tratamento farmacológico , Doença de Crohn/tratamento farmacológico , Humanos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Internet , Percepção , Inibidores do Fator de Necrose Tumoral , Ustekinumab/uso terapêutico
18.
Rev. méd. Chile ; 149(11): 1532-1538, nov. 2021. ilus, graf, tab
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-1389385

RESUMO

BACKGROUND: Philadelphia-negative myeloproliferative neoplasms (Ph-MPN) are chronic hematological disorders characterized by the overproduction of one or more mature myeloid blood cell lineages. Classical Ph-MPN are polycythemia vera (PV), essential thrombocytopenia (ET) and primary myelofibrosis (PMF). AIM: To assess the epidemiological, clinical and diagnostic characteristics of Ph-MPN in Chile. Material and Methods: Retrospective review of medical records of all patients referred as MPN from 2012 to 2017. Patients with (9;21) translocation were excluded. RESULTS: Data of 462 cases with a median age of 69 years from 10 public hospitals was reviewed. ET was the most frequently Ph-MNP found. The incidence of Ph-MPN was 1.5 x 100.000 cases. The JAK2 V617F mutation study was performed in 96% of patients and only 30% had a bone marrow biopsy. Thrombotic events were observed in 29% of patients. Bleeding events were observed in 7%. Five-year overall survival was 87%. Conclusions: ET is the most frequent Ph-MPN. The mean incidence was lower than reported in the literature, in part because of a sub diagnosis.

19.
Case Rep Dermatol ; 13(1): 190-194, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34703426

RESUMO

Vitiligo is an autoimmune skin disease presenting with areas of depigmentation. Recent reports suggest that Janus kinase (JAK) inhibitors may be an effective therapy. In this case report, we show our experience with an adolescent patient with a long history of generalized and refractory vitiligo, for which treatment with topical tofacitinib, a JAK inhibitor, associated with phototherapy for 9 months, resulted in near complete repigmentation.

20.
Rev Fac Cien Med Univ Nac Cordoba ; 78(3): 294-302, 2021 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-34617700

RESUMO

Introduction: COVID-19 morbimortality is mainly associated with development of severe acute respiratory syndrome (SARS), which has been related to an augmented immune response of the host with elevated circulating cytokines. Methods: In this prospective, multicenter, single arm (compared with a historical control), add-on, experimental phase 2 study, ruxolitinib 5 mg BID was added to standard of care in COVID-19 patients. Main objective was to determine efficacy and safety of ruxolitinib in patients with COVID-19-related SARS. Results: Even though we could not show a significant reduction of COVID-19 pneumonia patients requiring intensive care unit admission and mechanical ventilation (primary endpoint), a trend to a lower mortality rate in critical ill patients receiving ruxolitinib was reported. Administered ruxolitinib dose had to be increased according to protocol in 32% of patients, without additional toxicity. Conclusion: Side effects profile was manageable, and no direct organ injury was caused by the study drug. Ruxolitinib had a fast anti-inflammatory effect, and one-third of patients felt well immediately after starting treatment.


Introducción: La morbimortalidad por COVID-19 se asocia principalmente con el síndrome respiratorio agudo severo (SARS), relacionado con una respuesta inmunitaria aumentada del huésped con aumento de los niveles circulantes de citoquinas. Métodos: En este estudio prospectivo, multicéntrico, de un solo brazo (en comparación con un control histórico), en fase 2, se agregó ruxolitinib 5 mg dos veces al día al estándar de tratamiento en pacientes con COVID-19. El objetivo principal fue determinar la eficacia y seguridad de ruxolitinib en pacientes con SARS relacionado con COVID-19. Resultados: aunque no fue posible demostrar una reducción significativa de la proporción de pacientes con neumonía por COVID-19 que requerían ingreso en la unidad de cuidados intensivos y ventilación mecánica (criterio de valoración principal), se observó una tendencia a una menor tasa de mortalidad en los pacientes críticos que recibieron ruxolitinib. La dosis de ruxolitinib administrada tuvo que aumentarse de acuerdo con el protocolo en el 32% de los pacientes, sin toxicidad adicional. Conclusión: El perfil de efectos secundarios fue manejable y el fármaco en estudio no causó lesiones orgánicas directas. El ruxolitinib tuvo un efecto antiinflamatorio rápido y un tercio de los pacientes manifestó bienestar inmediatamente después de comenzar el tratamiento.


Assuntos
Tratamento Farmacológico da COVID-19 , Pirazóis/uso terapêutico , Humanos , Nitrilas , Estudos Prospectivos , Pirimidinas
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