Recommendations of the Brazilian Society of Rheumatology for the use of JAK inhibitors in the management of rheumatoid arthritisAdvances in Rheumatology - Tập 61 - Trang 1-13 - 2021
Karina Rossi Bonfiglioli, Licia Maria Henrique da Mota, Ana Cristina de Medeiros Ribeiro, Adriana Maria Kakehasi, Ieda Maria Magalhães Laurindo, Rina Dalva Neubarth Giorgi, Angela Luzia Branco Pinto Duarte, Ana Paula Monteiro Gomides Reis, Mariana Peixoto Guimarães Ubirajara e Silva de Souza, Claiton Viegas Brenol, Geraldo da Rocha Castelar Pinheiro, Cleandro Pires de Albuquerque, Charlles Heldan de Moura Castro, Gustavo Luiz Behrens Pinto, Jose Fernando Verztman, Luciana Feitosa Muniz, Manoel Barros Bertolo, Maria Raquel da Costa Pinto, Paulo Louzada Júnior, Vitor Alves Cruz, Ivanio Alves Pereira, Max Vitor Carioca de Freitas, Bóris Afonso Cruz, Eduardo Paiva, Odirlei Monticielo, José Roberto Provenza, Ricardo Machado Xavier
Rheumatoid arthritis (RA) is a chronic and autoimmune systemic inflammatory disease that can cause irreversible joint deformities, with increased morbidity and mortality and a significant impact on the quality of life of the affected individual. The main objective of RA treatment is to achieve sustained clinical remission or low disease activity. However, up to 40% of patients do not respond to available treatments, including bDMARDs. New therapeutic targets for RA are emerging, such as Janus kinases (JAKs). These are essential for intracellular signaling (via JAK-STAT) in response to many cytokines involved in RA immunopathogenesis. JAK inhibitors (JAKi) have established themselves as a highly effective treatment, gaining increasing space in the therapeutic arsenal for the treatment of RA. The current recommendations aim to present a review of the main aspects related to the efficacy and safety of JAKis in RA patients, and to update the recommendations and treatment algorithm proposed by the Brazilian Society of Rheumatology in 2017.
Quadriceps muscle properties in rheumatoid arthritis: insights about muscle morphology, activation and functional capacityAdvances in Rheumatology - Tập 60 - Trang 1-9 - 2020
Denise Blum, Rodrigo Rodrigues, Jeam Marcel Geremia, Claiton Viegas Brenol, Marco Aurélio Vaz, Ricardo Machado Xavier
Rheumatoid arthritis (RA) is an inflammatory and chronic autoimmune disease that leads to muscle mass loss and functional capacity impairment, potentiated by physical inactivity. Despite evidences demonstrate neuromuscular impairments in RA patients, aging effects may have masked the results of similar previous studies. The aim of study was to verify (i) the effects of RA on functional capacity and muscle properties in middle-aged patients and (ii) the association between age, clinical characteristics, quadriceps muscle properties and functional capacity. Thirty-five RA women and 35 healthy age-matched women were compared with the following outcomes: (i) physical activity level through the International Physical Activity Questionnaire (IPAQ); (ii) timed-up and go (TUG) test; (iii) isometric knee extensor muscular strength; and (iv) vastus lateralis muscle activation and muscle architecture (muscle thickness, pennation angle and fascicle length) during an isometric test. An independent Student t-test and partial correlation (controlled by physical activity levels) were performed, with p < 0.05. Compared with healthy women, RA presented (i) lower physical activity level (− 29.4%; p < 0.001); (ii) lower isometric knee extensor strength (− 20.5%; p < 0.001); (iii) lower TUG performance (− 21.7%; p < 0.001); (iv) smaller muscle thickness (− 23.3%; p < 0.001) and pennation angle (− 14.1%; p = 0.011). No differences were observed in muscle activation and fascicle length. Finally, the correlation demonstrated that, with exception of TUG, muscle strength and muscle morphology were not associated with age in RA, differently from healthy participants. Middle-aged RA patients’ impairments occurred due to the disease independently of the aging process, except for functional capacity. Physical inactivity may have potentiated these losses.
Drug survival and change of disease activity using a second janus kinase inhibitor in patients with difficult-to-treat rheumatoid arthritis who failed to a janus kinase inhibitor and subsequent biologicsAdvances in Rheumatology - Tập 64 Số 1
Oh Chan Kwon, Won‐Ho Choi, Soo Min Ahn, Ji Seon Oh, Seokchan Hong, Chang‐Keun Lee, Bin Yoo, Min-Chan Park, Yong‐Gil Kim
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.
Fibronectin extra domain A as a drug delivery targeting epitope for rheumatoid arthritisAdvances in Rheumatology - - 2022
Victor Sun, Terry Melim, Soumya Mitra, Jon W. Erickson, Shaughn Bryant, Avery Farnham, Susan V. Westmoreland, Heather Knight, Liang Zhang, Wendy Ritacco, Kristoff T. Homan, Lorenzo Benatuil, Annette J. Schwartz Sterman, Andrew Goodearl
Abstract
Objectives
To assess the ability of monoclonal antibodies (mAbs) specific for fibronectin extra-domain A (FnEDA) to target diseased tissues of mouse collagen induced arthritis (mCIA) models. To explore the parameters of the targeting exhibited by anti-FnEDA mAbs including timing and location.
Methods
Targeting capabilities of anti-FnEDA mAbs were demonstrated by biodistribution study where i.v. injected antibodies were detected by conjugated near-infrared (NIR) fluorophore, 125I label and immunohistochemistry (IHC) of the injected antibody. Location of FnEDA expression in both mCIA and human RA tissue were mapped by IHC. Quantification of anti-FnEDA mAbs targeted to disease tissue was measured by whole-body autoradiography (WBA). Timing of the targeting was interrogated with fluorescent and confocal microscopy using anti-FnEDA mAbs labeled with different fluorophores and injected at different times.
Results
Anti-FnEDA mAbs show specific targeting to diseased paws of mCIA animal. The targeting was focused on inflamed synovium which is consistent with FnEDA expression profile in both mCIA and human RA tissues. Anti-FnEDA mAbs accumulated in diseased tissue at pharmacologically relevant concentrations, the targeting was sustained for up to 14 days and FnEDA was able to support targeting of multiple doses of anti-FnEDA mAbs given 5 days apart.
Conclusion
FnEDA is specifically upregulated in the inflamed tissues of mCIA. Antibodies specific for FnEDA can be useful as molecular delivery vehicles for disease specific targeting of payloads to inflamed joint tissue.
Lung involvement prevalence in patients with early rheumatoid arthritis without known pulmonary disease: a multicentric cross sectional studyAdvances in Rheumatology - Tập 61 - Trang 1-7 - 2021
Francisco Paulin, Anastasia Secco, Federico Benavidez, Juan José Rodríguez Moncalvo, Orlando Gabriel Carballo, Fernanda Ingenito, Martin Eduardo Fernández, Agustina Cáceres, Fabian Caro, Patricia Sasaki, María Laura Alberti, Paola Orausclio, Augusto Riopedre, Santiago Rossi, María Celina de la Vega
Clinically evident interstitial lung disease (ILD) affects between 10 and 42% of the patients with rheumatoid arthritis (RA). Airway involvement seems to be even more common. Most of the available evidence comes from studies performed in established RA patients. The aim of our study was to know the prevalence of non-diagnosed lung disease (airway and interstitial involvement) in patients with early RA and look for associated factors. We designed an observational, multicenter, cross-sectional study, and included patients with RA of less than two years since diagnosis. We performed a structured questionnaire, HRCT and lung functional tests looking for lung disease, together with joint disease evaluation. We analyzed which variables were associated with the presence of lung disease on HRCT. We included 83 patients, 83% females. The median (IQR) of time since RA diagnosis was 3 (1–6) months. In the HRCT, 57 patients had airway compromisea (72%), and 6 had interstitial abnormalities (7.5%). The most common altertion found in lung functional tests was a reduced DLCO (14%). The presence of at least one abnormality in the physical exam was associated with lung involvement on HRCT [13 (21.6%) vs 0 (0%); p = 0.026]. Also, patients with lung involvement presented significantly lower values of FVC% and DLCO%, and higher values of RV/TLC. No variable related to joint involvement was found associated with alterations in HRCT. Our study shows that a large proportion of early RA patients has abnormal findings in HRCT. Further studies are required to confirm these findings.
Clinical and pathophysiologic relevance of autoantibodies in rheumatoid arthritisAdvances in Rheumatology - Tập 59 - Trang 1-13 - 2019
Sara de Brito Rocha, Danielle Cristiane Baldo, Luis Eduardo Coelho Andrade
Rheumatoid arthritis (RA) is an autoimmune/inflammatory disease affecting 0.5 to 1% of adults worldwide and frequently leads to joint destruction and disability. Early diagnosis and early and effective therapy may prevent joint damage and lead to better long-term results. Therefore, reliable biomarkers and outcome measures are needed. Refinement of the understanding of molecular pathways involved in disease pathogenesis have been achieved by combining knowledge on RA-associated genes, environmental factors and the presence of serological elements. The presence of autoantibodies is a distinctive feature of RA. Rheumatoid Factor and Anti-Citrullinated Protein Antibodies are the two most remarkable autoantibodies in RA and provide different clinical and pathophysiological information. They precede the onset of disease symptoms and predict a more severe disease course, indicating a pathogenetic role in RA. Therefore, they promote a more accurate prognosis and contribute for a better disease management. Several RA-associated autoantibody systems have been identified: Anti-Carbamylated Antibodies, Anti-BRAF, Anti-Acetylated, Anti-PAD4 antibodies and others. Hopefully, the characterization of a comprehensive array of novel autoantibody systems in RA will provide unique pathogenic insights of relevance for the development of diagnostic and prognostic approaches compatible with an effective personalized medicine.
2017 recommendations of the Brazilian Society of Rheumatology for the pharmacological treatment of rheumatoid arthritisAdvances in Rheumatology - - 2018
Lícia Maria Henrique da Mota, Adriana Maria Kakehasi, Ana Paula Monteiro Gomides, Ângela Luzia Branco Pinto Duarte, Bóris Afonso Cruz, Claiton Viegas Brenol, Cleandro Pires de Albuquerque, Geraldo da Rocha Castelar Pinheiro, Iêda Maria Magalhães Laurindo, Ivânio Alves Pereira, Manoel Barros Bértolo, Mariana Peixoto Guimarães Ubirajara Silva de Souza, Marcos Rabelo de Freitas, Paulo Louzada‐Júnior, Ricardo Machado Xavier, Rina Dalva Neubarth Giorgi
The effects of cultural background on patient-perceived impact of psoriatic arthritis - a qualitative study conducted in Brazil and FranceAdvances in Rheumatology - Tập 58 - Trang 1-9 - 2018
Penélope Esther Palominos, Laure Gossec, Sarah Kreis, César Luis Hinckel, Rafael Mendonça da Silva Chakr, Ana Laura Didonet Moro, Willemina Campbell, Maarten de Wit, Niti Goel, Charles Lubianca Kohem, Ricardo Machado Xavier
In psoriatic arthritis (PsA) almost all qualitative studies have been performed in European populations. This work aimed to evaluate the impact of PsA in Brazilian and French subjects, as well as to explore cultural differences in the experience of disease and to recognize domains important for patients living with PsA outside Europe. A qualitative study was conducted in two university hospitals in Brazil and France; outpatients fulfilling Classification Criteria for PsA participated in individual interviews regarding the impact of PsA; interviews were conducted in the local language. The sample size was defined by saturation; interviews were recorded and transcribed and content analysis was performed. Fifteen patients were interviewed in Brazil and 13 in France. Mean disease duration was 16.5 ± 12.5 years (range: 8 months to 47 years) and 14.4 ± 8.4 years (range 12 months to 29 years) for Brazilian and French subjects, respectively. A broad impact was perceived: 67 codes emerged from the interviews and were grouped in 41 categories. Although 2/3 of categories were common to both nationalities, some important health domains from the perspective of PsA patients from a non-European background were brought to light including sexual dysfunction, emotional impact of psoriasis and impact of prejudice on social and professional life. This study highlights the importance of assessing the impact of PsA on a national level, emphasizing the common cross-cultural aspects but also revealing domains of interest for patients with PsA living outside Europe which merit further study.
Within and between-days repeatability and variability of plantar pressure measurement during walking in children, adults and older adultsAdvances in Rheumatology - Tập 58 - Trang 1-7 - 2018
Pedro S. Franco, Cristiane F. Moro, Mariane M. Figueiredo, Renato R. Azevedo, Fernando G. Ceccon, Felipe P. Carpes
Previous studies discussed the repeatability and variability in plantar pressure measurement, but a few considered different age groups. Here we determine within and between-days repeatability and variability of plantar pressure measurement during gait in participants from different age groups. Plantar pressure was recorded in children, young adults and older adults walking at preferred speed in four non-consecutive days within one week. Data from 10 steps from each foot in each day were analyzed considering the different regions of the foot. Mean and peak plantar pressure and data variability were compared between the steps, foot regions and days. To describe mean and peak pressure during gait in children and adults a single measurement can be enough, but elderly will requires more attention especially concerning peak values. Variability in mean pressure did not differ between age groups, but peak pressure variability differed across foot regions and age groups. One single observation can be used to describe plantar pressure during gait in children and adults. When the interest concerns older people, it might be pertinent to consider more than one day of assessment, especially when looking at peak pressure.
