Upadacitinib for psoriatic arthritis refractory to biologics : SELECT-PsA 2

Background: Upadacitinib is a Janus kinase inhibitor under evaluation for the treatment of psoriatic arthritis (PsA). We evaluated upadacitinib in patients with PsA and prior inadequate response or intolerance to at least one biologic disease-modifying antirheumatic drug (DMARD). Methods: In this 24-week randomised, placebo-controlled, double-blind, phase 3 trial, 642 patients were randomised (2:2:1:1) to once per day upadacitinib 15 mg or 30 mg, placebo followed by upadacitinib 15 mg or placebo followed by upadacitinib 30 mg at week 24. The primary endpoint was the proportion of patients achieving American College of Rheumatology (ACR) 20 response at week 12. Achievement of minimal disease activity (MDA) was assessed at week 24. Treatment-emergent adverse events are reported for all patients who received at least one dose of trial drug. Results: At week 12, significantly more patients receiving upadacitinib 15 mg and 30 mg versus placebo achieved ACR20 (56.9% and 63.8% vs 24.1%; p<0.001 for both comparisons). At week 24, MDA was achieved by more upadacitinib 15 mg-treated (25.1%) and 30 mg-treated patients (28.9%) versus placebo (2.8%; p<0.001 for both comparisons). Generally, the rates of treatment-emergent adverse events were similar with placebo and upadacitinib 15 mg and higher with upadacitinib 30 mg at week 24. Rates of serious infections were 0.5%, 0.5% and 2.8% with placebo, upadacitinib 15 mg and upadacitinib 30 mg, respectively. Conclusion: In this trial of patients with active PsA who had inadequate response or intolerance to at least one biologic DMARD, upadacitinib 15 mg and 30 mg was more effective than placebo over 24 weeks in improving signs and symptoms of PsA

Low prevalence of renal, cardiac, pulmonary, and neurological extra-articular clinical manifestations in spondyloarthritis: analysis of the Brazilian Registry of Spondyloarthritis

OBJECTIVE: To describe the extra-articular manifestations (cardiac, renal, pulmonary, and neurological), usually not related to spondyloarthritis (SpA), in a large cohort of Brazilian patients. MATERIALS AND METHODS: This retrospective study analyzed 1,472 patients diagnosed with SpA and cared for at 29 health care centers distributed in the five major geographic regions in the country, participating in the Brazilian Registry of Spondyloarthritis (BRS). All patients were assessed for the prevalence of major extra-articular manifestations (cardiac, renal, pulmonary, and neurological), classified according to the diagnosis [ankylosing spondylitis (AS), psoriatic arthritis (PsA), reactive arthritis (ReA), arthritis associated with inflammatory bowel disease (IBD), undifferentiated spondyloarthritis (uSpA), and juvenile SpA], and according to the clinical presentation (axial, peripheral, mixed, and enthesitis). RESULTS: Of the patients with SpA assessed, 963 had AS, 271 PsA, 49 ReA, 48 arthritis associated with IBD, 98 uSpA, and 43 juvenile SpA. Cardiac involvement was reported in 44 patients (3.0%), pulmonary involvement in 19 (1.3%), renal involvement in 17 (1.2%), and neurological involvement in 13 patients (0.9%). Most patients with visceral involvement had AS or PsA, and the mixed (axial + peripheral) and/or predominantly axial clinical form. CONCLUSION: Cardiac, renal, pulmonary, and neurological extra-articular manifestations are quite infrequent in SpA, ranging from 0.9% to 3% in this large Brazilian cohort, and affected predominantly patients with AS and PsA.OBJETIVO: Descrever as manifestações extra-articulares (cardíacas, renais, pulmonares e neurológicas) geralmente não relacionadas às espondiloartrites (EpA) em uma grande coorte de pacientes brasileiros. MÉTODOS: Este estudo retrospectivo analisou 1.472 pacientes com o diagnóstico de EpA atendidos em 29 centros distribuídos pelas cinco principais regiões geográficas do Brasil, integrantes do Registro Brasileiro de Espondiloartrites. Todos os pacientes foram avaliados para a prevalência das principais manifestações extra-articulares (cardíacas, renais, pulmonares e neurológicas), divididas por diagnóstico [espondilite anquilosante (EA), artrite psoriásica (AP), artrite reativa (ARe), artrite associada a doença inflamatória intestinal (DII), EpA indiferenciada (EI) e EpA juvenil] e por forma clínica (axial, periférica, mista e entesítica). RESULTADOS: Dentre os pacientes avaliados com EpA, 963 apresentavam EA, 271 AP, 49 ARe, 48 artrite associada a DII, 98 EI e 43 EpA juvenil. Acometimento cardíaco foi observado em 44 pacientes (3,0%), seguido por acometimento pulmonar em 19 (1,3%), renal em 17 (1,2%) e neurológico em 13 pacientes (0,9%). A maioria dos casos de acometimento visceral ocorreu nos pacientes com EA ou AP e naqueles com forma clínica mista (axial e periférica) e/ou predominantemente axial. CONCLUSÃO: As manifestações extra-articulares cardíacas, renais, pulmonares e neurológicas são muito pouco frequentes nas EpA, variando de 0,9%-3% nesta grande coorte brasileira, estando mais associadas a EA e AP.37938

Quality of life in spondyloarthritis : analysis of a large Brazilian cohort

Objetivo: analisar as variáveis demográficas e clínicas associadas à diminuição da qualidade de vida em uma grande coorte brasileira de pacientes com espondiloartrite (EpA). Métodos: Foi aplicado um protocolo de pesquisa único a 1.465 pacientes brasileiros classificados como tendo EpA de acordo com os critérios do European Spondyloarthropaties Study Group (ESSG), atendidos em 29 centros de referência em reumatologia do Brasil. Foram registradas as variáveis clínicas e demográficas. A qualidade de vida foi analisada por meio do questionário Ankylosing Spondylitis Quality of Life (ASQoL). Resultados: A pontuação média do ASQoL foi de 7,74 (+ 5,39). Ao analisar doenças específicas no grupo de EpA, as pontuações do ASQoL não apresentaram diferença estatisticamente significativa. Os dados demográficos mostraram piores escores de ASQoL associados ao gênero feminino (p = 0,014) e etnia negra (p < 0,001). Quanto aos sintomas clínicos, a dor na região glútea (p = 0,032), a dor cervical (p < 0,001) e a dor no quadril (p = 0,001), estiveram estatisticamente associadas a piores escores no ASQoL. O uso contínuo de fármacos anti-inflamatórios não esteroides (p < 0,001) e agentes biológicos (p = 0,044) esteve associado a escores mais elevados de ASQoL, enquanto outros medicamentos não interferiram nos escores do ASQoL. Conclusão: Nesta grande série de pacientes com EpA, o sexo feminino e a etnia negra, bem como sintomas predominantemente axiais, estiveram associados a uma qualidade de vida reduzida.Objective: to analyze quality of life and demographic and clinical variables associated to its impairment in a large Brazilian cohort of patients with spondyloarthritis (SpA). Methods: A common protocol of investigation was applied to 1465 Brazilian patients classified as SpA according to the European Spondyloarthropaties Study Group (ESSG) criteria, attended at 29 reference centers for Rheumatology in Brazil. Clinical and demographic variables were recorded. Quality of life was analyzed through the Ankylosing Spondylitis Quality of Life (ASQoL) questionnaire. Results: The mean ASQoL score was 7.74 (± 5.39). When analyzing the specific diseases in the SpA group, the ASQoL scores did not present statistical significance. Demographic data showed worse scores of ASQoL associated with female gender (p = 0.014) and African-Brazilian ethnicity (p < 0.001). Regarding clinical symptoms, buttock pain (p = 0.032), cervical pain (p < 0.001) and hip pain (p = 0.001), were statistically associated with worse scores of ASQoL. Continuous use of nonsteroidal anti-inflammatory drugs (p < 0.001) and biologic agents (p = 0.044) were associated with higher scores of ASQoL, while the other medications did not interfere with the ASQoL scores. Conclusion: In this large series of patients with SpA, female gender and African-Brazilian ethnicity, as well as predominant axial symptoms, were associated with impaired quality of life

Efficacy And Tolerability Of Unsaponifiables Of Avocado And Soy In The Treatment Of Symptomatic Hip And Knee Osteoarthritis [eficácia Sintomática Dos Insaponificáveis De Abacate E Soja (ias) No Tratamento De Osteoartrose (oa) De Quadril E Joelho]

Background: Osteoarthritis (OA) is an idiopathic, multifatorial disease characterized by a progressive and slow loss of articular cartilage. Objectives: To evaluate efficacy and tolerability of unsaponifiables of avocado and soy in the treatment of symptomatic hip and knee OA. Methods: Two hundred and thirty one patients of both sexes were included, aged 45 to 75 years old, that presented hip and/ or knee symptomatic OA. They entered an open label, non-randomized, controlled trial for 6 months. They followed a 15 days washout period for anti-inflammatory drugs (NAIDs). Efficacy was evaluated according to: 1) Lequesne Algo-Funcional Index (IFL) e 2) pain in the Visual Analogue Scale (VAS; 100 mm), NAIDs/analgesics ingestion and total incapacity score (EVA de 100 mm). Results: Two hundred and thirty one patients received IAS. The data for all patients were available in the final evaluation (6 months). The average +/- SEM in the LFI improved from 11,88+/-0,24 to 6,84+/-0,29 in the final evaluation-6 months (p < 0,001). Pain improved from 6,65+/-0,11 mm to 3,21+/-0,17 mm (p= 0,001). NAIDs consumption improved from 1,95+/-0,10 to 0,67+/-0,14 (p <0,001). Success rate was 42,3% in the IAS after 6 months. Tolerance was considered good or excellent. Conclusion: The ASU in this open label controlled multicentric study shown to be effective and safe for the symptomatic pain of AO of the hip and knee. Long term studies are needed to determine the possible mechanisms of action.6111711718Mauviel, A., Daireaux, M., Hartman, Dj., Galera, P., Loyan, G., Pujol, J.P., Effects des insaponifables d'avocat et de soja (PIAS) sur la production de collagene par des cultures des synoviocytes, chondrocytes articularis et fibroblasts dermiques (1989) Rev Rhum Mal Osteoartic, 56, pp. 307-311Mauviel, A., Loyan, G., Pujol, J.P., Effect des insaponifiables d'avocat et soja (Piascledine) sur l'activité collagénolytique des cultures de synoviocytes articulaires de lapin traits par l'interleukine-1 (1991) Rev. Rhum Osteoartic., 58, pp. 241-245Henrotin, Y., Labase, A., Zheng, S.X., De Groote, D., Jaspar, J.-M., Guillon, B., Effects of three avocato/soybean mixtures of metaloproteinases, cytokines, and prostaglandin E 2 production by human articular chondrocytes metabolism (1998) Clin Rheumatol, 17, pp. 31-39Boumediène, R., Bobdanowicz, P., Felisaz, N., Galera, P., Pujol, J.P., Avocado/soya unsaponiftables enhance expression of transforming growth factor β-1 and plasminogen activation inhibitor-1 in cultured articular chondrocytes (1999) Arthritis & Rheumatism, 42, pp. 148-156Mazièzes, B., Tempesta, C., Tiechard, M., Vaguier, G., Pathologic and biochemical effects of a lipidic avocado and soya extract on an environmental post-contusive model of OA (1993) Osteoarthritis Cartilage, 1, p. 46Blotman, F., Maheu, E., Wulwik, A., Caspard, H., Lopez, A., Efficacité et tolerance des insaponifiables d'avocat/soja dans le traitement de la gonarthrose et de la coxarthrose symptomatiques. Essai prospectif, multicentrique, de trois mois, randomize, en double insu, controlê versus placebo (1997) Revue du Rhumatisme - Edition Francaise, 64 (12), pp. 944-954Altman, R., Asch, E., Bloch, D., Bole, G., Borenstein, D., Brandt, K., Development of criteria for the classification and reporting of osteoarthritis: Classification off osteoarthritis of the knee (1986) Arthritis Rheum., 29, pp. 1039-1049Altman, R., Alarcón, G., Applerouth, D., Bloch, D., Borenstein, D., Brandt, K., The American College of Rheumatology criteria for the classification and reporting of osteoarthritis of the hip (1991) Arthritis Rheum., 34, pp. 505-514Lequesne, M., Méry, C., Samson, M., Gerard, P., Indexes of severity for the osteoarthritis of the hip and the knee (1987) Scand J Rhematol, 65 (SUPPL.), pp. 85-89Maheu, E., Mazieres, B., Valat, J.-P., Loyau, G., Le Loet, X., Burgeois, P., Grouin, J.-M., Rozenberg, S., Symptomatic efficacy or avocado/soybean unsaponifiables in the treatment of the knee and hip. A prospective, randomized, double-blind, placebo controlled, multicenter clinic trial with six month treatment period and a two-month follow-up demonstrating a persistent effect (1998) Arthritis Rheum, 41, pp. 81-91Appleboom, T., Schuermans, J., Verbruggen, G., Henrotin, Y., Reginster, J.Y., Symptoms modifying effect of avocado/soybean unsaponifiables (ASU) in knee osteoarthritis (2001) Scand J Rheumatol, 30, pp. 242-247Lequesne, M., Brandt, K., Bellamy, N., Moskowitz, R., Menkes, C.J., Pelletier, J.P., Guidelines for testing slow acting drugs in osteoarthritis (1994) J Rheumatol, 21 (41 SUPPL.), pp. 65-71Altman, R., Brandt, K., Hochberg, M., Moskowitz, R., Bellamy, N., Block, D.A., Design and conduct of clinical trials in patients with osteoartriritis: Recommendations from a task force of the Osteoarthritis Research Society. Results of a workshop (1996) Osteoarthritis Cartilage, 4, pp. 217-43