A double-blind, placebo-controlled, multi-crossover trial of treatment with a chemokine antagonist for knee osteoarthritis pain
Edwards, Robert R; Tarpey, Thaddeus; Ashburn, Michael; Baer, Caitlin; Campbell, Allison; Dworkin, Robert H; Gaspard, Gabrielle; Flynn, Martina; Hade, Erinn; Jain, Nitin; Judge, Heidi; Kamp, Cornelia; Li, Yi; Meropol, Sharon; Petkova, Eva; Philip, Annie; Przkora, Rene; Rathmell, James P; Robinson-Papp, Jessica; Samuels, Jonathan; Sehgal, Nalini; Sienty, Jackie; Stacey, Brett; Wallace, Mark; Wasan, Ajay D; Wise, Barton; Yu, Chang; Fava, Maurizio; Troxel, Andrea B
Osteoarthritis, especially knee osteoarthritis, is a leading cause of disability and reduced quality of life. The etiology of pain in osteoarthritis is multifactorial, and one promising potential treatment approach involves targeting chemokine systems. The present study was a phase 2, multisite, multiperiod randomized crossover trial of CNTX-6970, a small molecule and selective oral cytokine chemokine receptor type 2 (CCR2) and CCR5 antagonist, in patients with painful knee osteoarthritis (OA). It represents the first trial performed within the National Institutes of Health's Early Phase Pain Investigation Clinical Network. The primary objectives were to evaluate the safety and efficacy of CNTX-6970, relative to placebo, for the treatment of moderate to severe pain related to knee OA. A total of 55 participants were randomized in this multiperiod crossover trial. Linear mixed effects models revealed no significant pain-related benefits of active medication; indeed, trial participants reported slightly higher knee pain intensity when taking the novel chemokine antagonist CNTX-6970 than when taking placebo. In addition, biomarker analysis revealed notably higher level of serum monocyte chemoattractant protein 1 levels when patients were on CNTX-6970 compared to placebo. Overall, although CNTX-6970 was safe and relatively well-tolerated, pharmacologic blockade of specific chemokine receptors with this compound was not effective in reducing moderate-to-severe knee osteoarthritis pain.
PMID: 41468282
ISSN: 1872-6623
CID: 6001132
The International Guideline for the Definition, Classification, Diagnosis and Management of Urticaria
Zuberbier, T; Abdul Hameed Ansari, Z; Abdul Latiff, A H; Abuzakouk, M M; Agcaoili-De Jesus, M S; Agondi, R C; Al-Ahmad, M; Alangari, A A; Alhameli, H; Alonso Bello, C D; Alshareef, S; Al-Tamemi, S; Altrichter, S; Al Wahshi, H; Aquilina, S; Araújo, M; Arnaout, R; Asero, R; Ballmer-Weber, B; Bangert, C; Bauer, A; Ben-Shoshan, M; Bernstein, J; Bindslev-Jensen, C; Bizjak, M; Boccon-Gibod, I; Bonnekoh, H; Bouillet, L; Brockow, K; Brzoza, Z; Bulatović Ćalasan, M; Bulkhi, A; Buttgereit, T; Bygum, A; Caballero, T; Calderon, O; Campos, R; Cancian, M; Carne, E; Castor, M A; Cerecedo, I; Çetinarslan, T; Cherrez-Ojeda, I; Chkhikvadze, N; Chong-Neto, H J; Choo, K; Christoff, G; Chu, C-Y; Ciupka, K; Conlon, N; Costa, C; Craig, T; Criado, P; Danilycheva, I; Darlenski, R; De Arruda Chaves, E; de Montjoye, L; Doutre, M S; Du-Thanh, A; Ebo, D; Elkhalifa, S; Elmariah, S; El-Shanawany, T; Ensina, L F; Ertaş, R; Fachini Jardim Criado, R; Ferrer, M; Ferrucci, S; Fok, J S; Fomina, D; Fonacier, L; Fouda, G; Francescantonio, I; Fukunaga, A; Galvan Calle, C A; Garcia, E; Gáspár, K; Gelincik, A; Geng, S; Godse, K; Gonçalo, M; Gotua, M; Grattan, C; Grosber, M; Guidos Fogelbach, G; Guilarte, M; Guillod, R; Hamelmann, E; Hawkes, J; Hayama, K; Heuer, R; Hide, M; Hoetzenecker, W; Inomata, N; Kang, H-R; Kaplan, A; Kapp, A; Karam, M; Kasperska-Zajac, A; Katelaris, C H; Kessel, A; Khoshkhui, M; Kim, B; Kinaciyan, T; Kocatürk, E; Kolacinska-Flont, M; Kolkhir, P; Konstantinou, G N; Kosnik, M; Krasowska, D; Kulthanan, K; Kumaran, M S; Kuprys-Lipinska, I; Labrador, M; Larco, J I; Larenas-Linnemann, D; Latysheva, E; Lazaridou, E; Li, P H; Lima, H; Lippert, U; Magerl, M; Makris, M; Alves Marcelino, J; Marzano, A V; Medina, I; Meshkova, R; Micallef, D; Mohammed Ali, R; Mortz, C G; Munoz, M; Oude Elberink, H N G; Nakonechna, A; Nasr, I; Nast, A; Netchiporouk, E; Nettis, E; Nieto, S; Ogueta Canales, I; Okas, T-L; Orfali, R L; Özkaya, E; Parisi, C; Pennitz, A; Pawankar, R; Pereira, M P; Peter, J; Petkova, E; Pigatto, P D; Podder, I; Popov, T; Porebski, G; Pyatilova, P; Ramon, G D; Ratti Sisa, H A; Recto, M; Ress, K; Ridge, K; Riedl, M; Ritchie, C; Rosario Filho, N; Rosmaninho, I; Rudenko, M; Rukhadze, M; Rutkowski, K; Sabato, V; Sahiner, U M; Saini, S; Saleh Al Sabbagh, F; Salman, A; Salvo, F; Sanchez, J; Santucci, A; Schliemann, S; Schmid-Grendelmeier, P; Sekerel, B E; Serpa, F; Sheikh, F; Sheikh, J; Shendi, H; Siebenhaar, F; Sonomjamts, M; Soria, A; Sousa Pinto, B; Staevska, M; Staubach, P; Stephan, M; Stevanovic, K; Stingeni, L; Stobiecki, M; Su Küçük, Ö; Sussman, G; Szegedi, A; Takahagi, S; Tanaka, A; Teovska Mitrevska, N; Thomsen, S F; Toubi, E; Tsatsou, F; Turk, M; Vadasz, Z; Valerieva, A; Valle, S; Doorn, M V; Veleiro Perez, B; Vera Ayala, C E; Vestergaard, C; Vieira, R J; Maruta, C W; Wedi, B; Werner, R N; Yap, E W Y; Xepapadaki, P; Xiang, Y; Ye, Y-M; Yong, P; Yosipovitch, G; Zalewska-Janowska, A Z J; Zeyen, C; Zhao, Z; Metz, M; Giménez-Arnau, A M
This update and revision of the international guideline for urticaria was developed in accordance with the methods recommended by Cochrane and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) working group. It is an initiative of the Global Allergy and Asthma Excellence Network (GA2LEN) and its Urticaria and Angioedema Centers of Reference and Excellence (UCAREs and ACAREs), with the participation of 210 delegates from 107 national and international societies, from 59 countries. The consensus conference was held on December 6th, 2024. This guideline was acknowledged and accepted by the European Union of Medical Specialists (UEMS). Urticaria is a frequent, mast cell-driven disease, defined by a rapid appearance of wheals, angioedema, or both. The lifetime prevalence of acute urticaria is estimated to be approximately 20%. Chronic urticaria, categorized as either chronic spontaneous urticaria or chronic inducible urticaria, is disabling, impairs quality of life, and affects performance at work and school, however, novel therapies are available. This updated version of the international guideline for urticaria covers the definition and classification of urticaria and outlines expert-guided and evidence-based diagnostic and therapeutic approaches for the different subtypes of urticaria.
PMID: 41649409
ISSN: 1398-9995
CID: 6000592