Asma. Los monoclonales que vienen
Resumen
Los nuevos tratamientos biológicos, actúan sobre vías patogénicas muy específicas, y por lo tanto cada vez va a ser más importante determinar el perfil individual de alteraciones fisiopatológicas predominante en cada paciente para prescribir el tratamiento más adecuado en cada caso. El tratamiento del asma grave alérgica con un anticuerpo monoclonal anti-IgE (omalizumab) ha mostrado ser eficaz en un número elevado de pacientes, y nuevos anticuerpos anti-IgE con mejores propiedades farmacodinámicas están siendo investigados.
Entre las terapias en desarrollo, los medicamentos biológicos dirigidos a bloquear ciertas citoquinas proinflamatorias, como IL-5 (mepolizumab, reslizumab, benralizumab) e IL-13 (lebrikizumab), son los que tienen más visos de ser utilizados clínicamente. Tal vez el bloqueo de más de una vía de citoquinas (como IL-4 e IL-13 con dulipumab) pueda ofrecer una mayor eficacia del tratamiento, junto con una seguridad aceptable.Referencias
GINA Report. Global Strategy for Asthma Management and Prevention. Revised 2014. Disponible en: http://ginasthma.org/2016-gina-report-global-strategy-for-asthma-management-and-prevention/ [Consultada en octubre de 2014].
Martínez-Moragón E, Serra-Batlles J, De Diego A, Palop M, Casan P, Rubio-Terrés C, et al. [Economic cost of treating the patient with asthma in Spain: the AsmaCost study]. Arch Bronconeumol. 2009;45:481–6.
González Barcala FJ, De la Fuente-Cid R, Álvarez-Gil R, Tafalla M, Nuevo J, Caamaño-Isorna F. [Factors associated with asthma control in primary care patients: the CHAS study]. Arch Bronconeumol. 2010;46:358–63.
Partridge MR, Van der Molen T, Myrseth SE, Busse WW. Attitudes and actions of asthma patients on regular maintenance therapy: the INSPIRE study. BMC Pulm Med. 2006;6:13.
Olaguibel JM, Quirce S, Juliá B, Fernández C, Fortuna AM, Molina J, et al. Measurement of asthma control according to Global Initiative for Asthma guidelines: a comparison with the Asthma Control Questionnaire. Respir Res. 2012;13:50.
Reddel HK, Taylor DR, Bateman ED, Boulet LP, Boushey HA, Busse WW, et al. An official American Thoracic Society/European Respiratory Society statement: asthma control and exacerbations: standardizing endpoints for clinical asthma trials and clinical practice. Am J Respir Crit Care Med. 2009;180:59–99.
Machado NP, Téllez GA, Castaño JC. Anticuerpos monoclonales: desarrollo físico y perspectivas terapéuticas. Infectio. 2006;10:186–97.
Plaza V, Bellido-Casado J, Díaz C, Pérez de Llano L, Sanchis J, Villasante C, et al. Involvement of Spanish pulmonology centers in patient care, postgraduate education and research in asthma: the results of the ATENEA survey. Arch Bronconeumol. 2012;48:114–9.
Schleich FN, Chevremont A, Paulus V, Henket M, Manise M, Seidel L, et al. Importance of concomitant local and systemic eosinophilia in uncontrolled asthma. Eur Respir
J. 2014;44:97–108.
Katz LE, Gleich GJ, Hartley BF, Yancey SW, Ortega HG. Blood eosinophil count is a useful biomarker to identify patients with severe eosinophilic asthma. Ann Am Thorac Soc. 2014;11:531–6.
Fowler SJ, Tavernier G, Niven R. High blood eosinophil counts predict sputum eosinophilia in patients with severe asthma. J Allergy Clin Immunol. 2015;135:822–4.
Crespo A, Giner J, Torrejón M, Belda A, Mateus E, Granel C, et al. Clinical and inflammatory features of asthma with dissociation between fractional exhaled nitric oxide and eosinophils in induced sputum. J Asthma. 2016;53:459–64.
Slavin RG, Ferioli C, Tannenbaum SJ, Martin C, Blogg M, Lowe PJ. Asthma symptom re-emergence after omalizumab withdrawal correlates well with increasing IgE and decreasing pharmacokinetic concentrations. J Allergy Clin Immunol. 2009;123:107–13.
Bousquet J, Rabe K, Humbert M, Chung KF, Berger W, Fox H, et al. Predicting and evaluating response to omalizumab in patients with severe allergic asthma. Respir Med. 2007;101:1483–92.
Rodrigo GJ, Neffen H, Castro-Rodríguez JA. Efficacy and safety of subcutaneous omalizumab vs placebo as add-on therapy to corticosteroids for children and adults with asthma: a systematic review. Chest. 2011;139:28–35.
Vennera MC, Pérez de Llano L, Bardagi S, Ausin P, Sanjuas C, González H, et al. Omalizumab therapy in severe asthma: experience from the Spanish Registry. Some new approaches. J Asthma. 2012;49:416–22.
Hanania NA, Wenzel S, Rosén K, Hsieh HJ, Mosesova S, Choy DF, et al. Exploring the effects of omalizumab in allergic asthma: an analysis of biomarkers in the EXTRA study. Am J Respir Crit Care Med. 2013;187:804–11.
Harris JM, Maciuca R, Bradley MS, Cabanski CR, Scheerens H, Lim H, et al. A randomized trial of the efficacy and safety of quilizumab in adults with inadequately controlled allergic asthma. Respir Res. 2016;17:29.
Cohen ES, Dobson CL, Käck H, Wang B, Sims DA, Lloyd CO, et al. A novel IgE-neutralizing antibody for the treatment of severe uncontrolled asthma. Mabs. 2014;6:756–64.
Gauvreau GM, Arm JP, Boulet LP, Leigh R, Cockcroft DW, Davis BE, et al. Efficacy and safety of multiple doses of QGE031 (ligelizumab) versus omalizumab and placebo in inhibiting allergen-induced early asthmatic responses. J Allergy Clin Immunol. 2016;138:1051–9.
Leckie MJ, Ten Brinke A, Khan J, Diamant Z, O’Connor BJ, Walls CM, et al. Effects of an interleukin-5 blocking monoclonal antibody on eosinophils, airway hyper-responsiveness, and the late asthmatic response. Lancet. 2000;356:2144–8.
Flood-Page PT, Menzies-Gow AN, Kay AB, Robinson DS. Eosinophil’s role remains uncertain as anti-interleukin-5 only partially depletes numbers in asthmatic airway. Am J Respir Crit Care Med. 2003;167:199–204.
Flood-Page P, Swenson C, Faiferman I, Matthews J, Williams M, Brannick L, et al.; International Mepolizumab Study Group. A study to evaluate safety and efficacy of mepolizumab in patients with moderate persistent asthma. Am J Respir Crit Care Med. 2007;176:1062–71.
Nair P, Pizzichini MM, Kjarsgaard M, Inman MD, Efthimiadis A, Pizzichini E, et al. Mepolizumab for prednisone-dependent asthma with sputum eosinophilia. N Eng J Med. 2009;360:985–93.
Haldar P, Brightling CE, Hargadon B, Gupta S, Monteiro W, Sousa A, et al. Mepolizumab and exacerbations of refractory eosinophilic asthma. N Eng J Med. 2009;360:973–84.
Pavord ID, Korn S, Howarth P, Bleecker ER, Buhl R, Keene ON, et al. Mepolizumab for severe eosinophilic asthma (DREAM): a multicentre, double-blind, placebo controlled trial. Lancet. 2012;380:651–9.
Ortega HG, Liu MC, Pavord ID, Brusselle GG, FitzGerald JM, Chetta A, et al.; MENSA Investigators. Mepolizumab treatment in patients with severe eosinophilic asthma. N Engl J Med. 2014;371:1198–207.
Bel EH, Wenzel SE, Thompson PJ, Prazma CM, Keene ON, Yancey SW, et al.; SIRIUS Investigators. Oral glucocorticoid-sparing effect of mepolizumab in eosinophilic asthma. N Engl J Med. 2014;371:1189–97.
Lugogo N, Domingo C, Chanez P, Leigh R, Gilson MJ, Price RG, et al. Long-term Efficacy and Safety of Mepolizumab in Patients With Severe Eosinophilic Asthma: A Multi-Center, Open-Label, Phase IIIb Study. Clin Ther. 2016;38:2058–70.
Magnan A, Bourdin A, Prazma CM, Albers FC, Price RG, Yancey SW, et al. Treatment response with mepolizumab in severe eosinophilic asthma patients with previous omalizumab treatment. Allergy. 2016;71:1335–44.
Castro M, Mathur S, Hargreave F, Boulet LP, Xie F, Young J, et al.; Res-5-0010 Study Group. Reslizumab for poorly controlled, eosinophilic asthma: a randomized, placebo-controlled study. Am J Respir Crit Care Med. 2011;184:1125–32.
Castro M, Zangrilli J, Wechsler ME, Bateman ED, Brusselle GG, Bardin P, et al. Reslizumab for inadequately controlled asthma with elevated blood eosinophil counts: results from two multicentre, parallel, double-blind, randomised, placebo-controlled, phase 3 trials. Lancet Respir Med. 2015;3:355–66.
Bjermer L, Lemière C, Maspero J, Weiss S, Zangrilli J, Germinaro M. Reslizumab for Inadequately Controlled Asthma with Elevated Blood Eosinophil Levels: a Randomized Phase 3 Study. Chest. 2016;150:789–98.
Corren J, Weinstein S, Janka L, Zangrilli J, Garin M. Phase 3 Study of Reslizumab in Patients with Poorly Controlled Asthma: Effects Across a Broad Range of Eosinophil Counts. Chest. 2016;150:799–810.
Li J, Lin C, Du J, Xiao B, Du C, Sun J, et al. The efficacy and safety of Reslizumab for inadequately controlled asthma with elevated blood eosinophil counts: a systematic review and meta-analysis. J Asthma. 2016 Jul 19:0. [Epub ahead of print].
Busse WW, Katial R, Gossage D, Sari S, Wang B, Kolbeck R, et al. Safety profile, pharmacokinetics, and biologic activity of MEDI-563, an anti-IL-5 receptor alpha antibody, in a phase I study of subjects with mild asthma. J Allergy Clin Immunol. 2010;125:1237–44.
Laviolette M, Gossage DL, Gauvreau G, Leigh R, Olivenstein R, Katial R, et al. Effects of benralizumab on airway eosinophils in asthmatic patients with sputum eosinophilia. J Allergy Clin Immunol. 2013;132:1086–96.
Castro M, Wenzel SE, Bleecker ER, Pizzichini E, Kuna P, Busse WW, et al. Benralizumab, an anti-interleukin 5 receptor α monoclonal antibody, versus placebo for uncontrolled eosinophilic asthma: a phase 2b randomised dose-ranging study. Lancet Respir Med. 2014;2:879–90.
Nowak RM, Parker JM, Silverman RA, Rowe BH, Smithline H, Khan F, et al. A randomized trial of benralizumab, an antiinterleukin 5 receptor α monoclonal antibody, after acute asthma. Am J Emerg Med. 2015;33:14–20.
Pham TH, Damera G, Newbold P, Ranade K. Reductions in eosinophil biomarkers by benralizumab in patients with asthma. Respir Med. 2016;111:21–9.
Brightling CE, Bleecker ER, Panettieri RA Jr, Bafadhel M, She D, Ward CK, et al. Benralizumab for chronic obstructive pulmonary disease and sputum eosinophilia: a randomised, double-blind, placebo-controlled, phase 2a study. Lancet Respir Med. 2014;2:891–901.
FitzGerald JM, Bleecker ER, Nair P, Korn S, Ohta K, Lommatzsch M, et al.; CALIMA study investigators. Benralizumab, an anti-interleukin-5 receptor α monoclonal antibody, as add-on treatment for patients with severe, uncontrolled, eosinophilic asthma (CALIMA): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2016;S0140-6736:31322–8.
Bleecker ER, FitzGerald JM, Chanez P, Papi A, Weinstein SF, Barker P, et al.; SIROCCO study investigators. Efficacy and safety of benralizumab for patients with severe asthma uncontrolled with high-dosage inhaled corticosteroids and long-acting β2-agonists (SIROCCO): a randomised, multicentre, placebo-controlled phase 3 trial. Lancet. 2016;S0140-6736:31324–1. [Epub ahead of print].
Oh CK, Geba GP, Molfino N. Investigational therapeutics targeting the IL-4/IL- 13/STAT-6 pathway for the treatment of asthma. Eur Respir Rev. 2010;19:46–54.
Wenzel S, Wilbraham D, Fuller R, Longphre M. Effect of an interleukin-4 variant on late phase asthmatic response to allergen challenge in asthmatic patients: results of two phase 2a studies. Lancet. 2007;370:1422–31.
Antoniu SA. Pitrakinra, a dual IL-4/IL-13 antagonist for the potential treatment of asthma and eczema. Curr Opin Investig Drugs. 2010;11:1286–94.
Borish LC, Nelson HS, Lanz MJ, Claussen L, Whitmore JB, Agostí JM, et al. Interleukin-4 receptor in moderate atopic asthma. A phase I/II randomized, placebo-controlled trial. Am J Respir Crit Care Med. 1999;160:1816–23.
Borish LC, Nelson HS, Corren J, Bensch G, Bussen WW, Whitmore JB, et al.; IL-4R Asthma Study Group. Efficacy of soluble IL-4 receptor for the treatment of adults with asthma. J Allergy Clin Immunol. 2001;107:963–70.
Corren J, Busse W, Meltzer EO, Mansfield L, Bensch G, Fahrenholz J, et al. A randomized, controlled, phase 2 study of AMG 317, an IL-4Ralpha antagonist, in patients with asthma. Am J Respir Crit Care Med. 2010;181:788–96.
Wenzel S, Ford L, Pearlman D, Spector S, Sher L, Skobieranda F, et al. Dupilumab in persistent asthma with elevated eosinophil levels. N Engl J Med. 2013;368:2511–3.
Wenzel S, Castro M, Corren J, Maspero J, Wang L, Zhang B, et al. Dupilumab efficacy and safety in adults with uncontrolled persistent asthma despite use of medium-to-high-dose inhaled corticosteroids plus a long-acting β2 agonist: a randomised double-blind placebo-controlled pivotal phase 2b dose-ranging trial. Lancet. 2016;388: 31–44.
Corren J, Lemanske RF, Hanania NA, Korenblat PE, Parsey MV, Arron JR, et al. Lebrikizumab treatment in adults with asthma. N Engl J Med. 2011;365:1088–98.
Hanania NA, Noonan M, Corren J, Korenblat P, Zheng Y, Fischer SK, et al. Lebrikizumab in moderate-to-severe asthma: pooled data from two randomised placebo-controlled studies. Thorax. 2015;0:1–9.
Noonan M, Korenblat P, Mosesova S, Scheerens H, Arron JR, Zheng Y, et al. Dose-ranging study of lebrikizumab in asthmatic patients not receiving inhaled steroids. J Allergy Clin Immunol. 2013;132:567–74.
Scheerens H, Arron JR, Zheng Y, Putnam WS, Erickson RW, Choy DF, et al. The effects of lebrikizumab in patients with mild asthma following whole lung allergen challenge. Clin Exp Allergy. 2014;44:38–46.
Gauvreau GM, Boulet LP, Cockroft DW, Baatjes A, Cote J, Deschesnes F, et al. Antisense therapy against CCR3 and the common beta chain attenuates allergen induced eosinophilic responses. Am J Resp Crit Care Med. 2008;177:952–8.
Piper E, Brightling C, Niven R, Oh C, Faggioni R, Poon K, et al. A phase II placebo-controlled study of tralokinumab in moderate-to-severe asthma. Eur Respir J. 2013;41:330–8.
Brithling CE, Chanez P, Leigh R, O’Byrne PM, Korn S, She D, et al. Efficacy and safety of tralokinumab in patients with severe uncontrolled asthma: a randomised, double-blind, placebo-controlled, phase 2b trial. Lancet Respir Med. 2015;3:692–701.
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