Migraine treatment with biological therapies. The state of the art / Tratamento da enxaqueca com terapias biológicas. O Estado da arte

Migraine is a highly prevalent and debilitating neurological disorder. Most patients do not receive a correct diagnosis and effective treatments. Apart of the few specialists and tertiary centers worldwide, the treatment of migraine is usually symptomatic and prevention, as well as treatments of the underlying mechanisms, are not aimed. It results in frustration and substantial burden. The last few years witnessed the releasing of specific biological therapies, mostly addressing one of the peptides involved in migraine pathophysiology, the calcitonin gene-related peptide (CGRP). Either the small molecules as well as the monoclonal antibodies against CGRP or its canonical receptor have been launched in markets across the globe and represent interesting options for the treatment of migraine. Onabotulinumtoxin A has also been proposed for chronic migraine as well, but not for episodic migraine, based on its unique ability to inhibit the SNARE complex formation and the release of numerous potential mediators of migraine. However, despite the favorable figures on efficacy and tolerability of these compounds, the regulations, and particulars of different countries, regarding the structures and reimbursement of medical care, demonstrated different adhesion profiles of chosen populations to receive these emerging weapons against migraine-imposed suffering. This review addresses the use and characteristics of biological therapies used in migraine treatment.

A enxaqueca é um distúrbio neurológico altamente prevalente e debilitante. A maioria dos pacientes não recebe um diagnóstico correto e tratamentos eficazes. Com exceção dos poucos especialistas e centros terciários em todo o mundo, o tratamento da enxaqueca é geralmente sintomático e a prevenção, bem como o tratamento dos mecanismos subjacentes, não são direcionados. Isso resulta em frustração e fardo substancial. Os últimos anos testemunharam o lançamento de terapias biológicas específicas, abordando principalmente um dos peptídeos envolvidos na fisiopatologia da enxaqueca, o peptídeo relacionado ao gene da calcitonina (CGRP). Tanto as pequenas moléculas como os anticorpos monoclonais contra CGRP ou o seu receptor canônico foram lançados em mercados em todo o mundo e representam opções interessantes para o tratamento da enxaqueca. A onabotulinumtoxina A também foi proposta para enxaqueca crônica, mas não para enxaqueca episódica, com base em sua capacidade única de inibir a formação do complexo SNARE e a liberação de numerosos mediadores potenciais da enxaqueca. No entanto, apesar dos números favoráveis ​​sobre a eficácia e tolerabilidade destes compostos, os regulamentos e particularidades de diferentes países, no que diz respeito às estruturas e reembolso dos cuidados médicos, demonstraram diferentes perfis de adesão das populações escolhidas para receber estas armas emergentes contra o sofrimento imposto pela enxaqueca. Esta revisão aborda o uso e as características das terapias biológicas utilizadas no tratamento da enxaqueca.

Cartílago de tiburón: una panacea oncológica más / Shark cartilage: another oncological panacea

Resumen El cáncer es la tercera causa de muerte después de las enfermedades cardiovasculares y diabetes (mellitus); ante tan desolador panorama epidemiológico, es esperable que surjan multitud de terapias "curativas" no convencionales, biológicas y no biológicas. Entre las terapias biológicas se encuentra el cartílago de tiburón, cuyos defensores de su consumo se basan en la falsa premisa de que "los tiburones no tienen cáncer", y cuando son confrontados, alegan teorías conspiranoicas. Aunque se ha demostrado la existencia de un factor inhibidor de angiogénesis en el producto, los ensayos clínicos no han sido concluyentes en cuanto a un efecto benéfico neto en pacientes oncológicos. Pero el mercadeo popular de la sustancia es un negocio de varios millones de dólares anuales. Es prudente que los médicos tengan conocimiento incluso de los posibles efectos colaterales para proporcionar información a los pacientes.

Abstract Cancer is the third cause of death after cardiovascular diseases and diabetes mellitus. In the face of such a devastating epidemiological panorama, it is expected that a multitude of non-conventional, biological and non-biological "curative" therapies will emerge. Among the biological therapies is the shark cartilage, whose defenders of its use are based on the false premise that "sharks do not have cancer", and when confronted, they claim conspiracy theories. Although the presence of an inhibitory factor of angiogenesis in the product has been demonstrated, clinical trials have not been conclusive as to a net beneficial effect in oncological patients. But the popular marketing of the substance is a business of several million dollars a year. It is prudent that doctors have knowledge, including possible side effects, to provide information to patients.

Risk of Herpes Zoster in Patients with Rheumatoid Arthritis Undergoing Biologic Disease-Modifying Therapy

OBJECTIVE: Rheumatoid arthritis (RA) patients suffer from an increased risk of herpes zoster (HZ) partially due to immunosuppressant medications. This study investigated HZ in RA patients treated with biologic disease-modifying antirheumatic drugs (bDMARDs), as compared with conventional DMARDs (cDMARDs). METHODS: This retrospective case series study assembled record information of 277 RA patients who received bDMARDs after failure of at least one cDMARDs at Seoul National University Hospital between August 2003 and February 2015. Following capture of baseline information and identification of HZ episodes, crude HZ incidence rates per 100 patient-years (95% confidence intervals) were calculated. RESULTS: For 718 treatment courses, 277 (38.6%) comprised cDMARDs, 66 (9.2%) infliximab, 175 (24.4%) etanercept, 95 (13.2%) adalimumab, 9 (1.3%) golimumab, 41 (5.7%) rituximab, 31 (4.3%) abatacept, and 24 (3.3%) tocilizumab. There were 37 HZ episodes, 16 during cDMARD treatment courses, and 21 accompanying bDMARDs, two with infliximab, eight with etanercept, five with adalimumab, and three each with rituximab and abatacept. The crude HZ incidence rate per 100 patient-years was 2.4 (1.4∼3.9) for cDMARDs, 2.2 (0.3∼7.9) for infliximab, 1.8 (0.8∼3.6) for etanercept, 3.7 (1.2∼8.4) for adalimumab, 3.9 (0.8∼11.0) for rituximab, and 8.5 (1.8∼23.1) for abatacept. CONCLUSION: We conclude that bDMARDs do not always increase the risk of HZs in RA patients, although HZ rates vary for different bDMARDs.

Current and Emerging Biologics for Ulcerative Colitis

Conventional medical treatment for ulcerative colitis can have limited efficacy or severe adverse reactions requiring additional treatment or colectomy. Hence, different biological agents that target specific immunological pathways are being investigated for treating ulcerative colitis. Anti-tumor necrosis factor (TNF) agents were the first biologics to be used for treating inflammatory bowel disease. For example, infliximab and adalimumab, which are anti-TNF agents, are being used for treating ulcerative colitis. Recently, golimumab, another anti-TNF agent, and vedolizumab, an anti-adhesion therapy, have been approved for ulcerative colitis by the U.S. Food and Drug Administration. In addition, new medications such as tofacitinib, a Janus kinase inhibitor, and etrolizumab, another anti-adhesion therapy, are emerging as therapeutic agents. Therefore, there is a need for further studies to select appropriate patient groups for these biologics and to improve the outcomes of ulcerative colitis treatment through appropriate medical usage.