12 Jahre Celecoxib – eine Bestandsaufnahme

 

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Zusammenfassung

Die Therapie mit traditionellen, nichtselektiven Antirheumatika (t-NSAR) kann zu schwerwiegenden Schäden des Gastrointestinaltrakts bis hin zu fatalen Blutungen führen, wobei vor allem Pa­tienten mit einer Ulkusanamnese und Menschen jenseits des sechzigsten Lebensjahrs gefährdet sind. Aus diesem Umstand und der Tatsache, dass diese Präparate in unserer alternden Gesellschaft unverzichtbar für die Behandlung von Schmerzen des Bewegungsapparates sind, ergab sich ein dringender Bedarf für besser verträgliche Substanzen. Eine neue, Cyclooxygenase 2 selektive Substanzklasse versprach, diese Anforderungen zu erfüllen. Nach nunmehr 12 Jahren klinischer Erfahrung mit der Substanz Celecoxib soll in dieser Arbeit die Bedeutung dieses Wirkstoffs aktualisiert betrachtet werden. Für Celecoxib wurde bei sämtlichen untersuchten rheumatischen Erkrankungen eine mit diversen traditionellen NSAR vergleichbare Wirksamkeit belegt, bei Spondylitis ankylosans hemmt eine regelmäßige antiphlogistische Therapie mit Celecoxib die radiologische Krankheitsprogression signifikant. Umfangreiche Sicherheitsstudien der vergangenen Jahre zeigten weiter, dass das Schadpotenzial von Celecoxib am oberen Gastrointestinaltrakt jenem einer Kombinationstherapie von Diclofenac und einem Protonenpumpeninhibitor entspricht. Bei Hochrisikopatienten läßt sich das Blutungsrisiko am oberen GI-Trakt noch weiter reduzieren, wenn man Celecoxib mit einem PPI kombiniert. Auch die im Vergleich zu Schädigungen des oberen GI-Trakts mit einer sogar höheren Mortalität gekennzeichnete Schadwirkung der NSAR am unteren GI-Trakt tritt unter Celecoxib in signifikant geringerem Ausmaß auf. Das gas­trointestinale Schadpotenzial von Antiphlogistika erhöht sich bei Koadministration gerinnungshemmender Substanzen um ein Mehrfaches, jedoch auch Antidepressiva, insbesondere SSRI, erhöhen das Blutungsrisiko, welches durch Celecoxib im Vergleich zu t-NSAR signifikant gesenkt wird. Die kardiovaskulären Risiken von t-NSAR, insbesondere für Diclofenac und Ibuprofen, haben gegenüber den gastrointestinalen einen deutlich geringeren Stellenwert, jedoch konnte für Celecoxib in fast allen Metaanalysen eine im Vergleich zu t-NSAR geringere oder gar keine Risikoerhöhung für CV-Ereignisse gezeigt werden, lediglich Naproxen hat ein noch diskret geringeres CV-Risiko. Aufgrund seiner vorteilhaften Sicherheit und den antiproliferativen Effekten ist Celecoxib weiterhin Gegenstand intensiver Forschung, u. a. in verschiedenen Tumorindikationen.

Abstract

Serious complications of the gastrointestinal tract are a major problem of traditional (t)NSAIDs. Patients are at increased risk, if they have had one or more previous ulcer(s) or are aged above 60 years. Because of this and considering the average age in western countries is steadily increasing, a need for these drugs is essen­tial, however an improved tolerability was desperately required. Cyclooxygenase-2-inhibitors – a new class of anti-inflammatory drugs – were developed and promised to meet these needs.

This article reflects 12 years of clinical experience with celecoxib and presents most recent data in comparison to other NSAIDs.

Celecoxib has a comparable efficacy to all other NSAIDs in the treatment of rheumatic disorders. Evidence even exists, showing celecoxib to halt the radiographic progression in Ankylosing Spondylitis, significantly.

Good tolerability was shown for the upper GI-tract which was similar to a tNSAID combined with a PPI. A better tolerability of celecoxib was detected for the lower GI-tract. This is important due to a higher mortality from lower GI-complications.

The iatrogenic risk of NSAIDs increases when concomitant medication like SSRI or anti-coagulants are administered. To encounter damages in patients with additional risk factors, celecoxib could be combined with a PPI.

Cardiovascular side effects are much less in comparison to GI-events. Diclofenac seems to have the highest CV-risk, whereas celecoxib revealed a marginal increase only or no risk elevation in almost all meta-analyses. Solely naproxen tends to have an even lower CV-risk.

Celecoxib displays a good efficacy and beneficial safety profile and is still a matter of research, for example in cancer research according to its anti-proliferative capacity.

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