COX-2 Inhibition: What We Learned—A Controversial Update on Safety Data

Katz, Jeffrey A.

doi:10.1111/pme.12252

Cited by 33 publications

(28 citation statements)

References 31 publications

(31 reference statements)

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“…According to a population-based study, the drugs most frequently used for OA therapy are chondroitin (21.2%), glucosamine (15.8%) and oral NSAIDs (14.4%), and the incidence of the use of opioids, cyclooxygenase-2 (COX-2) inhibitors and chondroitin increased over 5-year period, whereas all others have decreased [8]. Although COX-2 inhibitors have incidence of lower gastrointestinal side effects, its cardiovascular risk should be carefully monitored when it is used for each patient [9].…”

Section: Current Treatment Of Oamentioning

confidence: 98%

Investigational drugs for the treatment of osteoarthritis

Wang

Hunter

et al. 2015

Expert Opinion on Investigational Drugs

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Section: Current Treatment Of Oamentioning

confidence: 98%

Investigational drugs for the treatment of osteoarthritis

Wang

Hunter

et al. 2015

Expert Opinion on Investigational Drugs

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“…Side effects related to the use of NSAIDs have been widely reported in numerous studies (33)(34). Similarly, Coxibs are burdened by various and sometimes severe cardiovascular side effects, that may prevent patients from accessing this kind of therapy on the long course (35,36). Regarding opioids, their use is restricted to cases where NSAIDs/Coxibs cannot provide sufficient pain relief or where they are contraindicated due to underlying hypertension or hepatic or renal impairment.…”

Section: The Uncertainty Of Analgesic Treatment In Oamentioning

confidence: 98%

An update on the up and coming therapies to treat osteoarthritis, a multifaceted disease

Roman‐Blas

Bizzi

Largo

et al. 2016

Expert Opinion on Pharmacotherapy

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Despite the renewed interest in the search of new compounds for treatment of OA, results have been limited. Novel systemic and IA administered agents are in active development. IA drug administration is particularly an attractive approach because can diminish some of the severe side effects associated with systemic drugs. Indeed, one of the most promising fields for pharmacology innovation in OA is joint injected therapy, as suggested by preliminary data from recent studies using IA sprifermin (rhFGF-18), mesenchymal stem cells or TGF-B1 transduced allogenic chondrocytes. Last, the effort to develop new drugs must be accompanied by the interest for establishing well-defined phenotypes, and only then, a more tailored therapy should be practiced in OA.

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“…Compared to mixed COX-1/COX-2 inhibitors such as aspirin, the selective COX-2 inhibitors show fewer gastrointestinal side effects such as bleeding but a higher rate of cardiovascular side effects (Katz 2013 ). In a placebo-controlled study of rofecoxib-withdrawn from the market because of cardiovascular side effects-the increased relative risk for a cardiovascular event became apparent after 18 months of treatment; during the fi rst 18 months, the event rates were similar in the rofecoxib and placebo groups.…”

Section: Risks Associated With Cox-2 Inhibitorsmentioning

confidence: 98%

Immunomodulation as Therapeutic Approach in Schizophrenia and Depression: State of the Art

Müller

2015

Current Topics in Neurotoxicity

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Infl ammation has been discussed for decades as an underlying cause of psychiatric disorders such as major depression (MD) and schizophrenia. Almost a hundred years ago, an anti-infl ammatory therapeutic approach, so-called vaccination therapy, was proposed by Wagner von Jauregg. In schizophrenia and MD, opposite patterns of the type-1 and type-2 immune response seem to be associated with differences in the activation of the enzyme indoleamine 2,3-dioxygenase (IDO) and in tryptophan-kynurenine metabolism. These differences are associated with an imbalance in glutamatergic neurotransmission, which may contribute to an excess of N -methyl-D -aspartate (NMDA) agonism in depression and NMDA antagonism in schizophrenia. In both schizophrenia and depression the immunological imbalance results in increased prostaglandin E 2 (PE 2 ) production and probably also in increased cyclooxygenase-2 (COX-2) expression. Although there is strong evidence for the view that the interactions of the immune system, IDO, serotonergic system and glutamatergic neurotransmission play a key role in schizophrenia and depression, several gaps remain that need to be closed by intense research. Accordingly, anti-infl ammatory or immune-modulating substances might have benefi cial effects in schizophrenia and MD. COX-2 inhibitors have shown encouraging results in animal models. Moreover, during the last decade many clinical studies have been performed with COX-2 inhibitors, mostly celecoxib, in schizophrenia and MD. For ethical reasons, all these studies used an add-on design, i.e. the COX-2 inhibitor was given adjunctive to either antipsychotics (in schizophrenia) or antidepressants (in MD). Although an add-on design is a methodological challenge, favourable effects of COX-2 inhibitors were observed in placebo-controlled double-blind studies in both indications. Meta-analytic studies proved a signifi cant therapeutic effect of COX-2 inhibitors in MD and in early stages of schizophrenia. Other pharmacological approaches based on N. Müller (*) Department of Psychiatry and Psychotherapy , Ludwig-Maximilians University Munich , Nussbaumstr. 7 , 80336 Munich , Germany e-mail: Norbert.Mueller@med.uni-muenchen.de 352 immunological effects are discussed. Anti-infl ammatory and immune-modulating compounds are promising but still need careful further scientifi c evaluation, including clinical studies in larger samples of patients.

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COX-2 Inhibition: What We Learned—A Controversial Update on Safety Data

Abstract: The entire "COX-2 debacle" is reminiscent of past events with NSAIDs. Amid this public, media, and political hysteria, it is not clear if we will see any more NSAIDs (selective or otherwise) approved in the near future.

Cited by 33 publications

References 31 publications

Investigational drugs for the treatment of osteoarthritis

Investigational drugs for the treatment of osteoarthritis

An update on the up and coming therapies to treat osteoarthritis, a multifaceted disease

Immunomodulation as Therapeutic Approach in Schizophrenia and Depression: State of the Art

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