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001-es BibID:	BIBFORM015816
Első szerző:	Gerlag, Danielle M.
Cím:	Preclinical and clinical investigation of a CCR5 antagonist, AZD5672, in patients with rheumatoid arthritis receiving methotrexate / Gerlag, D. M., Hollis, S., Layton, M., Vencovsky, J., Szekanecz, Z., Braddock, M., Tak, P. P., The ESCAPE Study Group
Dátum:	2010
ISSN:	1529-0131 (Electronic)
Megjegyzések:	To investigate both the preclinical effects of blocking the chemokine receptor CCR5 and the clinical effects of this approach on the signs and symptoms of rheumatoid arthritis (RA) in patients with active disease. METHODS: Preclinical evaluations of AZD5672, a small-molecule antagonist of CCR5, were performed, including studies of ligand binding and chemotaxis. The pharmacokinetics of AZD5672 were assessed in both single- and multiple-dose studies in healthy volunteers. A randomized, placebo-controlled, phase IIb study was conducted in patients with active RA receiving methotrexate. Treatment arms were AZD5672 (20, 50, 100, or 150 mg orally, once daily), matched placebo, or open-label etanercept (50 mg subcutaneously, once weekly). The primary end point was the proportion of patients achieving a 20% improvement response on the American College of Rheumatology improvement criteria (ACR20) at week 12. Secondary end points included the ACR20 over time, as well as 50% (ACR50) and 70% (ACR70) improvement responses, changes in individual components of the ACR improvement criteria, and disease activity measured with the Disease Activity Score based on the 28-joint count. RESULTS: AZD5672 was a highly potent and selective antagonist of CCR5, displaying nonproportional steady-state pharmacokinetics while inhibiting internalization of CCR5 in an ex vivo macrophage inflammatory protein 1beta stimulation assay in which AZD5672 was evaluated over the 20-150-mg dose range. In the phase IIb study testing this dose range in patients with RA (n = 371 patients randomized to received treatment), AZD5672 was generally well tolerated, with no unexpected adverse events. There was no statistically significant difference in the proportion of patients achieving an ACR20 response at week 12 between those receiving any dose of AZD5672 and those receiving placebo; etanercept was significantly more efficacious than AZD5672 and placebo. CONCLUSION: Despite a clear rationale for targeting CCR5, this clinical study showed that AZD5672, administered orally, did not have any clinical benefit, suggesting that CCR5 antagonism alone is unlikely to be a viable therapeutic strategy in RA.
Tárgyszavak:	Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban Antirheumatic Agents/therapeutic use Arthritis, Rheumatoid/drug therapy Benzeneacetamides/therapeutic use Chi-Square Distribution Double-Blind Method Drug Therapy, Combination Female Humans Male Methotrexate/therapeutic use Receptors, CCR5/antagonists & inhibitors Sulfonamides/*therapeutic use Treatment Outcome
Megjelenés:	Arthritis and Rheumatism. - 62 : 11 (2010), p. 3154-3160. -
További szerzők:	Hollis, Sally Layton, Mark Vencovsky, Jiri Szekanecz Zoltán (1964-) (reumatológus, belgyógyász, immunológus) Braddock, Martin Tak, Paul P. The ESCAPE Study Group
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001-es BibID:	BIBFORM081583
035-os BibID:	(WOS)000531365800016 (Scopus)85075957157
Első szerző:	Szekanecz Zoltán (reumatológus, belgyógyász, immunológus)
Cím:	Cigarette smoking and clinical response to certolizumab pegol treatment in Hungarian, Czech, and Slovak patients with rheumatoid arthritis : 104-week data from the CIMDORA prospective, non-interventional study / Z. Szekanecz, Á. Koncz, J. Dunkel, J. Vencovský, CIMDORA collaborators
Dátum:	2019
Megjegyzések:	Objective Smoking has been shown to influence rheumatoid arthritis (RA) severity and reduce response to some anti-tumour necrosis factor (anti-TNF) therapies. CIMDORA assessed the association between cigarette smoking and clinical effectiveness of certolizumab pegol (CZP) in Hungarian, Slovak, and Czech RA patients. Methods CIMDORA was a prospective, non-interventional, 104-week study (Feb 2011?Aug 2015). The primary endpoint was association between change in 28-joint Disease Activity Score (DAS28[ESR]) from baseline to Week 12, and baseline cigarette pack-year history. Secondary endpoints included association between change in DAS28(ESR) and daily number of cigarettes smoked. The full analysis set (FAS) included all patients receiving ?1 dose of CZP with all necessary assessments for the primary endpoint. Treatment-emergent adverse events (TEAEs) were reported for all patients receiving ?1 dose of CZP. Results The FAS included 218/273 enrolled patients: 155 Hungarian, 46 Czech and 17 Slovak. Hungarian and Czech patients completed 104 weeks (n=141); Slovak patients completed 52 weeks. Mean change in DAS28(ESR) [SD] at Week 12 (-2.78 [1.47]) was not significantly associated with baseline cigarette pack-year history (slope estimate [SE]: 0.03, 95% confidence interval [CI]: -0.16, 0.21 [p=0.77]). Mean DAS28(ESR) [SD] reductions to Week 52 (-3.33 [1.33]) were not significantly associated with daily number of cigarettes smoked in the previous month (SE: 0.001, CI: -0.05, 0.05 [p=0.95]). Two deaths were reported but neither of them was related to CZP. No new safety signals were identified and the safety profile was consistent with previous CZP studies. Conclusion After 104 weeks of CZP treatment, patients demonstrated similar DAS28(ESR) improvements, irrespective of smoking history.
Tárgyszavak:	Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk rheumatoid arthritis cigarette smoking anti-rheumatic agents tumour necrosis factor-alpha
Megjelenés:	Clinical and Experimental Rheumatology. - 37 : 6 (2019), p. 1010-1018. -
További szerzők:	Koncz Ágnes Dunkel, J. Vencovsky, Jiri CIMDORA collaborators
Internet cím:	Intézményi repozitóriumban (DEA) tárolt változat
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001-es BibID:	BIBFORM070459
Első szerző:	Szekanecz Zoltán (reumatológus, belgyógyász, immunológus)
Cím:	Opportunities and challenges in rheumatology research in Central Europe / Szekanecz Zoltán, Anic Branimir, Héjj Gábor, Holc Iztok, Hunka Aniella, Kucharz Eugene, Machold Klaus, Mayer Miroslav, Pahor Artur, Puchner Rudolf, Rovensky Jozef, Senolt Ladislav, Tuchynova Alena, Vencovsky Jiri, Smolen Josef S.
Dátum:	2017
ISSN:	1478-6354 1478-6362
Megjegyzések:	The Central European Congress of Rheumatology(CECR) has been organized by seven Central Europeancountries: Austria, Croatia, Czech Republic, Hungary,Poland, Slovakia, and Slovenia. These countries havelots of similarities, but also differences, with respectto rheumatology research. In this paper, based onquestionnaires, we wish to demonstrate achievementsand difficulties in rheumatology research performedin our region.
Tárgyszavak:	Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban Central Europe Rheumatology Research Funding Arthritis Collaboration
Megjelenés:	Arthritis Research & Therapy 19 : 196 (2017), p. 1-4. -
További szerzők:	Anic, Branimir Héjj Gábor Holc, Iztok Hunka Aniella Kucharz, Eugene Machold, Klaus Mayer, Miroslav Pahor, Artur Puchner Rudolf Rovensky, Josef Senolt, Ladislav Tuchynova, Alena Vencovsky, Jiri Smolen, Josef S.
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