Publications by authors named "C Jentzsch"

11 Publications

Magnetic resonance imaging characteristics in patients with spondyloarthritis and clinical diagnosis of heel enthesitis: post hoc analysis from the phase 3 ACHILLES trial.

Arthritis Res Ther 2022 05 16;24(1):111. Epub 2022 May 16.

CIRI/Rheumatology and Fraunhofer TMP, Goethe-University, Frankfurt, Germany.

Objective: To investigate the imaging characteristics and clinically assess heel enthesitis in spondyloarthritis (SpA) by applying in a post hoc analysis the Heel Enthesitis Magnetic Resonance Imaging Scoring system (HEMRIS) in blinded and centrally-read MRI data from the ACHILLES trial (NCT02771210).

Methods: ACHILLES included patients (≥18 years) with active psoriatic arthritis or axial SpA with clinical and MRI-positive heel enthesitis refractory to standard treatment. Patients were randomized to receive subcutaneous secukinumab 150/300 mg or placebo. At week 24, patients on placebo were switched to secukinumab treatment. MRI-positive heel enthesitis was confirmed in all patients by local investigators. MRIs were performed at 3 timepoints: screening and weeks 24 and 52. In the present analysis, all MRIs were re-evaluated by 2 blinded central readers in a consensus read fashion for a priori defined MRI parameters based on HEMRIS.

Results: At screening, 171/204 (83.8%) of patients presented with entheseal inflammation and/or structural damage, considering both the Achilles tendon and plantar fascia. Pathologies were more evident in the Achilles tendon area compared to the plantar aponeurosis. The most frequent pathologies were intra-tendon hypersignal and retrocalcaneal bursitis. The mean total entheseal inflammation score at screening in the Achilles tendon area was 2.99 (N=204) and the mean change (standard deviation [SD]) from screening to weeks 24 and 52 was - 0.91 (1.99) and - 0.83 (2.12) in the secukinumab group vs - 0.48 (1.86) and - 0.80 (1.98) in the placebo-secukinumab group, respectively. The mean total structural damage score at screening was 1.36 (N=204) and the mean change (SD) from screening to weeks 24 and 52 was 0.00 (0.65) and - 0.06 (0.56) in the secukinumab group vs 0.08 (0.48) and 0.04 (0.75) in the placebo-secukinumab group, respectively.

Conclusions: Based on the newly developed HEMRIS, entheseal inflammation and/or structural damage was confirmed in 83.3% of ACHILLES patients. Pathologies were more evident in the Achilles tendon area compared to plantar fascia, with the inflammatory parameters being more responsive with secukinumab treatment compared to placebo. The present analysis, with detailed information on individual MRI parameters, contributes to the scientific debate on heel enthesitis.

Trial Registration: ClinicalTrials.gov NCT02771210 .
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http://dx.doi.org/10.1186/s13075-022-02797-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9109380PMC
May 2022

Efficacy and safety of secukinumab in patients with spondyloarthritis and enthesitis at the Achilles tendon: results from a phase 3b trial.

Rheumatology (Oxford) 2022 07;61(7):2856-2866

Rheumazentrum Ruhrgebiet-Ruhr-University Bochum, Herne, Germany.

Objective: ACHILLES aimed to demonstrate efficacy of secukinumab on Achilles' tendon enthesitis in spondyloarthritis (SpA) patients.

Methods: Patients ≥18 years (n = 204) with active PsA or axial SpA and heel enthesitis were randomized 1:1 to secukinumab 150/300 mg or placebo up to week 24, and thereafter placebo patients were switched to secukinumab.

Results: At week 24, a higher, yet statistically non-significant (P = 0.136), proportion of patients in secukinumab vs placebo reported resolution of Achilles tendon enthesitis in affected foot (42.2% vs 31.4%; odds ratio [OR] = 1.63; 95% CI: 0.87, 3.08). Proportion of patients reporting resolution of enthesitis based on Leeds Enthesitis Index was higher with secukinumab vs placebo (33.3% vs 23.5%; OR = 1.65; 95% CI: 0.85, 3.25) at week 24. Mean change from baseline in heel pain at week 24 was higher in secukinumab patients vs placebo (-2.8 [3.0] vs -1.9 [2.7]). Greater improvements with secukinumab were observed in heel enthesopathy activity and global assessment of disease activity. Imaging evaluation by local reading confirmed heel enthesitis on MRI at screening for all patients. Based on central reading, 56% presented with bone marrow oedema and/or tendinitis; according to Heel Enthesitis MRI Scoring System (HEMRIS) post hoc analysis, 76% had signs of entheseal inflammation while 86% had entheseal inflammation and/or structural changes.

Conclusion: A substantial proportion of patients showed no signs of inflammation on the centrally read MRIs despite a clinical diagnosis of heel enthesitis, thus highlighting that the discrepancy between the clinical and imaging assessments of enthesitis requires further investigation. Although ACHILLES did not meet the primary end point, the study reported clinically meaningful improvements in patient-related outcomes.

Trial Registration: clinicaltrials.gov, NCT02771210.
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http://dx.doi.org/10.1093/rheumatology/keab784DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9258542PMC
July 2022

Efficacy and safety of secukinumab in patients with giant cell arteritis: study protocol for a randomized, parallel group, double-blind, placebo-controlled phase II trial.

Trials 2021 Aug 17;22(1):543. Epub 2021 Aug 17.

Department Innere Medizin, Klinik für Rheumatologie und Klinische Immunologie, Vaskulitiszentrum Freiburg, Universitätsklinikum Freiburg, Hugstetterstrasse 55, D-79106, Freiburg, Germany.

Background: One key pathological finding in giant cell arteritis (GCA) is the presence of interferon-gamma and interleukin (IL)-17 producing T helper (Th) 1 and Th17 cells in affected arteries. There is anecdotal evidence of successful induction and maintenance of remission with the monoclonal anti-IL-17A antibody secukinumab. Inhibition of IL-17A could therefore represent a potential new therapeutic option for the treatment of GCA.

Methods: This is a randomized, parallel-group, double-blind, placebo-controlled, multi-center, phase II study in which patients, treating physicians, and the associated clinical staff as well as the sponsor clinical team are blinded. It is designed to evaluate efficacy and safety of secukinumab compared to placebo in combination with an open-label prednisolone taper regimen. Patients included are naïve to biological therapy and have newly diagnosed or relapsing GCA. Fifty patients are randomly assigned in a 1:1 ratio to receive either 300 mg secukinumab or placebo subcutaneously at baseline, weeks 1, 2 and 3, and every 4 weeks from week 4. Patients in both treatment arms receive a 26-week prednisolone taper regimen. The study consists of a maximum 6-week screening period, a 52-week treatment period (including the 26-week tapering), and an 8-week safety follow-up, with primary and secondary endpoint assessments at week 28. Patients who do not achieve remission by week 12 experience a flare after remission or cannot adhere to the prednisolone tapering will enter the escape arm and receive prednisolone at a dose determined by the investigator's clinical judgment. The blinded treatment is continued. Two optional imaging sub-studies are included (ultrasound and contrast-media enhanced magnetic resonance angiography [MRA]) to assess vessel wall inflammation and occlusion before and after treatment. The primary endpoint is the proportion of patients in sustained remission until week 28 in the secukinumab group compared to the proportion of patients in the placebo group. A Bayesian approach is applied.

Discussion: The trial design allows the first placebo-controlled data collection on the efficacy and safety of secukinumab in patients with GCA.

Trial Registration: ClinicalTrials.gov NCT03765788 . Registration on 5 December 2018, prospective registration, EudraCT number 2018-002610-12; clinical trial protocol number CAIN457ADE11C.
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http://dx.doi.org/10.1186/s13063-021-05520-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8369438PMC
August 2021

Treat-to-target strategy with secukinumab as a first-line biological disease modifying anti-rheumatic drug compared to standard-of-care treatment in patients with active axial spondyloarthritis: protocol for a randomised open-label phase III study, AScalate.

BMJ Open 2020 09 30;10(9):e039059. Epub 2020 Sep 30.

Rheumazentrum Ruhrgebiet Herne, Ruhr-University Bochum, Bochum, Germany.

Introduction: In patients with axial spondyloarthritis (axSpA), biological disease-modifying anti-rheumatic drugs (bDMARDs) are recommended to those with inadequate response or contraindications to non-steroidal anti-inflammatory drugs (NSAIDs). In case of failure of the first bDMARD, a switch within the class or to other bDMARD is recommended. Despite these treatment options, there is no optimal treat-to-target (T2T) strategy. This study aims to evaluate the efficacy of a T2T strategy in patients with axSpA, with secukinumab as a first-line bDMARD, compared with standard-of-care (SOC) treatment.

Methods And Analyses: This is a randomised, parallel-group, open-label, multicentre ongoing study in patients with axSpA who are naïve to bDMARD and who have had an inadequate response to NSAIDs. The study will include an 8-week screening period, a 36-week treatment period and a 20-week safety follow-up period. At baseline, patients will be randomised (1:1) to T2T or SOC group. In the T2T group, patients will be treated with secukinumab 150 mg subcutaneous (s.c.) weekly until week 4 and then at week 8. For non-responders (patients without Ankylosing Spondylitis Disease Activity Score [ASDAS] clinically important improvement; change from baseline ≥1.1) at week 12, dose will be escalated to 300 mg s.c. every 4 weeks until week 24. Non-responders at week 24 will be switched to adalimumab biosimilar 40 mg s.c. every 2 weeks until week 34. In the SOC group, patients will receive treatment at the discretion of the physician. The primary endpoint is the proportion of patients achieving an Assessment in SpondyloArthritis International Society 40% (ASAS40) response at week 24.

Ethics And Dissemination: The study is being conducted as per the ethical principles of the Declaration of Helsinki and after approval from independent ethics committees/institutional review boards. The first results are expected to be published in early 2022.

Trial Registration Number: This study is registered with ClinicalTrials.gov, NCT03906136.
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http://dx.doi.org/10.1136/bmjopen-2020-039059DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7528363PMC
September 2020

Peptidase inhibitor 16 is a membrane-tethered regulator of chemerin processing in the myocardium.

J Mol Cell Cardiol 2016 Oct 15;99:57-64. Epub 2016 Aug 15.

Institute of Pharmacology and Toxicology, Technische Universität München, Biedersteiner Straße 29, 80802 Munich, Germany; DZHK (German Center for Cardiovascular Research) partner site Munich Heart Alliance, 80802 Munich, Germany. Electronic address:

A key response of the myocardium to stress is the secretion of factors with paracrine or endocrine function. Intriguing in this respect is peptidase inhibitor 16 (PI16), a member of the CAP family of proteins which we found to be highly upregulated in cardiac disease. Up to this point, the mechanism of action and physiological function of PI16 remained elusive. Here, we show that PI16 is predominantly expressed by cardiac fibroblasts, which expose PI16 to the interstitium via a glycophosphatidylinositol (-GPI) membrane anchor. Based on a reported genetic association of PI16 and plasma levels of the chemokine chemerin, we investigated whether PI16 regulates post-translational processing of its precursor pro-chemerin. PI16-deficient mice were engineered and found to generate higher levels of processed chemerin than wildtype mice. Purified recombinant PI16 efficiently inhibited cathepsin K, a chemerin-activating protease, in vitro. Moreover, we show that conditioned medium from PI16-overexpressing cells impaired the activation of pro-chemerin. Together, our data indicate that PI16 suppresses chemerin activation in the myocardium and suggest that this circuit may be part of the cardiac stress response.
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http://dx.doi.org/10.1016/j.yjmcc.2016.08.010DOI Listing
October 2016
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