Efficacy and safety of adjuvant immunoadsorption in pemphigus vulgaris and pemphigus foliaceus (IA-Pem Study): a multicentre randomised controlled trial.


Journal

The British journal of dermatology
ISSN: 1365-2133
Titre abrégé: Br J Dermatol
Pays: England
ID NLM: 0004041

Informations de publication

Date de publication:
22 Dec 2023
Historique:
received: 31 08 2023
revised: 23 11 2023
accepted: 21 12 2023
medline: 22 12 2023
pubmed: 22 12 2023
entrez: 22 12 2023
Statut: aheadofprint

Résumé

Pemphigus vulgaris (PV) and pemphigus foliaceus (PF) are potentially life-threatening autoimmune blistering diseases. Treatment is based on long term immunosuppression with high doses of glucocorticosteroids in combination with potentially corticosteroid-sparing agents and/or rituximab. Immunoadsorption (IA) has emerged as fast acting adjuvant treatment option. To assess the clinical efficacy of IA in addition to best medical treatment. Multicentre (26 centres from Germany and Austria) randomised controlled trial in 72 patients with newly diagnosed, relapsed or chronic active PV or PF (34 females, 38 males, aged 42-72 years) comparing best medical treatment (BMT) (prednisolone 1.0 mg/kg/d plus azathioprine or mycophenolate) to adjuvant IA (BMT+IA). Central 1:1 randomization was done at the coordinating centre for clinical trials (KKS) Marburg. The primary endpoint was analyzed using Kaplan-Meier and Cox regression methods. The study was ended prematurely due to safety concerns after random allocation of 72 patients to BMT+IA (n=34) or BMT (n=38). The primary endpoint, time to complete remission on therapy, was not significantly different between the groups (p=0.39; HR 1.35 (95%CI: 0.68-2.69). The cumulative dose of prednisolone was significantly lower in the BMT+IA compared to BMT alone (difference -1,214; 95%CI, -2,225 - -70; p=0.03). In a post hoc analysis, patients with more extensive PV/PF showed a tendency towards a shorter time to remission in the BMT+IA group compared to the BMT group (HR=1.87, p=0.17 in patients with baseline PDAI ≥ 15). While more adverse events were observed in patients of the BMT group (29 vs. 25), severe adverse events were more frequent in patients of the BMT+IA group (17 events in 10 patients vs. 11 events in 8 patients). In this study, adjuvant IA did not show a shorter time to clinical remission but a corticosteroid-sparing effect. In patients with extensive PV/PF, post hoc analysis suggests that adjuvant IA may possibly lead to earlier remission, but potential adverse events must be carefully weighed against the expected benefits.

Sections du résumé

BACKGROUND BACKGROUND
Pemphigus vulgaris (PV) and pemphigus foliaceus (PF) are potentially life-threatening autoimmune blistering diseases. Treatment is based on long term immunosuppression with high doses of glucocorticosteroids in combination with potentially corticosteroid-sparing agents and/or rituximab. Immunoadsorption (IA) has emerged as fast acting adjuvant treatment option.
OBJECTIVES OBJECTIVE
To assess the clinical efficacy of IA in addition to best medical treatment.
METHODS METHODS
Multicentre (26 centres from Germany and Austria) randomised controlled trial in 72 patients with newly diagnosed, relapsed or chronic active PV or PF (34 females, 38 males, aged 42-72 years) comparing best medical treatment (BMT) (prednisolone 1.0 mg/kg/d plus azathioprine or mycophenolate) to adjuvant IA (BMT+IA). Central 1:1 randomization was done at the coordinating centre for clinical trials (KKS) Marburg. The primary endpoint was analyzed using Kaplan-Meier and Cox regression methods.
RESULTS RESULTS
The study was ended prematurely due to safety concerns after random allocation of 72 patients to BMT+IA (n=34) or BMT (n=38). The primary endpoint, time to complete remission on therapy, was not significantly different between the groups (p=0.39; HR 1.35 (95%CI: 0.68-2.69). The cumulative dose of prednisolone was significantly lower in the BMT+IA compared to BMT alone (difference -1,214; 95%CI, -2,225 - -70; p=0.03). In a post hoc analysis, patients with more extensive PV/PF showed a tendency towards a shorter time to remission in the BMT+IA group compared to the BMT group (HR=1.87, p=0.17 in patients with baseline PDAI ≥ 15). While more adverse events were observed in patients of the BMT group (29 vs. 25), severe adverse events were more frequent in patients of the BMT+IA group (17 events in 10 patients vs. 11 events in 8 patients).
CONCLUSIONS CONCLUSIONS
In this study, adjuvant IA did not show a shorter time to clinical remission but a corticosteroid-sparing effect. In patients with extensive PV/PF, post hoc analysis suggests that adjuvant IA may possibly lead to earlier remission, but potential adverse events must be carefully weighed against the expected benefits.

Identifiants

pubmed: 38133541
pii: 7491160
doi: 10.1093/bjd/ljad489
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

© The Author(s) 2023. Published by Oxford University Press on behalf of British Association of Dermatologists.

Auteurs

Nina van Beek (N)

Department of Dermatology, Allergology and Venereology, University of Lübeck, Lübeck, Germany.

Rüdiger Eming (R)

Department of Dermatology and Allergology, Phillips University, Marburg, Germany.

Alexander Reuss (A)

Coordinating Center for Clinical Trials, Phillips University, Marburg, Germany.

Detlef Zillikens (D)

Department of Dermatology, Allergology and Venereology, University of Lübeck, Lübeck, Germany.

Miklós Sárdy (M)

Department of Dermatology and Allergy, University Hospital, LMU Munich, Munich, Germany.

Claudia Günther (C)

Department of Dermatology, University Hospital Carl Gustav Carus, TU Dresden, Dresden, Germany.

Dimitra Kiritsi (D)

Department of Dermatology and Venereology, University Hospital Freiburg, Freiburg, Germany.

Sandrine Benoit (S)

Department of Dermatology, Venereology and Allergology, University Hospital Würzburg, Würzburg, Germany.

Stefan Beissert (S)

Department of Dermatology, University Hospital Carl Gustav Carus, TU Dresden, Dresden, Germany.

Regine Gläser (R)

Department of Dermatology, Venereology and Allergology, Christian-Albrechts University, Kiel, Germany.

Harald Gollnick (H)

Department of Dermatology and Venereology, Otto-von-Guericke University, Magdeburg, Germany.

Orsolya N Horváth (ON)

Department of Dermatology and Allergy, University Hospital, LMU Munich, Munich, Germany.

Christiane Pfeiffer (C)

Department of Dermatology and Allergology, University Hospital Ulm, Ulm, Germany.

Martin Röcken (M)

Department of Dermatology, Eberhard Karls University, Tübingen, Germany.

Franziska Schauer (F)

Department of Dermatology and Venereology, University Hospital Freiburg, Freiburg, Germany.

Stephan Schreml (S)

Department of Dermatology, University Medical Centre Regensburg, Regensburg, Germany.

Kerstin Steinbrink (K)

Department of Dermatology, Johannes-Gutenberg University Mainz, Mainz, Germany.

Alexander Zink (A)

Department of Dermatology and Allergology, Technical University Munich, Munich, Germany.

Carmen Schade-Brittinger (C)

Coordinating Center for Clinical Trials, Phillips University, Marburg, Germany.

Michael Hertl (M)

Department of Dermatology and Allergology, Phillips University, Marburg, Germany.

Enno Schmidt (E)

Department of Dermatology, Allergology and Venereology, University of Lübeck, Lübeck, Germany.
Lübeck Institute of Experimental Dermatology, University of Lübeck, Lübeck, Germany.

Classifications MeSH