eprintid: 10159391
rev_number: 11
eprint_status: archive
userid: 699
dir: disk0/10/15/93/91
datestamp: 2022-11-16 11:55:38
lastmod: 2023-10-30 11:06:04
status_changed: 2022-11-16 11:55:38
type: article
metadata_visibility: show
sword_depositor: 699
creators_name: Lorenzo-Vizcaya, Ana
creators_name: Isenberg, David Alan
title: Clinical trials in systemic lupus erythematosus: the dilemma—Why have phase III trials failed to confirm the promising results of phase II trials?
ispublished: pub
divisions: UCL
divisions: B02
divisions: C10
divisions: D17
note: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
abstract: Systemic lupus erythematosus (SLE) is an autoimmune rheumatic disease of unknown aetiology, characterised by the production of auto-antibodies and formation of immune complexes against self-antigens and complement activation. This inflammatory response can lead to tissue infiltration and eventually, to organ damage.Patients with SLE invariably have periods of relapse and remission. Flares can occur even when the patient is on seemingly adequate treatment, which suggests that more effective therapies are necessary for the management of SLE. Thus, trials with many drugs against different targets, such as CD22, IL-12 and IL-23 or tyrosine kinases, have been carried out in recent years.A frustrating feature of some of the biologic drugs used to treat SLE has been the reporting of successful phase II trials followed by failures of the phase III trials.In this review, we will focus on phase II and III trials carried out with epratuzumab (anti CD22), baricitinib (Janus kinases inhibitor), rigerimod (P140 peptide) and ustekinumab (IL-12 and IL-23 inhibitor) and consider the reasons for their ultimate failure to 'make the grade'. Likewise, we will try to explain the possible reasons that can influence why good results may be obtained in phase II trials and lead to undue optimism.
date: 2023-02
date_type: published
publisher: BMJ PUBLISHING GROUP
official_url: https://doi.org/10.1136/ard-2022-222839
oa_status: green
full_text_type: other
language: eng
primo: open
primo_central: open_green
verified: verified_manual
elements_id: 1981491
doi: 10.1136/ard-2022-222839
medium: Print-Electronic
pii: ard-2022-222839
lyricists_name: Isenberg, David
lyricists_id: DAISE40
actors_name: Isenberg, David
actors_name: Geary, Esther
actors_id: DAISE40
actors_id: ECGEA88
actors_role: owner
actors_role: impersonator
full_text_status: public
publication: Annals of the Rheumatic Diseases
volume: 82
number: 2
pagerange: 169-174
pages: 6
event_location: England
issn: 0003-4967
citation:        Lorenzo-Vizcaya, Ana;    Isenberg, David Alan;      (2023)    Clinical trials in systemic lupus erythematosus: the dilemma—Why have phase III trials failed to confirm the promising results of phase II trials?                   Annals of the Rheumatic Diseases , 82  (2)   pp. 169-174.    10.1136/ard-2022-222839 <https://doi.org/10.1136/ard-2022-222839>.       Green open access   
 
document_url: https://discovery.ucl.ac.uk/id/eprint/10159391/2/Isenberg_CLINICAL%20TRIALS%20IN%20SYSTEMIC%20LUPUS%20ERYTHEMATOSUS%20CLEAN%20COPY%2021.07.2022.pdf