eprintid: 10073189
rev_number: 23
eprint_status: archive
userid: 608
dir: disk0/10/07/31/89
datestamp: 2019-05-07 13:23:02
lastmod: 2021-09-23 22:53:58
status_changed: 2019-05-07 13:23:02
type: article
metadata_visibility: show
creators_name: Neave, L
creators_name: Gale, DP
creators_name: Cheesman, S
creators_name: Shah, R
creators_name: Scully, M
title: Atypical haemolytic uraemic syndrome in the eculizumab era: presentation, response to treatment and evaluation of an eculizumab withdrawal strategy
ispublished: pub
subjects: UCH
divisions: UCL
divisions: B02
divisions: C10
divisions: D17
divisions: G93
keywords: aHUS, TMA, atypical haemolytic uraemic syndrome, eculizumab, withdrawal
note: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
abstract: The complement inhibitor, eculizumab, has revolutionised the management of atypical haemolytic uraemic syndrome (aHUS), although the optimum treatment duration is debated. Twenty-two cases of acute aHUS managed with eculizumab were retrospectively reviewed, including outcomes after eculizumab withdrawal. Although 41% had an associated complement genetic abnormality, mutation status did not affect severity of clinical presentation. Sixty-four percent required renal replacement acutely, with a high incidence of nephrotic range proteinuria (47%). Eculizumab followed a median of 6 days of plasma exchange. After a median duration of therapy of 11 weeks (range 1-227), haematological recovery was seen in 100%, while 81% achieved at least partial renal recovery (median increase in estimated glomerular filtration rate (eGFR) 49 ml/min/1·73 m2 ). At median duration of follow-up of 85 weeks (range 4-255), 54·5% had eGFR ≥ 60 ml/min/1·73 m2 , 27% had CKD, 14% were on dialysis, and 4·5% had died. Eculizumab was withdrawn in 59% (13/22) cases following complete haematological and renal recovery. Three of these 13 patients (23%) subsequently relapsed, with defined triggers in 2/3, but all made a full recovery with rapid resumption of eculizumab. There was a significant association between higher presenting creatinine and poorer renal outcomes. A strategy of eculizumab withdrawal in selected cases is both safe and cost effective.
date: 2019-07
date_type: published
official_url: https://doi.org/10.1111/bjh.15899
oa_status: green
full_text_type: other
language: eng
primo: open
primo_central: open_green
verified: verified_manual
elements_id: 1645189
doi: 10.1111/bjh.15899
lyricists_name: Gale, Daniel
lyricists_id: DGALE18
actors_name: Gale, Daniel
actors_id: DGALE18
actors_role: owner
full_text_status: public
publication: British Journal of Haematology
volume: 186
number: 1
pagerange: 113-124
issn: 0007-1048
citation:        Neave, L;    Gale, DP;    Cheesman, S;    Shah, R;    Scully, M;      (2019)    Atypical haemolytic uraemic syndrome in the eculizumab era: presentation, response to treatment and evaluation of an eculizumab withdrawal strategy.                   British Journal of Haematology , 186  (1)   pp. 113-124.    10.1111/bjh.15899 <https://doi.org/10.1111/bjh.15899>.       Green open access   
 
document_url: https://discovery.ucl.ac.uk/id/eprint/10073189/1/2019%20Neave%20et%20al%20aHUS%20and%20Eculizumab%20withdrawal%20BJH%202019.pdf