Efficacy and safety of rituximab-based treatments in angioedema with acquired C1 inhibitor deficiency.
Galith Kalmi
(1)
,
Yann Nguyen
(2)
,
Stephanie Amarger
(3)
,
Magali Aubineau
(4)
,
Beatrice Bibes
(5)
,
Claire Blanchard-Delaunay
(6)
,
Isabelle Boccon-Gibod
(7)
,
Laurence Bouillet
(8, 7)
,
Paul Coppo
(1)
,
Marie-Caroline Dalmas
(9)
,
Sophie Debord-Peguet
(4)
,
Federica Defendi
(8)
,
Claire Demoreuil
(10)
,
Aurélie Du-Thanh
(11)
,
Stephanie Gayet
(12)
,
Jérôme Hadjadj
(1)
,
Pierre-Yves Jeandel
(13)
,
David Launay
(14)
,
Kim Heang Ly
(15)
,
Chloé Mc Avoy
(1)
,
Mathilde Niault
(16)
,
Yann Ollivier
(17, 1)
,
Fabien Pelletier
(18)
,
Marc Porneuf
(19)
,
Damien Roos-Weil
(19)
,
Olivier Fain
(1)
,
Delphine Gobert
(1)
1
CHU Saint-Antoine [AP-HP]
2 Hôpital Beaujon [AP-HP]
3 CHU Gabriel Montpied [Clermont-Ferrand]
4 HCL - Hospices Civils de Lyon
5 Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Pontchaillou]
6 CH Georges Renon Niort - Centre Hospitalier Georges Renon [Niort]
7 CREAK - Centre de référence national des angiœdèmes
8 CHUGA - Centre Hospitalier Universitaire [CHU Grenoble]
9 CHU Strasbourg - Centre Hospitalier Universitaire [Strasbourg]
10 CHU - BREST - Hôpital de la Cavale Blanche - CHRU Brest
11 CHRU Montpellier - Centre Hospitalier Régional Universitaire [Montpellier]
12 TIMONE - Hôpital de la Timone [CHU - APHM]
13 CHU Nice - Centre Hospitalier Universitaire de Nice
14 LIRIC - Lille Inflammation Research International Center - U 995
15 CHU Limoges
16 GHBS - Groupe Hospitalier Bretagne Sud
17 CHU Caen
18 CHRU Besançon - Centre Hospitalier Régional Universitaire de Besançon
19 CH Saint-Brieuc - Centre hospitalier de Saint-Brieuc [Hôpital Yves Le Foll]
2 Hôpital Beaujon [AP-HP]
3 CHU Gabriel Montpied [Clermont-Ferrand]
4 HCL - Hospices Civils de Lyon
5 Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Pontchaillou]
6 CH Georges Renon Niort - Centre Hospitalier Georges Renon [Niort]
7 CREAK - Centre de référence national des angiœdèmes
8 CHUGA - Centre Hospitalier Universitaire [CHU Grenoble]
9 CHU Strasbourg - Centre Hospitalier Universitaire [Strasbourg]
10 CHU - BREST - Hôpital de la Cavale Blanche - CHRU Brest
11 CHRU Montpellier - Centre Hospitalier Régional Universitaire [Montpellier]
12 TIMONE - Hôpital de la Timone [CHU - APHM]
13 CHU Nice - Centre Hospitalier Universitaire de Nice
14 LIRIC - Lille Inflammation Research International Center - U 995
15 CHU Limoges
16 GHBS - Groupe Hospitalier Bretagne Sud
17 CHU Caen
18 CHRU Besançon - Centre Hospitalier Régional Universitaire de Besançon
19 CH Saint-Brieuc - Centre hospitalier de Saint-Brieuc [Hôpital Yves Le Foll]
Résumé
Angioedema (AE) due to acquired C1-inhibitor (C1-INH) deficiency (AAE–C1-INH) is related to excessive consumption of C1-INH or to anti–C1-INH antibodies, and is frequently associated with lymphoproliferative syndromes or monoclonal gammopathies. Standard of care for prophylactic treatment in this condition is not established. Rituximab may be effective to prevent attacks, especially if the lymphoid hemopathy is controlled, but data are scarce.
Objective
To evaluate efficacy of rituximab in AAE–C1-INH.
Methods
A retrospective multicenter study was carried out in France, including patients with AAE–C1-INH treated with rituximab between April 2005 and July 2019.
Results
Fifty-five patients with AAE–C1-INH were included in the study, and 23 of them had an anti–C1-INH antibody. A lymphoid malignancy was identified in 39 patients, and a monoclonal gammopathy in 9. There was no associated condition in 7 cases. Thirty patients received rituximab alone or in association with chemotherapy (n = 25). Among 51 patients with available follow-up, 34 patients were in clinical remission and 17 patients had active AE after a median follow-up of 3.9 years (interquartile range, 1.5-7.7). Three patients died. The presence of anti–C1-INH antibodies was associated with a lower probability of AE remission (hazard ratio, 0.29 [95% CI, 0.12-0.67]; P = .004). Relapse was less frequent in patients with lymphoma (risk ratio, 0.27 [95% CI, 0.09-0.80]; P = .019) and in patients treated with rituximab and chemotherapy (risk ratio, 0.31 [95% CI, 0.12-0.79]; P = .014).
Conclusions
Rituximab is an efficient and well-tolerated therapeutic option in AE, especially in lymphoid malignancies and in the absence of detectable anti–C1-INH antibodies.