High-Grade Salivary-Gland Involvement, Assessed by Histology or Ultrasonography, Is Associated with a Poor Response to a Single Rituximab Course in Primary Sjögren's Syndrome: Data from the TEARS Randomized Trial.
OBJECTIVE
To determine whether the severity of salivary-gland involvement, assessed using salivary gland ultrasonography [SGUS], histological focus score, or the unstimulated whole salivary flow [UWSF], was associated with the response to rituximab in patients with primary Sjögren's syndrome [pSS].


METHODS
Among the 120 patients with pSS enrolled in the randomised TEARS trial of rituximab versus placebo, 35 underwent either centralised minor salivary-gland biopsy or SGUS at inclusion. The echostructure of each parotid and submandibular gland was graded on a scale of 0 to 4. Histologic minor salivary gland involvement was assessed by the focus score. Among rituximab-treated patients with available data (n = 14), half met the Sjögren's Syndrome Responder Index [SSRI]-30 definition of a response at week 24.


RESULTS
The SGUS score correlated positively to the focus score [r = 0.61] and negatively to the UWSF [r = -0.68]. The focus score was not correlated to the UWSF. The median total SGUS grade at inclusion was 9 [6-11] in responders versus 16 [11-16] in non-responders [p = 0.04]. The proportion of SSRI-30 responders was 0% among patients with SGUS grade 4 and 88% among those with SGUS grade ≤3. Low baseline SGUS scores were associated with sicca-related outcomes improvement, but not with fatigue or biological improvement. Median baseline focus score was 0.3 [0.0-1.3] in the responders versus 4.0 [2.7-5.3] in the non-responders [p = 0.02]. Baseline UWSF was not associated with the response rate.


CONCLUSIONS
In patients with pSS, the highest SGUS grade or a high histological focus score is associated with absence of a response to a single rituximab course after 6 months. Further studies, including more patients and different treatment strategies, are required to confirm the clinical utility of these potential biomarkers in pSS.
Service de Rhumatologie, Hôpital de la Cavale Blanche, CHRU Brest, Boulevard Tanguy Prigent, 29609 Brest, France.|EA2216, INSERM ESPRI, ERI29, Laboratoire d'Immunothérapies et Pathologies lymphocytaires B, Université de Brest, and Labex "IGO", Brest, France.
Divi
D
Cornec
Service de Rhumatologie, Hôpital de la Cavale Blanche, CHRU Brest, Boulevard Tanguy Prigent, 29609 Brest, France.|EA2216, INSERM ESPRI, ERI29, Laboratoire d'Immunothérapies et Pathologies lymphocytaires B, Université de Brest, and Labex "IGO", Brest, France.
Sandrine
S
Jousse-Joulin
Laboratoire d'Anatomie Pathologique et Cytologie, Hôpital Morvan, CHRU Brest, Avenue Foch, 29609 Brest, France.
Sebastian
S
Costa
Service de Rhumatologie, Hôpital de la Cavale Blanche, CHRU Brest, Boulevard Tanguy Prigent, 29609 Brest, France.
Thierry
T
Marhadour
Laboratoire d'Anatomie Pathologique et Cytologie, Hôpital Morvan, CHRU Brest, Avenue Foch, 29609 Brest, France.
Pascale
P
Marcorelles
Service de Rhumatologie, Hôtel-Dieu, CHU Nantes, 44093 Nantes Cedex 01, France.
Jean-Marie
JM
Berthelot
Service de Médecine Interne, Claude Huriez Hospital, Université Lille Nord-de-France, 59037 Lille Cedex, France.
Eric
E
Hachulla
Service de Médecine Interne, Claude Huriez Hospital, Université Lille Nord-de-France, 59037 Lille Cedex, France.
Pierre-Yves
PY
Hatron
Service de Rhumatologie, CHRU de Rouen, 76230 Bois-Guillaume, France.
Vincent
V
Goeb
Service de Rhumatologie, CHRU de Rouen, 76230 Bois-Guillaume, France.
Olivier
O
Vittecoq
INSERM CIC 0502, CHU Brest, Brest, France.
Emmanuel
E
Nowak
EA2216, INSERM ESPRI, ERI29, Laboratoire d'Immunothérapies et Pathologies lymphocytaires B, Université de Brest, and Labex "IGO", Brest, France.
Jacques-Olivier
JO
Pers
Service de Rhumatologie, Hôpital de la Cavale Blanche, CHRU Brest, Boulevard Tanguy Prigent, 29609 Brest, France.|EA2216, INSERM ESPRI, ERI29, Laboratoire d'Immunothérapies et Pathologies lymphocytaires B, Université de Brest, and Labex "IGO", Brest, France.
Valérie
V
Devauchelle-Pensec
Service de Rhumatologie, Hôpital de la Cavale Blanche, CHRU Brest, Boulevard Tanguy Prigent, 29609 Brest, France.|EA2216, INSERM ESPRI, ERI29, Laboratoire d'Immunothérapies et Pathologies lymphocytaires B, Université de Brest, and Labex "IGO", Brest, France.
Alain
A
Saraux
Rheumatology (Oxford). 2016 May;55(5):789-800
26667216
Ultrasound Med Biol. 2016 Mar;42(3):645-53
26715188
Ann Rheum Dis. 2015 Sep;74(9):1645-50
26034044
Ann Rheum Dis. 2014 Aug;73(8):1537-40
24525912
Arthritis Rheum. 2004 Jul;50(7):2240-5
15248223
Rev Med Interne. 2016 Mar;37(3):186-94
26608250
Arthritis Rheum. 2004 Apr;50(4):1270-6
15077311
BMC Musculoskelet Disord. 2014 Jan 17;15:21
24438039
Ann Rheum Dis. 2015 Mar;74(3):e25
25381229
JAMA. 2014 Jul 16;312(3):249-58
25027140
Joint Bone Spine. 2016 May;83(3):301-6
26678002
Ann Rheum Dis. 2002 Jun;61(6):554-8
12006334
Acta Odontol Scand. 2004 Oct;62(5):264-8
15841813
Rheumatology (Oxford). 2015 Jun;54(6):1056-64
25433039
Arthritis Res Ther. 2015 May 28;17 :146
26022533
Arthritis Rheum. 2013 Jan;65(1):216-25
23108632
Arthritis Res Ther. 2016 Jan 20;18:21
26785742
Rheumatology (Oxford). 2014 Sep;53(9):1604-7
24706989
Semin Arthritis Rheum. 2014 Dec;44(3):314-24
24935529
Clin Exp Rheumatol. 2015 Jan-Feb;33(1):56-62
25535773
J Autoimmun. 2016 Feb;67:102-10
26688003
J Autoimmun. 2012 Sep;39(3):161-7
22749831
Arthritis Rheum. 2005 Sep;52(9):2740-50
16142737
Arthritis Rheum. 1984 Feb;27(2):147-56
6696772
Oral Dis. 2015 Sep;21(6):792-800
25988616
Ann Rheum Dis. 2016 Jun;75(6):e33
26895746
Ann Rheum Dis. 2016 Nov;75(11):1933-1938
26757748
Eur Radiol. 2015 Oct;25(10 ):3027-34
25861884
Ann Intern Med. 2014 Feb 18;160(4):233-42
24727841
Arthritis Rheumatol. 2015 Jun;67(6):1623-8
25708147
Rheumatology (Oxford). 2007 Feb;46(2):335-41
16891656
Ann Rheum Dis. 2007 Jan;66(1):107-12
16728458
Rheumatology (Oxford). 2014 Nov;53(11):1977-83
24907148
Ann Rheum Dis. 2016 Jun;75(6):e34
26961295
Rheumatology (Oxford). 2015 Sep;54(9):1699-708
25957440
Rheumatology (Oxford). 2015 Jan;54(1):199-200
25288782
Arthritis Care Res (Hoboken). 2014 Jul;66(7):1102-7
24339361
Arthritis Rheum. 2007 Mar 15;57(2):310-7
17330280