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com

Clinical and epidemiological research

CONCISE REPORT

Efficacy of rituximab in systemic manifestations

of primary Sjögren’s syndrome: results in 78 patients
of the AutoImmune and Rituximab registry
Jacques-Eric Gottenberg,1 Gael Cinquetti,2 Claire Larroche,3 Bernard Combe,4
Eric Hachulla,5 Olivier Meyer,6 Edouard Pertuiset,7 Guy Kaplanski,8 Laurent Chiche,8
Jean-Marie Berthelot,9 Bruno Gombert,10 Philippe Goupille,11 Christian Marcelli,12
Séverine Feuillet,13 Jean Leone,14 Jean Sibilia,1 Charles Zarnitsky,15 Philippe Carli,16
Stephanie Rist,17 Philippe Gaudin,18 Carine Salliot,17 Muriel Piperno,19
Adeline Deplas,20 Maxime Breban,21 Thierry Lequerre,22 Pascal Richette,23
Charles Ghiringhelli,24 Mohamed Hamidou,25 Philippe Ravaud,26 Xavier Mariette,27 for
the Club Rhumatismes et Inflammations and the French Society of Rheumatology

For numbered affiliations see
end of article.
Correspondence to
Professor
Jacques-Eric Gottenberg,
ImmunoRhumatologie
Moléculaire, Service de
Rhumatologie, INSERM
UMR_S 1109, Université de
Strasbourg, Centre National de
Référence des Maladies
Auto-Immunes, Hôpital
Hautepierre, 1 Avenue Molière,
67000 Strasbourg 67098,
France; jacques-eric.
gottenberg@chru-strasbourg.fr
J-EG and GC contributed
equally to this study.
Received 2 July 2012
Revised 12 October 2012
Accepted 18 November 2012
Published Online First
21 December 2012
ABSTRACT
Objectives To evaluate the efficacy and safety of
rituximab in patients with primary Sjögren’s syndrome
( pSS).
Methods The AutoImmune and Rituximab registry has
included 86 patients with pSS treated with rituximab,
prospectivey followed up every 6 months for 5 years.
Results Seventy-eight patients with pSS (11 men,
67 women), who already had at least one follow-up visit,
were analysed. Median age was 59.8 years (29–83),
median duration of disease was 11.9 years (3–32).
Indications for treatment were systemic involvement for
74 patients and only severe glandular involvement in four
patients. The median European Sjögren’s Syndrome
disease activity index (ESSDAI) was 11 (2–31).
17 patients were concomitantly treated with another
immunosuppressant agent. Median follow-up was
34.9 months (6–81.4) (226 patient-years). Overall efficacy
according to the treating physician was observed in
47 patients (60%) after the first cycle of rituximab.
Median ESSDAI decreased from 11 (2–31) to 7.5 (0–26)
( p<0.0001). Median dosage of corticosteroid decreased
from 17.6 mg/day (3–60) to 10.8 mg/day ( p=0.1).
Forty-one patients were retreated with rituximab. Four
infusion reactions and one delayed serum sickness-like
disease resulted in rituximab discontinuation. Three
serious infections (1.3/100 patient-years) and two
cancer-related deaths occurred.
Conclusions In common practice, the use of rituximab
in pSS is mostly restricted to patients with systemic
involvement. This prospective study shows good efficacy
and tolerance of rituximab in patients with pSS and
systemic involvement.
INTRODUCTION
Primary Sjögren’s syndrome ( pSS) is a systemic
autoimmune disease that is characterised in the
majority of patients by dryness, fatigue and pain.
Systemic manifestations occur in 20–40% of
patients.1 2
B lymphocytes play a crucial role in pathogenesis
of the disease by their capacity to secrete autoanti-
bodies and cytokines or present autoantigens.3 4
Evidence-based therapy for pSS is largely limited to
symptomatic treatments that improve dryness.3
Some efficacy of rituximab, an anti-CD20 mono-
clonal antibody, was suggested in case reports,
retrospective or open studies and in two controlled
trials.5 6 However, only very few of the reported
patients had been treated with rituximab for sys-
temic complications other than lymphoma.
Rituximab is currently not labelled for pSS and no
information is available concerning its use in
common practice.
We therefore evaluated the indications, efficacy
and safety of rituximab in pSS, using the prospect-
ive data of the AutoImmune and Rituximab (AIR)
registry.
PATIENTS AND METHODS
Patients
AIR is an independent multicentre registry pro-
moted by the French Society of Rheumatology and
the Club Rhumatismes et Inflammation, which
includes patients treated with rituximab for refrac-
tory autoimmune diseases, including rheumatoid
arthritis (RA), pSS according to the European
American consensus group criteria, systemic lupus
erythematosus (SLE), myositis, vasculitis and other
refractory autoimmune diseases. A total of 3662
patients has been included and prospectively fol-
lowed up.7
Data were collected at baseline, 3 and 6-month
follow-up and then every 6 months. This study
was approved by the French authorities (Comité
Consultatif sur le Traitement de l’information en
matière de Recherche dans le domaine de la Santé
and Commission Nationale de l’Informatique et
des Libertés). Written informed consent was
obtained from all patients.
The only parameter that was not prospectively
collected by each investigator was the European

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Clinical and epidemiological research

Sjögren’s syndrome disease activity index (ESSDAI),4 which did Table 1 Characteristics of the 78 patients with pSS enrolled in the
not exist when the electronic case report form (e-CRF) was AIR registry
created, and was retrospectively calculated before and after Clinical data
rituximab. The ESSDAI is a consensus clinical index set up by
a European League Against Rheumatism task force and Age, years 59.8 (29–83)
designed to measure systemic disease activity in patients with Sex, women 67 (86%)
pSS through 12 different organ-specific domains of Disease duration, years 11.9 (3–32)
involvement. Laboratory data
Efficacy was assessed 6 months after the first cycle of rituxi- No anti-SSA 24 (31%)
mab according to the global opinion of the physician. Each sys- Anti-SSA alone 34 (44%)
temic complication was evaluated by objective tests if possible. Anti-SSA+anti-SSB 20 (25%)
A summary of each chart (adverse events, efficacy) was validated Rituximab regimen
by the treating physician. Serious adverse events were validated 1 g×2, n (%) 67 (86%)
using chart copies by the two coordinators of the registry (XM 375 mg/m2×4, n (%) 11 (14%)
and JEG). Previous treatments
Corticosteroids 66 (85%)
Statistical analysis Hydroxychloroquine 44 (56%)
Data were presented as medians (ranges) for continuous vari- Methotrexate 33 (42%)
ables and numbers ( percentages) for qualitative variables. The Azathioprine 19 (24%)
non-parametric Mann–Whitney U test was used for continuous Leflunomide 8 (10%)
variables and Fisher’s exact test was used to compare qualita- Intravenous immunoglobulin 3 (4%)
tive variables. Statistical analyses were realised using GraphPad Plasmatic exchanges 3 (4%)
Prism software. A p value less than 0.05 was considered statis- Concomitant immunosuppressants
tically significant. Corticosteroids 7 (9%)
Hydroxychloroquine 7 (9%)
RESULTS Methotrexate 7 (9%)
Patient characteristics Azathioprine 1 (1%)
Among the 86 patients with pSS enrolled in the AIR registry, Mycophenolate mofetil 1 (1%)
78, who already had at least one follow-up visit at 6 months, Cyclophosphamide 1 (1%)
were analysed. Results are expressed as n (%).
The median age was 59.8 years (29–83), median duration of AIR, AutoImmune and Rituximab registry; pSS, primary Sjögren’s syndrome.
pSS was 11.9 years (3–32). Twenty-four patients (30.8%) had
no autoantibody, 54 (69.2%) were anti-SSA positive and
20 (25.6%) were anti-SSA and anti-SSB positive.
Previous treatments included corticosteroids in 66 patients, Six patients (8%) had renal involvement (one tubular acidosis
hydroxychloroquine in 44, methotrexate in 33, azathioprine in and five interstitial biopsy-confirmed interstitial nephritis).
19, mycophénolate mofetil in four, leflunomide in eight, intra- Three patients had myositis (elevated creatine-phosphokinase
venous immunoglobulins and plasmatic exchanges in three approximately twofold over the upper limit of normal, myogen
patients each. The main baseline characteristics of patients are features at electroneuromyography and histological myositis).
detailed in table 1. Two patients had autoimmune cytopaenias: one autoimmune
anaemia (haemoglobin concentration of 8 g/dl with positive
Indications for rituximab Coombs test) and one autoimmune thrombocytopaenia ( plate-
Seventy-four patients (95%) were prescribed rituximab for sys- let count: 30 giga/l). One patient had pSS-related autoimmune
temic involvement (32 patients for one main systemic complica- pancreatitis (serum lipase threefold over the lower limit of
tion, 42 patients for multiple systemic complications) (table 2). normal) despite corticosteroids and had normal serum levels of
Twenty-seven patients predominantly had articular involvement IgG4.
(only arthralgias in eight, synovitis in 19), six had pSS-related Four patients with only severe glandular involvement were
central nervous system (CNS) involvement with brain diffuse prescribed rituximab: two with parotid swelling and one with
white matter MRI abnormalities. Central neurological features lachrymal gland hypertrophy, previously refractory to corticos-
were progressive multiple sclerosis-like manifestations (n=4), teroids, and one sclera vasculitis and corneal perforation.
transverse myelitis (n=1), anxiety and depression disorder
(n=1) evidenced by neuropsychological testing. Twelve patients Rituximab regimen and comedications
had peripheral nervous system (PNS) involvement defined by The rituximab regimen is indicated in table 1. All patients
the presence of clinical signs of peripheral neuropathy confirmed received standard premedication with antihistamine, paraceta-
by electroneuromyography. Eight patients had pSS-related vas- mol and 100 mg methylprednisolone. Sixty-seven patients were
culitis: five cryoglobulinaemias with purpura and articular, PNS, initially treated with two rituximab infusions of 1 g, 11
renal involvement and three biopsy-confirmed small vessel patients with four infusions of 375 mg/m2. Corticosteroids
lymphoid vasculitis without any evidence of cryoglobulinaemia. were associated with rituximab in 29 patients with a median
Patients with neurological involvement or cryoglobulinaemia dosage of 17.6 mg/day (5–60). Other concomitant immunosup-
were previously reported (table 3). Nine patients had pSS-related pressant agents included methotrexate in seven patients, hydro-
pulmonary involvement: one bronchial involvement with xychloroquine in seven, azathioprine, mycophenolate mofetil
altered respiratory function tests, eight interstitial lung diseases and cyclophosphamide in one patient each. Sixty-one patients
(lung CT abnormalities in all patients) including one with (78%) received rituximab without any concomitant immuno-
lymphocytic alveolitis evidenced by broncho-alveolar lavage). suppressant other than corticosteroids.

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Clinical and epidemiological research
Table 2 Efficacy of rituximab on the various predominant organ involvements
Before rituximab
Systemic organ involvement
Articular
Nervous system
CNS
Multiple sclerosis-like manifestations
Transverse myelitis
Anxiety/depression
PNS
Mixed sensorimotor polyneuropathy
Sensory painful neuropathy (including sensory ataxic neuropathy)
Mononeuritis multiplex
Pulmonary
Vasculitis
Renal
Muscular
Haematological
Autoimmune pancreatitis
Glandular involvement
Hypertrophy of lachrymal glands
Sclera vasculitis
parotid hypertrophy
ESSDAI before rituximab (n=72)
Corticosteroids (mg/day) (n=29)
Results are expressed as n (%).
CNS, central nervous system; ESSDAI, European Sjögren’s syndrome disease activity index; PNS, peripheral nervous system.
Efficacy
The median follow-up was 34.9 months (6–81.4) (226 -
patient-years). Overall efficacy 6 months after the first cycle
after rituximab, assessed by the global opinion of the physician,
was observed in 47 patients (60%).
No data were available regarding the evolution of dryness,
pain and fatigue. Efficacy regarding each involvement is sum-
marised in table 2. Efficacy was observed in 45/74 patients
(61%) with systemic involvement. Efficacy was observed in
two out of four patients (50%) with only glandular involve-
ment (two parotid swellings). Parotid swelling was also
improved in two out of four patients (50%) with parotid swel-
ling associated with systemic involvement. Regarding articular
involvement, the median tender and swollen joint count
decreased from 9 to 0 ( p=0.003) and 4 to 0 ( p=0.004), respect-
ively, among the 17 patients with available data. The two
patients with autoimmune cytopaenia respectively normalised
their haemoglobin level (from 8 to 11 g/dl) and their platelet
count (from 30 to 153 giga/l). Among the patients with pul-
monary involvement, the patient with bronchial involvement
and six of the eight patients with interstitial disease responded
to the first cycle of rituximab according to their physician. All
the responder patients with interstitial lung disease were
retreated (two to nine cycles). Median ESSDAI, which could be
evaluated in 72 patients, decreased from 11 (2–31) before rituxi-
mab to 7.5 (0–26) 6 months after rituximab ( p<0.0001). A
decrease equal or greater than 20% and 30% of the initial
ESSDAI was observed, respectively, in 29 (69%) and 23 (55%)
of the 42 responders with systemic features and evaluated
ESSDAI.
In the 29 patients initially treated with corticosteroids, the
dose of corticosteroids 6 months after the first cycle of rituxi-
mab had increased in five, was stable in eight and decreased in
16 patients (discontinuation of corticosteroids in six and
1028
After rituximab
74 Systemic efficacy 44 (59%)
27 17 (63%)
18 8 (44%)
6 2 (33%)
4 0
1 1
1 1
12 6 (50%)
6 3
4 2
2 1
9 7 (78%)
8 5 (62.5%)
6 5 (83.3%)
3 0 (0%)
2 2 (100%)
1 1 (100%)
4 Glandular efficacy 2 (50%)
1 0
1 0
2 2
11.0 (2–31) ESSDAI after rituximab (n=72) 7.5 (0–26)
17.6 Corticosteroids after rituximab (n=23) 10.8
decrease in 10 patients) with the following involvements:
articular, four; pulmonary, three; renal, one; PNS, two; CNS,
one; vasculitis, two; myositis, one; autoimmune thrombocyto-
paenia, one; autoimmune pancreatitis, one. The median daily
dose of prednisone decreased from 17.6 to 10.8 mg, 6 months
after rituximab ( p=0.1). No significant difference in efficacy
was observed between patients without (65.2%) or with
anti-SSA/SSB antibodies (54.5%, p=0.5), or in patients treated
without (56.5%) or with concomitant immunosuppressant
agents other than corticosteroids (62.5%, p=0.9).
Tolerance
Five (6.4%) serious infusion reactions occurred. Four of them
were immediate infusion reactions (urticarial allergic reaction
with shock (one patient, first infusion), Quincke oedema (two
patients, first and second infusion), skin rash without fever or
synovitis (one patient, second infusion of the third cycle)
occurred. The latter was a delayed serum sickness-like disease
(26 days after fourth infusion of 375 mg/m2) occurring in a
patient treated with corticosteroids (10 mg/day) without any
other immunosuppressant agent. Three serious infections
occurred (1.3/100 patient-years): two bronchopulmonary infec-
tions (including one cytomegalovirus pneumopathy, 4 years
after the initiation or rituximab and 6 months after the fifth
cycle, associated with hypogammaglobulinaemia (4.3 g/l) at
the time of infection; one severe Staphylococcus aureus pneumo-
pathy treated in the intensive care unit, 4 years after the initi-
ation of rituximab and 9 months after the second cycle, with
normal levels of gammaglobulins at the time of infection; one
multiple dental infection (4 months after the second infusion
of the second cycle, with hypogammaglobulinaemia (5.6 g/l) at
the time of infection).
Two cancers (0.9/100 patient-years) occurred: one squamous
cell carcinoma of the vulva with hepatic and vertebral
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Table 3 Main series of patients with pSS treated with rituximab

No of serious
Control Glandular involvement/sytemic infections/serum
Source No Study design Drug (patients, no) (patients, no) involvement Primary outcome sickness-like diseases

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Gottenberg et al 8
6 Retrospective Rituximab 4×375 ms (n=5) None 1/5 Systemic involvement: 5/6 with systemic 0/1
study 2×375 ms (n=1) involvement
Seror et al9 16 Retrospective Rituximab 1 g/15 days (n=1) None 3/16 Systemic involvement: 4/5 patients with 0/1
study week 0 and 2 4×375 ms (n=14) lymphomas, 9/11 patients with systemic
6×375 ms (n=1) involvement.
Pijpe et al10 15 Open study Rituximab4×375 ms None 8/11 Significant improvement of subjective 1/3
symptoms and an increase in salivary gland
function was observed in patients with
residual salivary gland function
Devauchelle-Pensec 16 Open study Rituximab 1 g/15 days None 16/3 VAS scores with respect to fatigue and 0/1
et al11 dryness (p<0.05), tender point count
(p<0.035), and quality of life were
significantly improved
Ramos-Casals et al12 15 Registry Rituximab None 0/15 Systemic involvement: 10 (67%) complete 2/0
(BIOGEAS) response three (20%) partial response two
(13%) non responders
Tony et al13 6 Registry Rituximab mean (SD) dose None NR Two complete respnses two partial NR
(GRAID) (mg):2271 (995) responses
Mekinian et al14 Seventeen including Registry (AIR) Rituximab 4×375 ms (n=9) 1 g/ None 0/17 (PNS) Improvement in 11/17 PNS involvment 1/0
15 patients of the present 15 days (n=8)
study
Mekinian et al15 Eleven including Registry (AIR) Rituximab 1 g/15 days (n=9) None 0/11 (CNS) No neurological change occurred in nine 1/0
10 patients of the present 4×375 ms (n=2) patients. 2 patients were improved

Clinical and epidemiological research

study
Terrier et al16 Nine including 7 patients Registry (AIR) Rituximab 4×375 ms (n=8) 1 g/ None 0/9 (cryoglobulinemias) Nine clinical complete response six 0/2
of the present study and 15 days (n=1) immunologic complete response and three
1 of Mekinian’s study21 immunologic partial response
Dass et al6 17 RCT Rituximab 1 g/15 days (n=8) Placebo (n=9) 8/0 (rituximab group) Patients with>20% improvement in fatigue 1/1
(6 months) weeks 0 and 2 VAS (87% vs 56%, p=0.36)
Meijer et al5 30 RCT Rituximab 1 g/15 days (n=20) Placebo (n=10) Arthralgia: 15; synovitis: 6; renal Mean change from baseline of whole saliva 12/1
(48 weeks) weeks 0 and 2 involvement: 2; vasculitis: 6; flow rate (p=0.038 vs placebo)
polyneuropathy: 1 (rituximab group)
Present study 78 Registry (AIR) Rituximab 1 g/15 days (n=67) None 4/74 Systemic involvement: seven patients (60%) 3/1
4×375 ms (n=11) after the 1st cycle of rituximab, including 45
patients (61%) with systemic involvement
AIR, AutoImmune and Rituximab registry; CNS, central nervous system; cryo, cryoglobulinaemia; NR, not reported; PNS, peripheral nervous system; RCT, randomised controlled trial; SG, salivary gland; VAS, visual analogue scale.
1029
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Clinical and epidemiological research
metastases (11 months after rituximab initiation, two cycles),
one Paget’s cancer of the nipple with multiple metastases
(6 months after rituximab initiation, one cycle). Two deaths
occurred and were related to these cancers.
Levels of gammaglobulins were assessed at the initiation of
rituximab in 48 patients and 6 months after the first cycle in 22
patients. Hypogammaglobulinaemia (gammaglobulins < 6 g/l)
was observed after the first cycle of rituximab in four out of 22
patients (two with myositis and two with cryoglobulinaemia).
Before rituximab, one of these patients had hypogammaglobuli-
naemia, two had normal and one patient had increased levels of
gammaglobulins, which fell from 20.3 to 5.3 g/l. Two patients
with hypogammaglobulinaemia after rituximab developed a
serious infection and were subsequently retreated with rituxi-
mab and concomitant intravenous immunoglobulins.
Retreatments
Forty-one patients were retreated with rituximab (two cycles:
n=21; three cycles: n=8; four cycles: n=3; five to 12 cycles:
n=9). The median number of rituximab cycles was 2.3 (1–12).
The median duration between the first and second cycle was
11 months (5.4–29.4). The efficacy of rituximab according to
the clinician was observed in 16 of 21 patients treated with two
cycles, seven of eight patients treated with three cycles and 11
of 12 patients treated with four cycles or more. Eight patients
(two CNS involvements, one with transverse myelitis and one
with severe depressive and cognitive symptoms); two pulmon-
ary; one renal; one articular; one autoimmune anaemia; one
autoimmune pancreatitis) were persistent responders 30 months
(16–58) after their first cycle of rituximab and were not
retreated. After a median follow-up of 34.9 months (6–81.4),
rituximab was discontinued in 41 patients, including 26 patients
after the first cycle and 15 after more than one cycle (inefficacy:
35, serious adverse events: six patients, four after the first cycle,
one after the second cycle and one after the fifth cycle).
DISCUSSION
Our study shows that the use of rituximab in pSS in common
practice is mostly restricted to patients with systemic involve-
ment. In patients with pSS and systemic involvement, rituxi-
mab had a good efficacy (60%) and satisfactory tolerance. The
limitations of this study include its observational design, result-
ing in missing data and the definition of efficacy according to
the opinion of the physician. It is regrettable that no patient
data were collected on the evolution of dryness, fatigue and
pain. This might also be related to the fact that rituximab was
mainly prescribed for systemic complications.
The main messages of the present study therefore concern
the possible indications for rituximab in pSS and its safety in
this disease. Most of the patients treated with pSS previously
reported were treated with rituximab either for lymphoma,17 18
or for glandular involvement.19 The lack of data on the efficacy
of rituximab on systemic involvement other than lymphoma is
related to the limited proportion of patients with severe sys-
temic involvement compared to patients with dryness, pain
and fatigue. Moreover, patients with severe systemic involve-
ment were not included in the two controlled trials that com-
pared rituximab with placebo. In contrast, the objectives of
registries such as AIR are to collect data on efficacy and toler-
ance in real-life patients with refractory autoimmune diseases.
In France, inclusions in AIR have thus contributed to allow the
exceptional use of biological agents in SLE, pSS or vascu-
litis,16 20 21 thanks to ‘temporary therapeutic protocols’ pro-
vided by the French health agency. Therefore, the AIR registry
1030
allowed us to report the largest series of rituximab-treated
patients with systemic complications of pSS (table 3).
Regarding tolerance, charts were systematically reviewed for
serious adverse events, including infusion reactions, serious
infections and cancers. The rate of serious infections was lower
than observed in the same registry in RA or SLE.7 20 Four cases
of serious immediate reactions to infusions occurred, and there
was only one case of delayed serum sickness-like disease, an
adverse event that was previously reported in eight patients
with pSS (table 3).8 15 However, it is sometimes very difficult
to differentiate serious immediate reactions from serum sick-
ness disease. The main reason for discontinuing rituximab was
inefficacy and not adverse events. Interestingly, even in patients
with pSS and frequent hypergammaglobulinaemia, a decrease
in gammaglobulin levels after rituximab can be observed and
can be associated with the occurrence of serious infections. As
in RA, it is therefore recommended to monitor levels of gam-
maglobulins before each cycle of rituximab.22 23
Efficacy after the first cycle was observed in 60% of patients.
The majority of patients did not receive any other immunosup-
pressant agent than rituximab. The interpretation of the results
has to take into account the observational design and the defin-
ition of efficacy according to the opinion of the physician. Of
interest, in the majority of patients, it was possible to evaluate
modifications in objective parameters such as the number of
swollen joints, red or platelet blood count, proteinuria or glom-
erular filtration rate, for instance. Each clinician was asked to val-
idate the data collected in the registry and to provide his
assessment on the efficacy of rituximab. The importance of the
clinician’s assessment in heterogeneous and complex diseases was
recently emphasised by the inclusion of the physician’s global
assessment in the SLE responder index.24 The decrease in the
ESSDAI was another concordant appreciation of rituximab effi-
cacy. A decrease of at least 20% in the ESSDAI was observed in
two-thirds of the responders in whom the score had been
assessed. A decrease in corticosteroid dosage was also observed.
Forty-one patients (52.5%) received multiple cycles of rituximab,
including 20 patients who were prescribed three cycles or more.
Of course, the patients retreated with rituximab were those who
responded to the first cycle and tolerated it well. This can explain
their high rate of response to subsequent cycles. Interestingly, and
in contrast to RA, eight patients had persistent response after a
single cycle of rituximab. The main involvements that benefited
from rituximab were joints, vasculitis, autoimmune cytopaenias,
pulmonary and kidney involvement. The results were more disap-
pointing in PNS and CNS involvements without any vasculitis,
in which disease activity can be difficult to discriminate from
damage. No efficacy was observed in the three patients with mild
myositis, in contrast to positive results in other severe inflamma-
tory myopathies.21 Finally, the present study also showed the effi-
cacy of rituximab in severe parotid swelling, which is considered
by many clinicians to be a systemic complication.
In conclusion, the present study showed good efficacy and
tolerance of rituximab in patients with pSS and systemic
involvement. Controlled trials are now required to confirm the
therapeutic interest of rituximab in patients with pSS-related
systemic complications.
Author affiliations
1
Service de Rhumatologie, Centre National de Références des Maladies Auto-
Immunes Systémiques Rares, Hôpitaux Universitaires de Strasbourg,
Immunorhumathologie Moléculaire, INSERM UMR S 1109, Université de Strasbourg,
Strasbourg, France
2
Service de Médecine Interne et Maladies Infectieuses, HIA Legouest, Metz, France
3
Service de Médecine interne, CHU Avicenne, Bobigny, France
Ann Rheum Dis 2013;72:1026–1031. doi:10.1136/annrheumdis-2012-202293
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4
Service d'Immunorhumathologie, CHU Montpellier, Montpellier, France
5
Service de Médecine interne, CHU Lille, Lille, France
6
Service de Rhumatologie, Hôpital Bichat, Paris, France
7
Service de Rhumatologie, CH Pontoise, Pontoise, France
8
Service de Médecine interne, Hôpital de la conception, Marseille, France
9
Service de Rhumatologie, INSERM U957, CHU Nantes, Nantes, France
10
Service de Médecine Polyvalente - Rhumatologie, CH de La Rochelle, La Rochelle,
France
11
Service de Rhumatologie, CHU Tours, Tours, France
12
Service de Rhumatologie, CHU de Caen, Caen, France
13
Service de Pneumologie, Hôpital Saint Louis, Paris, France
14
Service de Médecine Interne, Hôpital Debré, Reims, France
15
Service de Rhumatologie, Groupe Hospitalier du Havre, Le Havre, France
16
Service de Médecine Interne, HIA Sainte-Anne, Toulon, France
17
Service de Rhumatologie, CHR Orléans, Orléans, France
18
Service de Rhumatologie, CHU Hôpital Sud, Grenoble, Echirolles, France
19
Service de Rhumatologie, CHU Lyon Sud France,
20
Service de Rhumatologie, CH Niort, Niort France
21
Service de Rhumatologie, CHU Ambroise Paré, Boulogne Billancourt, France
22
Service de Rhumatologie, CHU Rouen, Rouen, France
23
Service de Rhumatologie, Hôpital Lariboisière, Paris, France
24
Service de Médecine Interne, Hôpital Saint André, Bordeaux, France
25
Service de Médecine Interne, CHU de Nantes, Nantes, France
26
INSERM U738, Département d'Epidémiologie, Biostatistiques et Recherche Clinique,
Hôtel Dieu, Centre d'épidémiologie clinique, Paris, France
27
Service de Rhumatologie, Université Paris Sud, AP-HP, Hôpitaux Universitaires Paris
Sud, Paris, France
Acknowledgements The authors would like to thank the French Society of
Rheumatology (SFR), the Club Rhumatismes et Inflammation, the French National
Society of Internal Medicine (SNFMI) and Isabelle Pane (bioinformatician and data
manager of the AIR registry) for their involvement in the AIR registry, Rosemary
Jourdan (Roche), Jamila Filipecki and Nadine Mackenzie (formerly Roche). The
authors also thank the 14 research study nurses (A Bourgeois, E Braychenko, F
Carmet, MH Da Silva, S Delmas, D Guinement, R Lefebure, C Lehning, N Minot, FMA
Ouattara, V Pinosa, M Reau, H Thibault and E Wallet), L Dongmo, V Martin, all
working in Euraxipharma, the contract research organisation in charge of data
collection in the AIR registry.
Contributors JEG, GC and XM, designed the study, contributed to data collection,
analysed the data and drafted the manuscript. PR is the methodologist of the
registry. All the other authors contributed to data collection and analysed the data.
JEG and CG contributed equally.
Funding Roche provided an unrestricted educational grant but was not involved in
the design, protocol, data collection or statistical analysis of the study.
Competing interests None.
Ethics approval This study was approved by the Comité Consultatif sur le
Traitement de l’information en matière de Recherche dans le domaine de la Santé
and Commission Nationale de l’Informatique et des Libertés.
Patient consent Obtained.
Provenance and peer review Not commissioned; externally peer reviewed.
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 Downloaded from http://ard.bmj.com/ on December 22, 2014 - Published by group.bmj.com

Efficacy of rituximab in systemic

manifestations of primary Sjögren's
syndrome: results in 78 patients of the
AutoImmune and Rituximab registry
Jacques-Eric Gottenberg, Gael Cinquetti, Claire Larroche, Bernard
Combe, Eric Hachulla, Olivier Meyer, Edouard Pertuiset, Guy Kaplanski,
Laurent Chiche, Jean-Marie Berthelot, Bruno Gombert, Philippe Goupille,
Christian Marcelli, Séverine Feuillet, Jean Leone, Jean Sibilia, Charles
Zarnitsky, Philippe Carli, Stephanie Rist, Philippe Gaudin, Carine Salliot,
Muriel Piperno, Adeline Deplas, Maxime Breban, Thierry Lequerre,
Pascal Richette, Charles Ghiringhelli, Mohamed Hamidou, Philippe
Ravaud and Xavier Mariette

Ann Rheum Dis 2013 72: 1026-1031 originally published online

December 21, 2012
doi: 10.1136/annrheumdis-2012-202293

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http://ard.bmj.com/content/72/6/1026

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References This article cites 24 articles, 9 of which you can access for free at:
http://ard.bmj.com/content/72/6/1026#BIBL

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