Background/Purpose: Systemic sclerosis (SSc) is a severe, systemic
auto-immune disease with limited treatment options. Previous observational
studies showed possible efficacy of Rituximab (RTX), a monoclonal antibody
against CD20. Our objective was to evaluate safety and efficacy of RTX in
patients with SSc.

Methods: In this randomized, double-blind, placebo-controlled,
single centre trial, patients with SSc (ACR 1980
criteria), diagnosed less than 2 years ago,  were assigned to
receive either 1000mg RTX or placebo on day 1, 15 and at 6 months. Patients
were followed for 2 years with 3 monthly evaluation of modified Rodnan Skin
Score (mRSS) , pulmonary function, laboratory tests and 6 monthly evaluation of
high resolution CT thorax and cardiac ultrasound. Primary endpoints of the
study were treatment related mortality, treatment related toxicity and clinical
efficacy reflected by progression-free survival. Adverse
events (AE) and serious adverse events (SAE) were recorded every visit. Progression
was defined as  ³ 10% drop in Forced Vital Capacity (FVC )of predicted, and/or ³
15% drop in Diffuse Capacity of the Lung for Carbon Monoxide (DLCO) of
predicted, and/or  ³ 15% drop in left Ventricle Ejection fraction (LVEF), 
and/or ³ 15% drop in body weight, and/or ³ 30%
drop in creatinine clearance, and/or ³ 30% increase in mRSS on
2 consecutive visits.

Results:  Seventeen patients,  including 14 females
(82%), 11 Caucasians (65%), mean aged 39
(SD 14) years and a mean mRSS of 13 (SD 10), were included.  One patient did
not start treatment due to disease progression within
2 weeks after screening. Of the remaining patients, 8 received RTX  and
8 received placebo. At baseline, patients
characteristics were comparable between the groups.  Two patients dropped out
after 6 months, n = 1 (RTX)  at own request,
and  n = 1 (placebo) due to active disease.
This patient eventually died of a renal crisis after autologous stem cell transplantation.

After a median follow-up of 22 months (19-26 IQR), in total  90 AE (n=54
AE in n=8 for RTX; n=36 AE in n =8 for placebo; p=0,442) were reported of which
11 SAE (n=6 SAE in n= 5 for RTX; n=5 SAE in n=2 patients for placebo; p=0.335;
none could be related to RTX).  With placebo, disease progression according to
prespecified criteria was observed in 1 patient (T= 18 months; based on ³
30% increase in mRSS) , while progression free survival was 100% with
RTX (p=0.13).  Over time, no significant differences in mean mRSS, FVC, DLCO,
LVEF and creatinine clearance were observed between the groups (Table 1: mean
mRSS).

Conclusion: These preliminary results show that treatment with RTX
is well tolerated by SSc patients. Although no differences in clinical
parameters were observed between the groups, progression free survival was 100%
with RTX and 75% with placebo. More detailed analyses on clinical and
serological parameters, and functional ability scores, are currently being performed
to evaluate efficacy of RTX.