ASCO 2007 Breast Cancer Research

Report
New Evidence reports on presentations given at ACR 2009
Improving Radiographic, Clinical,
and Patient-Reported Outcomes with
Rituximab
From ACR 2009: Rituximab
 Rituximab in combination with methotrexate significantly
inhibits joint damage and improves clinical outcomes in
patients with early active RA who are refractory to
methotrexate (IMAGE)
(Tak P-P, et al. ACR 2009: Abstract 636)
 Rituximab improved physical function and quality of life in
patients with early rheumatoid arthritis who were naïve to
methotrexate (IMAGE-PRO)
(Rigby W, et al. ACR 2009: Abstract 1665)
 Identification of biomarkers for enhanced benefit to rituximab
in rheumatoid arthritis: role of autoantibodies and
inflammatory markers
(Silverman G, et al. ACR 2009: Abstract 1680)
From ACR 2009: Rituximab (cont’d)

Multiple courses of rituximab produce sustained efficacy
in rheumatoid arthritis patients with an inadequate
response to one or more TNF inhibitors
(Keystone E, et al. ACR 2009: Abstract 1683)

Long-term safety of rituximab: follow-up of the rheumatoid
arthritis clinical trials and re-treatment population
(Van Vollenhoven RF, et al. ACR 2009: Abstract 1952)

Safety of rituximab in combination with a TNF inhibitor
and methotrexate in patients with active rheumatoid
arthritis: results from a randomized, controlled trial
(TAME)
(Greenwald M, et al. ACR 2009: Abstract 1957)
Rituximab in combination with methotrexate
significantly inhibits joint damage and
improves clinical outcomes in patients with
early active RA who are refractory to
methotrexate (IMAGE)
Tak P-P, et al. ACR 2009: Abstract 636.
Background

In Canada, rituximab is currently indicated in combination with MTX for
the treatment of moderate-to-severe active rheumatoid arthritis in
patients with an inadequate response to tumour necrosis factor inhibitors
(TNF-Is).1

The IMAGE study is an ongoing phase III study designed to evaluate the
efficacy of rituximab plus MTX, compared to MTX alone, in patients with
active RA who are MTX-naïve.

At ACR 2009, Tak P-P and colleagues presented the primary efficacy
endpoint results of the IMAGE study.2
1. PRRITUXAN® Product Monograph. September 25, 2008.
2. Tak P-P, et al. ACR 2009: Abstract 636.
MTX = methotrexate
TNF-I = tumour necrosis factor inhibitor
Study design
Tak P-P, et al. ACR 2009: Abstract 636.
Study design (cont’d)

Key inclusion criteria for the IMAGE study were as follows:
• no prior exposure to MTX, with a disease duration of <4 years;
• SJC and TJC of ≥8 each;
• CRP concentration of ≥1.0 mg/dL;
• RF positive or erosive damage.

MTX was initiated in all groups at 7.5 mg/wk and titrated to 20 mg/wk
by week 8. Rituximab was given by intravenous infusion on days 1
and 15.

Radiographs were taken at screening, week 24, and week 52.

The primary endpoint was the change from screening in mTSS at
week 52.

Secondary endpoints included ACR and EULAR responses, MCR
defined as an ACR70 response maintained for at least 6 months, and
change in DAS28-ESR.
Tak P-P, et al. ACR 2009: Abstract 636.
CRP = C-reactive protein; DAS28 = 28-joint Disease Activity Score
ESR = erythrocyte sedimentation rate; MCR = major clinical response
mTSS = modified total sharp score; MTX = methotrexate
SJC = swollen joint count; TJC = tender joint count;
Key findings

A total of 755 patients were randomized, and 715 patients were
radiographically evaluable at 52 weeks.

Groups were well matched at baseline, with a mean RA duration of
0.9 years and DAS28 >7.

The mean change in DAS28-ESR score was –3.21, –3.05, and –2.06
in the rituximab (2 x 1000 mg) plus MTX, rituximab (2 x 500 mg) plus
MTX), and placebo plus MTX groups, respectively (p <0.0001 for all
comparisons with MTX).

SAEs occurred in 10%, 9%, and 10% of patients in the rituximab
(2 x 1000 mg) plus MTX, rituximab (2 x 500 mg) plus MTX, and
placebo plus MTX groups, respectively; the rate of SIEs per 100
patient-years was 3.73, 4.61, and 6.09, respectively.
Tak P-P, et al. ACR 2009: Abstract 636.
DAS28 = 28-joint Disease Activity Score
ESR = erythrocyte sedimentation rate; MTX = methotrexate
RA = rheumatoid arthritis; SAEs = serious adverse events
SIEs = serious infection events
Figure 1. Mean change in mTSS score after
52 weeks of treatment
Tak P-P, et al. ACR 2009: Abstract 636.
Figure 2. Percentage of patients with an
mTSS score ≤0 after 52 weeks of treatment
Tak P-P, et al. ACR 2009: Abstract 636.
Figure 3. Change in radiographic scores by six month periods
Tak P-P, et al. ACR 2009: Abstract 636.
Figure 4. ACR responses and MCR after 52 weeks of treatment
Tak P-P, et al. ACR 2009: Abstract 636.
Figure 5. EULAR responses after
52 weeks of treatment
Tak P-P, et al. ACR 2009: Abstract 636.
Key conclusions

After 52 weeks of treatment in patients with early active
rheumatoid arthritis, rituximab (2 x 1000 mg) significantly
inhibited joint damage, as compared to methotrexate alone.

Both higher (2 x 1000 mg) and lower (2 x 500 mg) doses of
rituximab plus methotrexate significantly improved clinical
outcomes, as compared with methotrexate alone.

A significantly higher proportion of patients achieved a major
clinical response with both doses of rituximab, as compared to
methotrexate alone.

Safety outcomes were consistent with previous data, and no new
or unexpected safety signals were identified.
Tak P-P, et al. ACR 2009: Abstract 636.
Rituximab improved physical function
and quality of life in patients with
early rheumatoid arthritis who were
naïve to methotrexate (IMAGE-PRO)
Rigby W, et al. ACR 2009: Abstract 1665.
Background

Patients with rheumatoid arthritis (RA) live with considerable
physical, social, and emotional disabilities.

Improving HRQoL is therefore an important treatment goal, with
the value of collecting PROs in clinical trials becoming increasingly
apparent.

IMAGE-PRO is an ongoing study using PRO data from the IMAGE
study to examine the effect of rituximab in combination with MTX,
as compared with MTX alone, in patients with active RA who are
MTX-naïve.

At ACR 2009, Rigby and colleagues presented data from the
IMAGE-PRO study.
Rigby W, et al. ACR 2009: Abstract 1665.
HRQoL = health-related quality of life
MTX = methotrexate
PRO = patient-reported outcome
Study design

Patients included in the IMAGE study:
• had no prior exposure to MTX, with a disease duration
of <4 years
• had a swollen and tender joint count of ≥8 each
• had a C-reactive protein concentration of ≥1.0 mg/dL
• were rheumatoid factor positive or exhibited erosive damage

Patients were randomized to receive placebo plus MTX, rituximab
(2 x 500 mg) plus MTX, or rituximab (2 x 1000 mg) plus MTX.

MTX was initiated in all groups at 7.5 mg/wk and titrated to 20 mg/wk by
week 8. Rituximab was given by intravenous infusion on days 1 and 15.

PRO instruments included the SF-36 PCS and MCS scores;
the HAQ-DI; the FACIT-Fatigue scale; and the PGA and Pain, measured
using the VAS.
Rigby W, et al. ACR 2009: Abstract 1665.
FACIT = Functional Assessment of Chronic Illness Therapy
HAQ-DI = Health Assessment Questionnaire – Disability Index;
MCS = Mental Component Summary score; MTX = methotrexate
PCS = Physical Component Summary score
PGA = Patient Global Assessment of Disease Activity
SF-36 = 36-item Short Form Health Survey
VAS = Visual Analogue Scale
Key findings

A total of 755 patients were randomized, and 748 were included in the ITT
population and received at least one treatment dose.

Of these, 620 (83%) patients had early RA (<2 years).

Patient demographics, baseline disease characteristics, and PRO scores
were well balanced across groups.

In post hoc analyses, greater numeric improvements from baseline to
week 52 were observed for both rituximab plus MTX dose groups, versus
MTX alone, in all eight domains of the SF-36.

An MCID of >0.22 for HAQ was achieved by a greater proportion of patients in
both rituximab plus MTX dose groups, compared with patients who received
MTX alone (p <0.05).

MCID was achieved in a greater proportion of patients in the rituximab
(2 x 1000 mg) plus MTX group, compared with the placebo plus MTX group,
for SF-36 (both PCS and MCS) and FACIT-Fatigue (p <0.05).
Rigby W, et al. ACR 2009: Abstract 1665.
FACIT = Functional Assessment of Chronic Illness Therapy
HAQ-DI = Health Assessment Questionnaire –Disability Index
MCID = minimal clinically important difference
MCS = Mental Component Summary score
MTX = methotrexate; SF-36 = 36-item Short Form Health Survey
PCS = Physical Component Summary score; PRO = patient reported outcomes;
Figure 1. Mean change from baseline to week 52
in HAQ-DI
Rigby W, et al. ACR 2009: Abstract 1665.
Figure 2. Mean change from baseline to week 52
in FACIT-Fatigue
Rigby W, et al. ACR 2009: Abstract 1665.
Figure 3. Mean change from baseline to week 52
in Patient Global Score
Rigby W, et al. ACR 2009: Abstract 1665.
Figure 4. Mean change from baseline to week 52
in Pain Score
Rigby W, et al. ACR 2009: Abstract 1665.
Figure 5. Mean change from baseline to week 52 in SF-36 summary
and domain scores
Rigby W, et al. ACR 2009: Abstract 1665.
Key conclusion

Rituximab in combination with methotrexate showed significant
improvement in physical function and health-related quality of life
outcomes, as compared with methotrexate alone.
Rigby W, et al. ACR 2009: Abstract 1665.
Identification of biomarkers for enhanced benefit
to rituximab in rheumatoid arthritis: role of
autoantibodies and inflammatory markers
Silverman G, et al. ACR 2009: Abstract 1680.
Background

Identifying markers associated with improved outcomes after
rituximab therapy enables the selection of patient groups with
an enhanced response to rituximab.

Knowledge of these markers can aid in the management of
patients with rheumatoid arthritis (RA).

A study by Silverman and colleagues used data from the
REFLEX and SERENE trials to examine markers, clinical
features, and/or combinations of these associated with
improved outcomes after rituximab therapy.

At ACR 2009, Silverman and colleagues presented data from
their study.
Silverman G, et al. ACR 2009: Abstract 1680.
Study design

The REFLEX study was a double-blind, placebo-controlled,
phase III RCT conducted in RA patients with a previous inadequate
response to TNF-Is.

SERENE was a second double-blind, placebo-controlled, phase III
RCT conducted in RA patients with an inadequate response
to MTX.

The study by Silverman and colleagues was a post hoc analysis of
selected biomarkers, clinical features, and serologic markers using
data from the REFLEX study, and further examining promising
markers that showed potential response prediction in the SERENE
data set.

Baseline pre-treatment samples and clinical data from the REFLEX
and SERENE studies were used to conduct this analysis.
Silverman G, et al. ACR 2009: Abstract 1680.
REFLEX = randomized evaluation of long-term efficacy of rituximab in RA
SERENE = study evaluating rituximab’s efficacy in methotrexate inadequate responders
MTX = methotrexate; RCT = randomized controlled trial
TNF-Is = tumour necrosis factor inhibitors
Study design (cont’d)
Silverman G, et al. ACR 2009: Abstract 1680.
Study design (cont’d)

A threshold sensitivity method was used to identify candidate
markers/clinical features that enriched for placebo-corrected ACR50
response rate at 24 weeks and were able to identify at least 20% of
patients from the REFLEX study.

The top four markers and five of their two-marker combinations were
then prioritized and further investigated in the SERENE data set.

For the combination of two markers, the hypothesis that CRP-high and
RF IgA–high patients have improved clinical efficacy was tested.

Subgroups were determined by 30th–70th percentile categories of CRP
and RF IgA, with the constraint that at least 20% of the patients were in
each subgroup. Other combinations were investigated similarly.

Exploratory analysis of other pre-specified baseline biomarkers and
combinations of markers were also performed.
Silverman G, et al. ACR 2009: Abstract 1680.
CRP = C-reactive protein; IgA = immunoglobulin A
RF = rheumatoid factor
Key findings

Improved clinical benefit was observed in the REFLEX data set for
the following serological markers: RF IgA, IgG anti-CCP antibodies,
CRP, and soluble CD25.

These four biomarkers, as well as clinical features of disease activity
(DAS-ESR), and five of their two-marker combinations were then
further investigated in the SERENE data set.

CRP was selected over IL-6 to be further examined because of its
clinical relevance and readily available standardized tests.

The efficacy differentials were higher than 10% for RF IgA and CRP
in SERENE, based on the optimal thresholds obtained from REFLEX.
Silverman G, et al. ACR 2009: Abstract 1680.
anti-CCP = anti-cyclic citrullinated peptide antibody; CRP = C-reactive protein
DAS-ESR = disease activity score-erythrocyte sedimentation rate
IgA = immunoglobulin A; IL-6 = interleukin-6; RF = rheumatoid factor;
Key findings (cont’d)

In discovery studies, it was determined that, compared to
seronegative patients, seropositivity for any isotypes of RF or IgG
anti-CCP antibodies was associated with a higher rate of placebocontrolled ACR50 response at 24 weeks.

Enhanced benefit to rituximab was independently confirmed in the
SERENE study, as observed by the association of elevated CRP and
seropositive RF IgA.

The greatest enhancement was seen with the CRP plus IgA RF
combination.
Silverman G, et al. ACR 2009: Abstract 1680.
anti-CCP = anti-cyclic citrullinated peptide antibody
CRP = C-reactive protein; IgA = immunoglobulin A
IgG = immunoglobulin G; RF = rheumatoid factor;
Key findings (cont’d)

The optimal individual thresholds determined in SERENE for CRP
(2.9 mg/dL) and IgA RF (25 U/mL) were used for the combination of
these two biomarkers.

These patients also had improved clinical responses across a
spectrum of other clinical outcome measures.

Elevated CRP in combination with seropositive RF isotypes showed
enhanced clinical benefit to rituximab.

The CRP/RF isotype combinations shown in the SERENE trial data
set were confirmed in the REFLEX data set.
Silverman G, et al. ACR 2009: Abstract 1680.
CRP = C-reactive protein; IgA = immunoglobulin A
RF = rheumatoid factor
Figure 1. ACR50 response rate differences at week 24 for the marker combination
of elevated C-reactive protein and IgA rheumatoid factor in the SERENE data set
Silverman G, et al. ACR 2009: Abstract 1680.
Table 1. Summary of marker combination versus clinical parameters in the SERENE data set
Silverman G, et al. ACR 2009: Abstract 1680.
Key conclusions

In the REFLEX study, seropositivity for rheumatoid factor or antiCCP antibody and elevated CRP identified a subgroup of RA
patients with an enhanced efficacy to rituximab; these findings were
reproduced in the SERENE trial.

The identified biomarkers and thresholds which confer enhanced
benefit need to be verified in independent data sets.

High CRP and seropositivity indicate that patients who have high
levels of systemic inflammation and autoantibody driven disease
seem to benefit from rituximab therapy.

Further studies are needed to understand the pathophysiology of
this subset of RA patients.
Silverman G, et al. ACR 2009: Abstract 1680.
anti-CCP = anti-cyclic citrullinated peptide antibody; CRP = C-reactive protein
Multiple courses of rituximab produce
sustained efficacy in rheumatoid arthritis
patients with an inadequate response to
one or more TNF inhibitors
Keystone E, et al. ACR 2009: Abstract 1683.
Background

Despite the success of rituximab for the treatment of RA in patients
who have had an inadequate response (IR) to TNF-Is, whether
repeat courses result in sustained efficacy remains unclear.

A meta-analysis of open-label extension studies examined the
efficacy of repeat courses of rituximab in TNF-IR patients who had
previously responded to a first or second course.

At ACR 2009, Keystone and colleagues presented results of the
meta-analysis.
Keystone E, et al. ACR 2009: Abstract 1683.
RA = rheumatoid arthritis;
TNF-I = tumour necrosis factor inhibitor
Study design

Studies included in the meta-analysis study1 were
REFLEX/WA175312, DANCER3, WA162914, WA168555, MIRROR6,
SIERRA7, and SUNRISE8.

In the majority of studies, eligibility for re-treatment included a
response to the first/second course (at least a 20% reduction in
swollen and tender joint counts).

Each course consisted of rituximab (2 x 1000 mg) given as
intravenous infusions two weeks apart and concomitant MTX
(10–25 mg/week).

Before all infusions, patients received prophylactic intravenous
methylprednisone (100 mg). Background stable-dose oral
corticosteroids (≤10 mg/day prednisolone or equivalent) and nonsteroidal anti-inflammatory drugs (NSAIDs) were also permitted.
1. Keystone E, et al. ACR 2009: Abstract 1683.
2. Cohen SB, et al. Arthritis Rheum 2006;54:2793–2806.
3. Emery P, et al. Arthritis Rheum 2006;54:1390–1400.
4. Edwards JC, et al. N Engl J Med 2004;350:2572–2581.
5. Keystone E, et al. Arthritis Rheum 2007;65:3896–3908.
6. Rubbert-Roth A, et al. Arthritis Rheum 2008; Abstract 363.
7. Bingham C, et al. Arthritis Rheum 2007; Abstract 1999.
8. Mease PJ, et al. Arthritis Rheum 2008; Abstract 1212.
MTX = methotrexate
Study design (cont’d)

Efficacy analyses were confined to TNF-IR patients who received
continuous treatment with the approved dose of rituximab
(2 x 1000 mg).1

Patients who initially received placebo and were subsequently treated
with rituximab (2 x 1000 mg) were included from the point at which
they first received rituximab.

Patients from the SIERRA2 and SUNRISE3 studies were not included
in the efficacy population due to incompatible study designs.

Efficacy data included:
• all observed data: all patients, all visits, all courses – all data
available at a given time point;
• within patient, within visit: data for patients who have received
four courses of treatment and had efficacy data at week 24 after
each course.
1. Keystone E, et al. ACR 2009: Abstract 1683.
2. Bingham C, et al. Arthritis Rheum 2007; Abstract 1999.
3. Mease PJ, et al. Arthritis Rheum 2008; Abstract 1212.
MTX = methotrexate; NSAID = non-steroidal anti-inflammatory drugs
TNF-IR = tumour necrosis factor inhibitor inadequate responder
Key findings

In total 1,324 TNF-IR patients were exposed to at least one course
of rituximab.

The highest incidence of withdrawals due to adverse events occurred
during the first treatment course and decreased with subsequent
courses.

A total of 595 TNF-IR patients were exposed to at least
one course of rituximab (2 x 1000 mg). Of these, 500 patients
had evaluable efficacy assessments at week 24 following their
first course.

Safety over repeated courses did not show any unexpected findings.

Over 3,122.80 p-yrs of observation in TNF-IR patients, the overall rate
of serious adverse events was 20.17/100 p-yrs, and the overall rate of
serious infection events was 5.44/100 p-yrs.
Keystone E, et al. ACR 2009: Abstract 1683.
p-yrs = patient-years
TNF-IR = tumour necrosis factor inhibitor inadequate responder
Keystone E, et al. ACR 2009: Abstract 1683.
Figure 1. ACR responses 24 weeks after each course in the within
patient, within visit population
Keystone E, et al. ACR 2009: Abstract 1683.
Figure 2. EULAR responses 24 weeks after each course
in the within patient, within visit population
Keystone E, et al. ACR 2009: Abstract 1683.
Figure 3. DAS28-ESR low disease activity and remission 24 weeks
after each course in the within patient, within visit population
Keystone E, et al. ACR 2009: Abstract 1683.
Key conclusions

In RA patients with a previous inadequate response to TNF
inhibitor(s) and an initial response to rituximab, multiple courses of
rituximab were associated with sustained levels of efficacy.

Signs, symptoms, and physical function were maintained, with
a trend towards improvement.
Keystone E, et al. ACR 2009: Abstract 1683.
Long-term safety of rituximab: follow-up
of the rheumatoid arthritis clinical trials
and re-treatment population
Van Vollenhoven RF, et al. ACR 2009: Abstract 1952.
Background

Despite the success of rituximab for the treatment of rheumatoid
arthritis (RA) patients who have had an inadequate response (IR) to
tumour necrosis factor inhibitors (TNF-Is), the safety of repeat
courses is unclear.

An ongoing study of pooled data from a global clinical trial program is
examining the long-term safety of rituximab in combination with
methotrexate (MTX) in patients with RA.

At ACR 2009, Van Vollenhoven and colleagues presented interim
results of this long-term safety study.
Van Vollenhoven RF, et al. ACR 2009: Abstract 1952.
Study design

The study by Van Vollenhoven and colleagues is a pooled analysis
of data from a global clinical trial program.

All patients in the program were offered repeat treatment with
rituximab, as determined by clinical need.

Patients receiving placebo during placebo-controlled studies were
pooled to provide a placebo population.

Data were collected on adverse events (AEs), including infusion
reactions, infections, and malignancies.

Serious infusion reaction events were defined as evidence of
pruritus, fever, urticaria/rash, chills, pyrexia, rigors, sneezing,
angioneurotic oedema, throat irritation, cough, bronchospasm,
hypotension, or hypertension.
Van Vollenhoven RF, et al. ACR 2009: Abstract 1952.
Key findings

As of September 2008, this analysis was based on 7,198 p-yrs
of rituximab exposure.

A total of 3,095 patients with RA received multiple courses of
rituximab: 2,365; 1,581; 1,038; and 497 patients received ≥2, ≥3, ≥4,
and ≥5 courses, respectively.

More than 750 patients were followed for >3 years from start of
treatment.

IRRs from rituximab were mainly grade 1 or 2 and occurred after the
first infusion of the first course (23%). Fewer than 1% of IRRs were
considered serious.

The most frequent serious infections were of the lower respiratory tract,
predominantly pneumonia (1%).

No cases of TB or reactivation of hepatitis B were reported.
Van Vollenhoven RF, et al. ACR 2009: Abstract 1952.
IRR = infusion-related reaction; p-yrs = patient years
SIE = serious infection event; TB = tuberculosis
Key findings (cont’d)

Serious opportunistic infections were uncommon, but included one
confirmed case of Pneumocystis jiroveci pneumonia in each of the
rituximab and pooled placebo groups, and one case of PML in the
rituximab group.

The causal relationship of PML to rituximab in this case was unclear
due to recognized risk factors, including carcinoma of the
oropharynx treated by chemoradiotherapy.

Rates of MI and stroke were consistent with the general RA
population. The SIR for malignancy compared with the SEER 2008
database was 1.06 (95% CI: 0.81–1.37).

The most frequently reported malignancy (excluding non-melanoma
skin cancer) was breast cancer (SIR 0.69; 95% CI: 0.35–1.24).
Van Vollenhoven RF, et al. ACR 2009: Abstract 1952.
MI = myocardial infarction
PML = progressive multifocal leukoencephalopathy
SIR = standardized incidence ratio
Van Vollenhoven RF, et al. ACR 2009: Abstract 1952.
Van Vollenhoven RF, et al. ACR 2009: Abstract 1952.
Key conclusion
 In a prolonged follow-up of RA patients treated with rituximab in
clinical trials, rituximab has remained well tolerated over
multiple courses with a stable safety profile similar to the
placebo population.
Van Vollenhoven RF, et al. ACR 2009: Abstract 1952.
Safety of rituximab in combination with
a TNF inhibitor and methotrexate in patients
with active rheumatoid arthritis: results from
a randomized, controlled trial (TAME)
Greenwald M, et al. ACR 2009: Abstract 1957.
Background

Despite the success of rituximab for the treatment of rheumatoid
arthritis (RA) patients who have had an inadequate response (IR)
to TNF-Is, the safety of combination treatment with rituximab and
TNF-Is is unclear.

An ongoing open-label study (TAME) is examining the safety of
rituximab in combination with a TNF-I, etanercept or adalimumab,
plus methotrexate (MTX) in patients with active RA.

At ACR 2009, Greenwald and colleagues presented preliminary data
of the TAME study.
Greenwald M, et al. ACR 2009: Abstract 1957.
Study design

Patients included in the TAME study:
• had active RA (swollen joint count ≥5 and tender joint count ≥5);
• had been receiving etanercept (50 mg once per week) or
adalimumab (40 mg every two weeks) plus MTX (10–25 mg
once per week) for 12 weeks or more.

Patients were randomized 2:1 to rituximab (500 mg) or placebo on
days 1 and 15.

After week 24, eligible patients could enter the open-label rituximab
treatment arm.

The primary endpoint was the proportion of patients who
experienced ≥1 serious infection through week 24.

Secondary endpoints included additional safety and efficacy
parameters.
Greenwald M, et al. ACR 2009: Abstract 1957.
MTX = methotrexate
Key findings

Fifty-one (51) patients received at least one dose of study treatment,
33 in the rituximab group and 18 in the placebo group.

Baseline characteristics and concomitant TNF-Is were balanced
between treatment groups, with the exception of oral steroid use
(36% for the rituximab group versus 17% for the placebo group).

There were 2 patients (6%) with SAEs in the rituximab group and
0 in the placebo group.

Through week 24, there was 1 serious infection in 15.55 p-yrs of
exposure in the rituximab group (6.43 events per 100 p-yrs;
95% CI: 0.91–45.65) and 0 in the placebo group.

No further serious infections in 46.35 p-yrs (2.16 events per 100 p-yrs;
95% CI: 0.30–15.32) in patients receiving 1 or 2 courses of rituximab
were observed.
Greenwald M, et al. ACR 2009: Abstract 1957.
p-yrs = patient-years; SAE = serious adverse event
Greenwald M, et al. ACR 2009: Abstract 1957.
Figure 1. ACR20 and ACR50 response rates after
24 weeks of treatment with rituximab versus placebo
Greenwald M, et al. ACR 2009: Abstract 1957.
Key conclusions

The preliminary safety profile for rituximab in combination with a
TNF-I (etanercept or adalimumab) and MTX was consistent with the
safety profile for rituximab with MTX in other RA trials without a
TNF-I; no new safety signals were seen.

A larger open-label study evaluating the safety profile for rituximab
in combination with TNF-Is and DMARDs is in progress.
Greenwald M, et al. ACR 2009: Abstract 1957.
DMARD = disease-modifying anti-rheumatic drug
MTX = methotrexate
TNF-I = tumour necrosis factor inhibitor

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