Two-year data from the
LITHE study, being presented at the American College of Rheumatology, show
that, with long-term use, patients with rheumatoid arthritis treated with
ACTEMRA (tocilizumab, known as RoACTEMRA within the EU) plus methotrexate (MTX)
suffered 81% less damage to their joints compared to those treated with MTX,
the current standard therapy, alone. For patients, this means that
their joint damage is significantly reduced, and that they can therefore
continue to enjoy their lives without the evolving disability usually associated
with the disease.
Furthermore, data from two long-term
extension studies also being presented at the meeting demonstrate
that the percentage of ACTEMRA patients achieving remission from their disease
(DAS28<2.6) increased steadily over a 3-year period, from 27% at 24 weeks to
62% at 180 weeks (3.4 years).
The unprecedented remission rates seen with
ACTEMRA were primarily the result of the profound effect on swollen and tender
joints across a range of patient populations:
·
Patients with no previous biologic therapy: After
96 weeks (1.8 years) of treatment with ACTEMRA, close to 50% of the patients
had one or less swollen joint
·
Patients with inadequate response to one or more
tumour necrosis factor (TNF) inhibitors: Among those patients 34% had one or
less swollen joint after treatment with ACTEMRA
·
Patients who were MTX-naive and were treated with
ACTEMRA as monotherapy: 55% had one or less swollen joint and 35% had one or
less tender joints after 96 weeks.
"These data confirm
that tocilizumab is very effective at inhibiting the damage to
joints which is characteristic of rheumatoid arthritis,” says Professor Josef
Smolen, University of Vienna, Austria. “This impressive effect on joints,
coupled with the previously shown ability of tocilizumab to provide relief from
the signs and symptoms of RA gives it an important role within clinical
practice. Successful remission with tocilizumab may help to restore a patient’s
sense of freedom, without painful flare-ups or fear of long-term
disability."
The long-term safety profile of ACTEMRA is
well characterised in 2.4 year data, being presented at the ACR,
from the most comprehensive registration trial programme for any RA biologic,
with almost 4,000 patients participating in the programme. Analysis from the
Phase III programme (including five pivotal trials and two long-term extension
studies) show that adverse events and
severe adverse events remained stable over extended periods of time.
About
the studies
About the
LITHE study
The LITHE study, a randomised, double-blind,
placebo-controlled trial was designed to evaluate the efficacy of TCZ plus MTX
in preventing structural joint damage and improving physical function over two
years. LITHE was an international study, including 15 countries and 1196 patients
with moderate to severe RA who had an inadequate response to MTX. In this
randomised study, patients received either ACTEMRA (4 mg/kg or 8 mg/kg, one
infusion every four weeks) in combination with MTX or MTX alone. Results from
the 24-month analysis showed that at 104 weeks, total Genant-modified Sharp
Score change from baseline for the ACTEMRA 8mg + MTX, 4mg +MTX, and MTX alone
groups were: 0.37, 0.58 and 1.96 respectively.
About the
long-term extension studies
Patients participating in the most comprehensive trial programme for
any biologic in RA including four pivotal studies (OPTION, TOWARD,
RADIATE, AMBITION), were entered into two long-term extension studies
(GROWTH95, GROWTH96), which examined safety and efficacy of ACTEMRA across a
number of different patient populations: DMARD insufficient response (IR),
anti-TNF-IR and monotherapy. Over 3,986 patients were included in the 2.4 year
safety, and 3.5 year efficacy analyses. Long-term extension studies have shown
low discontinuation rates due to side-effects (5.8/100 patient years).
About ACTEMRA
ACTEMRA is the result of research collaboration by Chugai and is being
co-developed globally with Chugai. ACTEMRA is the first humanised
interleukin-6 (IL-6) receptor-inhibiting monoclonal antibody. An extensive
clinical development programme of five Phase III trials was designed to
evaluate clinical findings of ACTEMRA, all of which met their primary
endpoints. ACTEMRA was first approved in Japan, and launched by Chugai in June
2005 as a therapy for Castleman's disease; in April 2008, additional
indications for RA, juvenile idiopathic arthritis and systemic-onset juvenile
idiopathic arthritis were also approved in Japan. ACTEMRA was approved in
the European Union in January 2009 for the treatment of RA in patients who have either
responded inadequately to, or who were intolerant to, previous therapy with one
or more disease modifying anti-rheumatic drugs (DMARDs) or TNF inhibitors. It is also
approved for use in several other countries, including India, Brazil,
Switzerland and Australia.
The overall safety profile of ACTEMRA is consistent across all global
clinical studies. The serious adverse reactions reported in ACTEMRA clinical
studies include serious infections, gastrointestinal perforations and hypersensitivity
reactions including anaphylaxis. The most common adverse reactions reported in
clinical studies were upper respiratory tract infection, nasopharyngitis,
headache, hypertension and increased ALT. Increases in liver enzymes (ALT and
AST) were seen in some patients; these increases were generally mild and
reversible, with no evidence of hepatic injuries or any observed impact on
liver function. Laboratory changes, including increases in lipids (total
cholesterol, LDL, HDL, triglycerides) and decreases in neutrophils and
platelets, were seen in some patients without association with clinical
outcomes. Treatments that suppress the immune system, such as ACTEMRA, may
cause an increase in the risk of malignancies.
