A Targeted Approach To Early Treatment With HUMIRA (Adalimumab) Shows Positive Results For Patients With Early RA

Main Category: Arthritis / Rheumatology
Article Date: 26 May 2011 – 4:00 PDT

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Abbott today announced the results of the second period
of OPTIMA, the first global study looking at different treatment strategies to achieve
positive outcomes in early rheumatoid arthritis (RA). It supports the Treat to Target
philosophy of achieving a clearly defined treatment goal within a set duration of time
and adjusting the treatment if the target is not met. The OPTIMA study was presented
at EULAR’s Annual European Congress of Rheumatology in London.

Results of the OPTIMA study demonstrated the value of targeted treatment
strategies, which resulted in improved disease control and reduced disease
progression in a significantly greater number of patients treated with a combination of
HUMIRA® (adalimumab) and methotrexate (MTX) vs. MTX alone1.

“The time that patients stay on treatments that aren’t working sufficiently is time lost,
because the damage to the joints is irreversible and can lead to irreversible loss of
physical function,” said Professor Josef Smolen, Chairman, Departments of
Rheumatology, Medical University of Vienna and Hietzing Hospital of Vienna, Austria.

“OPTIMA provided evidence that using Adalimumab early, or adding it in a timely
manner when methotrexate has not been effective based upon a predefined target,
can prevent further disease progression. This concept is consistent with EULAR
treatment recommendations.”

OPTIMA Study Findings

OPTIMA (Optimal Protocol for Treatment Initiation With Methotrexate and
Adalimumab Combination Therapy in Patients With Early Rheumatoid Arthritis) is a
multicenter, randomized, double-blind, 78-week two-period study that enrolled 1,032
MTX-naïve patients age 18 or older with early (less than one year) moderate to
severe RA. In period 1, patients were randomized to receive the combination of
HUMIRA 40 mg every other week (eow) and MTX or placebo and MTX for 26 weeks.
Patients in the combination therapy arm who achieved the target (defined as LDAS,

Findings include:

Period 1: Nearly twice as many patients treated with HUMIRA + MTX (207 of 466)
achieved the target response of sustained LDAS (DAS 28

Period 2: Significantly more patients who achieved the initial target response in
period 1 and who continued on HUMIRA + MTX (73 of 105, 70%) achieved the
composite outcome of a LDAS and no radiographic progression at week 78 compared
with those that achieved the initial target with placebo and MTX in period 1 and
continued to receive placebo + MTX (61 of 112, 55%) (p=0.02). For MTX patients that
did not achieve LDAS at weeks 22 and 26 who added HUMIRA (N=348), inhibition of
radiographic progression and improvement in clinical and functional outcomes at
week 52, after receiving 26 weeks of HUMIRA + MTX, was generally comparable to
MTX-naïve patients initially treated with HUMIRA + MTX for a period of 26 weeks
during period 1. Although the mean change in mTSS was 1.2, eighteen percent of
patients had demonstrated high levels of radiographic progression during period 1,
while receiving MTX monotherapy, prior to the initiation of HUMIRA + MTX.

Furthermore, the study also compared the effects of continuing combination treatment
vs. discontinuation of HUMIRA after achieving the target at weeks 22 and 26. Overall,
mean clinical, functional and radiographic outcomes (DAS28 scores, ACR responses,
mean HAQ-DI, mean mTSS and percent of patients with mTSS ≤ 0.5) were similar
for patients who achieved the sustained target and were re-randomized to either
HUMIRA + MTX or MTX alone. However, more patients remaining on HUMIRA +
MTX achieved DAS28

Adverse Events

Adverse events were reported by treatment arm for Period 1 and Period 2.
During period 1, the following events were experienced in 515 patients in the
HUMIRA plus MTX group compared with 517 patients in the placebo plus MTX group
respectively. Any serious adverse event, (7.2 percent vs 6.2 percent), Serious
Infection, (2.5 percent vs 1.2 percent), Opportunistic Infections excluding TB, (0.2
percent vs 0.6 percent), TB (0.2 percent vs 0 percent), malignancies excluding NMSC
(0.2 percent vs 0 percent), congestive heart failure (0.2 percent vs 0.2 percent) and
death (1.2 percent vs 0.2 percent).

During period 2, the following events were experienced in 102 patients in arm 1, 105
patients in arm 2, 259 patients in arm 3, 112 patients in arm 4 and 348 patients in arm
5 respectively: Any Serious adverse event (10.8 percent, 11.4 percent, 6.9 percent,
8.0 percent, 9.2 percent), serious infection (3.9 percent, 5.7 percent, 1.5 percent, 1.8
percent, 2.3 percent), opportunistic infections excluding TB (1.0 percent, 0 percent,
0.8 percent, 0.9 percent, 1.1 percent), TB (1.0 percent, 0 percent, 0 percent, 0
percent, 0.6 percent), malignancies excluding NMCS (1.0 percent, 0 percent, 1.2
percent, 1.8 percent, 0.6 percent), NMSC (0 percent, 0 percent, 0 percent, 0 percent,
0.9 percent), congestive heart failure (0 percent, 0 percent, 0.4 percent, 0 percent,
0.9 percent), and death (0 percent, 0 percent, 0.4 percent, 0 percent, 0.6 percent).
Adverse events among HUMIRA patients in this study were consistent with those
identified in the global HUMIRA clinical trial database1.

HUMIRA Indication

Globally, prescribing information varies; refer to the individual country label for
complete information.

Humira in combination with methotrexate, is indicated for:

– the treatment of moderate to severe, active rheumatoid arthritis in adult patients
when the response to disease-modifying anti-rheumatic drugs including
methotrexate has been inadequate

– the treatment of severe, active and progressive rheumatoid arthritis in adults not
previously treated with methotrexate.

Humira can be given as monotherapy in case of intolerance to methotrexate or when
continued treatment with methotrexate is inappropriate.
Humira has been shown to reduce the rate of progression of joint damage as
measured by X-ray and to improve physical function, when given in combination with

In addition, Humira is also approved for the treatment of polyarticular Juvenile
Idiopathic Arthritis (13-17 yrs), active and progressive Psoriatic Arthritis, severe,
active Ankylosing Spondylitis, severe, active Crohn’s Disease and moderate to severe
chronic plaque Psoriasis.

Important Safety Information

Before starting Humira, please note the following:

— Infection

– Do not use Humira in active, opportunistic or severe infections

– Caution if history of recurring infection, underlying predisposing conditions
(inc concomitant immunosuppressives) or travel to areas of high-risk of TB
or endemic mycoses e.g. histoplasmosis, coccidioidomycosis, or

– Particular caution regarding severe infections when treating elderly
patients over 65

— TB

– All patients should be screened for TB

– Do not use Humira in active TB

– If latent TB suspected, consult a TB specialist

– Consider anti-TB treatment in those with significant risk factors and a
negative test for latent TB, or a past history of treatment not confirmed as

— Malignancy

– Screen all patients for non-melanoma skin cancer, especially those with
history of extensive immunosuppressant or PUVA therapy

– Caution when considering Humira in patients with a history of malignancy

– Caution in patients with COPD or history of heavy smoking

— Heart failure

– Do not use in moderate to severe heart failure (NYHA class III/IV)

– Caution in mild heart failure (NYHA class I/II)

— Hepatitis B

– Patients at risk should be screened for prior evidence of HBV infection

— Demyelinating disorders

– Caution in patients with pre existing or recent-onset CNS demyelinating

— Allergic reactions

– Do not use in patients with known hypersensitivity to Humira or to any of
its components

— Pregnancy

– Humira is not recommended during pregnancy.

During Humira therapy, please note the following:

– Patients taking TNF-blockers are more susceptible to serious infections

– Monitor regularly for infection including TB and other opportunistic infections,
during and for 5 months after therapy. Instruct patients to seek medical advice if
signs/symptoms suggestive of TB or other infections occur. They need complete
diagnostic evaluation and appropriate antimicrobial or antifungal therapy should
be initiated

– Closely monitor HBV carriers for active HBV infection throughout therapy and for
several months after therapy

– Monitor for non-melanoma skin cancer

– Instruct patients to seek immediate medical attention if they develop
signs/symptoms of blood dyscrasias

– Discontinue Humira in cases of new, serious infection (until it is controlled), HBV
reactivation, new or worsening congestive heart failure, lupus-like syndrome with
ds-DNA antibodies and consider discontinuation if significant haematologic
abnormalities are confirmed

– Do not administer abatacept, anakinra or live vaccines

– Failure to respond to treatment for Crohn’s disease may indicate the presence of
fixed fibrotic stricture.
Undesirable effects

– Very commonly and commonly reported side effects include: respiratory tract
infections, leucopaenia, anaemia, raised lipids, headache, abdominal pain,
nausea and vomiting, rashes, musculoskeletal pain and injection site
reactions, infections, increased hepatic enzymes, benign neoplasms, nonmelanoma
skin cancer, thrombocytopenia, leucocytosis, hypersensitivity,
allergies, glucose and electrolyte imbalances, psychiatric disorders,
parasthesia, migraine, sciatica, visual impairment, conjunctivitis, vertigo,
tachycardia, hypertension, flushing, haematoma, cough, asthma, dyspnoea,
GI haemorrhage, dyspepsia, gastroesophageal reflux disease, sicca
syndrome, skin disorders, muscle spasms, haematuria, renal impairment,
chest pain, oedema, coagulation and bleeding disorders, impaired healing,
erythema multiforme, alopecia and diverticulitis

– Serious, including fatal, side effects have been reported including
infections/sepsis, intestinal perforation, opportunistic infections, TB, endemic
mycoses, demyelinating disease, malignancies including lymphoma (including
hepatosplenic T-cell lymphoma), leukaemia and skin cancer, cytopenias,
worsening heart failure, myocardial infarction, pulmonary embolism, pleural
effusion, pulmonary fibrosis, cerebrovascular accident, interstitial lung
disease, Stevens-Johnson syndrome, angioedema anaphylaxis and


1 Smolen JS et al. Poster THU0243 presented at EULAR, 2011



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