Drug Update

Anakinra - an overview
Sujatha MB1

www.kjoonline.org

Govt. Medical Introduction receptor antagonist that is currently FDA

College Thrissur
Anakinra is an Interleukin - 1 approved for moderate to severe
Kerala, India
receptor antagonist for the management Rheumatoid arthritis that has been
of joint disease in Rheumatoid arthritis unresponsive to initial disease modifying
1
Assoc. Professor (RA). anti rheumatic drug therapy.
of Pharmacology
Rheumatoid arthritis is a Structure
mulltifactorial disease in which there are The Anakinra molecule is a non
Correspondence
should be sent to: a number of genetic and environmental glycosylated version of human IL-1
mbsuja@gmail.com influences. There are significant receptor antagonist (IL-1RA) prepared
evidences that activation of T cells and from cultures of genetically modified
macrophages with the consequent E.Coli, using recombinant DNA
release of a number of inflammatory technology. It consists of 153 amino
cytokines play a role in the initiation and acids and has a molecular weight of 17.3
maintenance of both systemic and local Kilodaltons. It differs from native human
synovial inflammation in Rheumatoid IL-1 RA in that it has the addition of a
arthritis. In particular, tumor necrosis single methionine residue on its amino
factor, interleukin-1 and interleukin-6 are terminus (Figure 1).
considered the pivotal inflammatory Figure 1. Molecular structure of
mediators, contributing to its Anakinra
pathogenesis. IL-1 has been
demonstrated in a number of in vitro and
animal models to play a role in the
inflammation and joint destruction seen
in Rheumatoid arthritis. This includes
direct stimulation of cartilage degradation
process and inhibition of cartilage matrix
synthesis. IL-1 has also been
Available online at demonstrated to be a stimulatory
www.kjoonline.org
cytokine for both osteoclast precursor
differentiation and osteoclast activity,
Quick response code
likely indicating a further role in
osteopenia and joint destruction seen
with Rheumatoid arthritis.

In the last decade, a novel class of Mechanism of action

therapies directed against specific
cytokines implicated in the disease
Kerala Journal of
Orthopaedics process of Rheumatoid arthritis called
2012;25:51-54 the Biologics have greatly improved and
expanded the scope of treatment for
Kerala Journal of
Rheumatoid arthritis. Anakinra is an IL-1
Orthopaedics
Anakinra is the Biologic agent
designed specifically to modify the
biological immune response of IL-1.
Anakinra blocks the biologic activity of
naturally occurring IL-1 by competitively
inhibiting the binding of IL-1 to the IL-1

Kerala Journal Of Orthopaedics Volume 25 | Issue 1 | January 2011 51

 Drug Update
Sujatha MB.: Anakinra - an overview
Figure 2. Mechanism of action
receptor (Figure 2). Thus it is able to selectively
target the pathologic element of the disease. In
patients with RA, the natural IL-1 is not found in
effective concentration in synovium and synovial
fluid to counteract the elevated IL-1 concentration
in these patients.
Kinetics
Anakinra has an absolute bioavailability of
95% for healthy adults after subcutaneous
injection. Peak plasma concentration of Anakinra
generally occurred 3 to 7 hours after subcutaneous
administration of clinically relevant doses for
patients with Rheumatoid arthritis. The terminal t
1/2 ranged from 4 to 6 hours.
Clinical trials
To evaluate the efficacy and safety, Anakinra
have been assessed in five clinical trials involving
2846 patients.
Trials were conducted comparing Anakinra
alone or in combination with DMARDs or biologics
to placebo or other DMARDs or biologics in patients
above 18 years old with Rheumatoid arthritis. The
52 Kerala Journal of Orthopaedics Volume 25 | Issue 1 | January 2012
clinical response was measured according to
American College of Rheumatology (ACR ) criteria
(ACR 20, 50 &70).
After 24 weeks of treatment, the number of
participants achieving ACR 20 were significantly
higher with Anakinra 50 to 150 mg daily vs. placebo
(38% vs. 23%). Although this 15 % increase in
patients achieving ACR 20 with Anakinra versus
placebo was thought to be modest, it was also
thought to be clinically meaningful. Other efficacy
parameters - including ACR 50 (18% versus 7%),
ACR 70 (7% versus 2%), Health Assessment
Questionnaire, Visual analog scale for pain (VAS),
Larsen radiographic scores, and change in
Erythrocyte sedimentation rate (ESR) - all
demonstrated significant improvement with
Anakinra 50 to 150 mg daily versus placebo as well.
There were no statistically significant
differences noted in most safety outcomes with
treatment with Anakinra versus placebo, including
number of withdrawals, deaths, adverse events
(total and serious) and infections (total and
serious). An increase in incidence of serious

Sujatha MB.: Anakinra - an overview
infections in Anakinra versus placebo group (1.8%)
vs. (0.6%) was noted, that may be clinically
significant. Injection site reactions were
significantly increased, occurring in 71% Anakinra
vs. 25% of placebo group.
There are no direct studies comparing
Anakinra with TNF alpha inhibitors, but indirect data
suggests that Anakinra may be inferior to TNF alpha
inhibitors.
Therapeutic use & adverse effects
Anakinra was approved by the US Food and
Drug Administration and the European Commission
for the treatment of patients with Rheumatoid
arthritis in 2001. It is used to slow the progression
of moderate to severe active Rheumatoid arthritis
in patients over age 18 who has not responded to
one or more of the DMARDs. It can be combined
with other DMARDs. Since there is an increased risk
of serious infections in combination with Etanercept,
combination therapy with TNF alpha inhibitors is not
recommended.
Adverse effects primarily include injection site
reactions, recurrent infections, possibly pulmonary
infections with history of asthma / COPD and
possible risk of malignancy. In patients receiving
Anakinra, a decrease in neutrophil count may be
found. Neutrophil count should be assessed prior
to initiating Anakinra treatment and while receiving
Anakinra.
Preparation & Dosage
Anakinra - 100 mg, pre-filled syringes for
subcutaneous administration. The usual dosage is
100 mg subcutaneously once a day. Duration of
therapy is usually 24 weeks.
Conclusion
Anakinra, the first and only recombinant IL-1
receptor antagonist, is a relatively safe and
modestly efficacious biologic therapy for
Rheumatoid arthritis. More studies are needed to
evaluate safety and efficacy, especially in
comparison to other therapies. Adverse event data
for the long term use of Anakinra have yet to be
assessed.
Kerala Journal Of Orthopaedics Volume 25 | Issue 1 | January 2012
Drug Update
References
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for Clinical Excellence dated 30 March 2010
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Drug Update
Sujatha MB.: Anakinra - an overview

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Source of funding: Nil; Conflict of interest: Nil

Cite this article as:

Sujatha MB. Anakinra - an overview. Kerala Journal of Orthopaedics. 2012;25:51-54.

54 Kerala Journal of Orthopaedics Volume 25 | Issue 1 | January 2012