Adalimumab
Adalimumab is a recombinant human monoclonal 1NF antibody that binds specifically to 1NF-a and blocks its interaction with endogenous cell-surface 1NF receptors.
Uses and Administration
Adalimumab is a recombinant human
monoclonal 1NF antibody that binds
specifically to 1NF-a and blocks its
interaction with endogenous
cell-surface 1NF receptors. It also
modulates biological responses that
are induced or regulated by 1NF.
Elevated levels of 1NF have been
found in the affected tissues and
fluids of patients with rheumatoid
arthritis, axial spondyloarthritis,
ankylosing spondylitis, and
psoriatic arthritis, plaque
psoriasis (below), and Crohn's
disease and ulcerative colitis.
Adalimumab is described as a
biological disease modifying
antirheumatic drug (DMARD).
Adalimumab is used in the treatment
of moderate to severe, active
rheumatoid arthritis and active and
progressive psoriatic arthritis. In
the UK, it is licensed for use in
patients who have had an inadequate
response to standard DMARDs,
although in severe progressive
rheumatoid arthritis it may be used
in patients not previously treated
with methotrexate; in the USA, it is
licensed for use in early disease.
Adalimumab is also used in the
treatment of active ankylosing
spondylitis: UK licensed product
information recommends that it
should only be used in patients with
severe disease who have had an
inadequate response to conventional
treatment; however, in the USA it
may be used in early disease. In the
UK, it is also used in the treatment
of severe axial spondyloarthritis
without radiographic evidence of
ankylosing spondylitis in patients
who have had an inadequate response
to, or are intolerant of, NSAIDs.
For all the above indications, it is
given by subcutaneous injection in a
dose of 40 mg every other week. In
the treatment of rheumatoid
arthritis, UK licensed product
information recommends that
adalimumab should be given with
methotrexate, although monotherapy
may be used where treatment with
methotrexate would be inappropriate.
When used as monotherapy in
rheumatoid arthritis, some patients
may benefit from increasing the dose
to 40 mg every week. In the UK, NICE
recommends that adalimumab be
stopped if there is no adequate
response after 6 months for the
treatment of rheumatoid arthritis,
and after 12 weeks for psoriatic
arthritis or ankylosing spondylitis.
Adalimumab is used in the treatment
of moderate to severe, active
Crohn's disease and ulcerative
colitis unresponsive to conventional
treatment; it may also be used in
patients with Crohn's disease who
have relapsed while taking
infliximab. For both these
indications, patients may be given
an initial dose of 160 mg
subcutaneously on day 1 (given as
four 40-mg injections in one day or
two 40-mg injections daily for 2
consecutive days), followed by 80 mg
two weeks later (day 15 ) . After a
further two weeks (day 29), a
maintenance dose of 40 mg every
other week may be started. There is
a high risk of adverse effects
associated with the above induction
dose, consequently, in those with
Crohn's disease who do not require a
more rapid response to therapy, UK
licensed product information advises
that a lower dose of 80 mg may be
given initially, followed by 40 mg 2
weeks later; thereafter, usual
maintenance doses may be given. A
clinical response is usually seen
within 8 or 12 weeks of starting
treatment for ulcerative colitis or
Crohn's disease, respectively; for
both indications, those patients who
relapse while on adalimumab may
benefit from increasing the
maintenance dose to 40 mg every
week.
In the treatment of
moderate to severe chronic plaque
psoriasis in patients unresponsive
to, or intolerant of, conventional
systemic therapy including
phototherapy, the recommended
initial dose of adalimumab is 80 mg
subcutaneously; this may be followed
by a maintenance dose of 40 mg
subcutaneously on alternate weeks,
starting 1 week after the initial
dose. A clinical response is usually
seen within 16 weeks of starting
treatment.
For the uses of adalimumab in
children, and recommended doses, see
below.
Administration in children
Adalimumab is used in the treatment
of active polyarticular juvenile
idiopathic arthritis in children. In
the UK, it is licensed for use in
those aged 2 years and older who
have had an inadequate response to
standard disease-modifying
antirheumatic drugs (DMARDs). The
dose in children aged 2 to 12 years
is calculated according to
body-surface and is given
subcutaneously: 24 mg/m2 up to a
maximum dose of 20 mg in those
younger than 4 years of age and 40
mg in those aged 4 to 12 years may
be given every other week. Older
children may receive 40 mg every
other week regardless of
body-surface area. licensed product
information also recommends that it
should be given with methotrexate,
although monotherapy may be used
where treatment with methotrexate is
inappropriate. In the USA,
adalimumab is licensed for use in
children aged 4 to 17 years to
reduce the signs and symptoms of
moderately to severely active
disease; the dose is calculated
according to body weight and is
given subcutaneously: those weighing
15 kg to less than 30 kg should be
given 20 mg every other week, while
heavier children may receive 40 mg
every other week.
In the UK, adalimumab is also licensed for the treatment of severe, active Crohn's disease in children aged 6 years and older who have had an inadequate response to conventional therapy, or who have contra-indications for or are intolerant of such treatments. The dose is given subcutaneously, according to body-weight: those weighing less than 40 kg should be given an initial dose of 80 mg on day 1, followed by 40 mg 2 weeks later (day 1 5). After a further 2 weeks (day 29), a maintenance dose of 20 mg every other week may be started. There is a high risk of adverse effects associated with the above induction dose, consequently, in those who do not require a more rapid response to therapy, licensed product information advises that a lower dose of 40 mg may be given initially, followed by 20 mg 2 weeks later; thereafter, usual maintenance doses may be given. Patients who have an insufficient response may benefit from increasing the maintenance dose to 20 mg every week. Heavier children may be given the usual adult dose for this indication.
Hidradenitis suppurativa
For
mention of adalimumab having been
used in the treatment of
hidradenitis suppurativa
Adalimumab is used in the management
of inflammatory bowel disease such
as Crohn's disease and ulcerative
colitis. It has also been tried in
children 10-12 years old.
1.
Plosker GL, Lyseng-Williamson KA.
Adalimumab: in Crohn's disease.
BioDruos 2007; II: 125-32.
2.
NICE. Infliximab and adalimumab for
the treatment of Crohn's disease
(includes a review of NICE
technology appraisal guidance 40):
Technology Appraisal Guidance 187
(issued May 2010). Available at:
http: /
/www.nice.org.uk/nicemedia/live I 1
2 9 8 5/48 5 52/485 5 2 . pdf
(accessed 19/10/IO)
3. Huang ML,
et al. Efficacy and safety of
adalimumab in Crohn's disease:
meta-analysis of placebo-controlled
trials. J Dis Dis 2011; 12: 165-72.
4. Guidi L, et al. Update on the
management of inflammatory bowel
disease: specific role of
adalimumab. Clin Exp Gastroenterol
2011; 4: 1 6 3-72.
5. Wasan SK,
Kane SV. Adalimumab for the
treatment of inflammatory bowel
disease. Expert Rev Gastroenterol
Hepato/2011; 5: 679-84.
6.
Reinisch W, et al. Adalimumab for
induction of clinical remission in
moderately to severely active
ulcerative colitis: results of a
randomized controlled trial. Gut 20
l l ; 60: 780-7.
7. Sandborn WJ,
et al. Adalimumab induces and
maintains clinical remission in
patients with moderate-to-severe
ulcerative colitis. Gastroenterolo9Y
2012; 142: 257-65.e1-3.
8.
Burness CB, Keating GM. Adalimumab:
a review of its use in the treatment
of patients with ulcerative colitis.
BioDruos 2013; 27: 247-62.
9.
Panacdone R, et al. Adalimumab
maintains remission of Crohn's
disease after up to 4 years of
treatment: data from CHARM and
ADHERE. Aliment Pharmacal Ther 2013;
38: 1236-47.
10. Viola F, et al.
Efficacy of adalimumab in
moderate-to-severe pediatric Crohn's
disease. Am J Gastroentero/ 2009;
104: 2566-71
11. Russell RK, et
al. A British Society of Pediatric
Gastroenterology, Hepatology and
Nutrition survey of the
effectiveness and safety of
adalimumab in children with
inflammatory bowel disease. Aliment
Pharmacal Ther 20ll; 33: 946-53.
12. Hyams JS, et al. Safety and
efficacy of adalimumab for moderate
to severe Crohn's disease in
children. Gastroenterology 2012;
143: 365-74.
Psoriasis
Adalimumab is used in
the treatment of plaque psoriasis
I. NICE. Adalimumab for the
treatment of adults with psoriasis:
Technology Appraisal Guidance 146
(issued June 2008). Available at:
http://www.nice.org.uk/nicemedia/pdf/TA146Guidance.pdf
(accessed 25/07/08)
2. Papoutsaki
M. et al. Adalimumab for the
treatment of severe psoriasis and
psoriatic arthritis. Expert Opin
Bioi Ther 2008; 8: 363-70.
3.
Traczewski P, Rudnicka L. Adalimumab
in dermatology. Br J Clin Pharmacol
2008; 66: 6 18-25.
4. Croom KF,
McCormack PL. Adalimumab: in plaque
psoriasis. Am J Clin Dermatol 2009;
10: 43-50.
5. Iaconi A, et al.
Psoriasis and its treatment with
adalimumab. Expert Opin Biol Ther
2010; 10: 1 3 3-52.
6. Leonardi
C, et al. Efficacy, safety and
medication cost implications of
adalimumab 40 mg weekly dosing in
patients with psoriasis 7. Saraceno
R, et al. Adalimumab in the
treatment of plaque-type psoriasis
and psoriatic arthritis. Expert Opin
Biol Ther 2013; 13: 1325-34.
Rheumatoid arthritis
Some
references to the use of
adalimumab in rheumatoid arthritis
(P-1 3.2) and juvenile idiopathic
arthritis
I.
Navarra-Sarabia F, et al. Adalimumab
for treating rheumatoid arthritis.
Available in The Cochrane Database
of Systematic Reviews; Issue 3.
Chichester: John Wiley; 2005
(accessed 13/06/08).
2. Cvetkovic
RS, Scott LJ. Adalimumab: a review
of its use in adult patients with
rheumatoid arthritis. BioDrugs 2006;
20: 293-311.
3. Chen Y-F, et al.
NHS Health Technology Assessment
Programme. A systematic review of
the effectiveness of adalimumab,
etanercept and infliximab for the
treatment of rheumatoid arthritis in
adults and an economic evaluation of
their cost-effectiveness (issued
November 2006). Available at:
http://www.hta.ac.uk/fullmono/mon1042.pdf
(accessed 31 11/08)
4. Mease PJ.
Adalimumab in the treatment of
arthritis. Ther Clin RiskManag 2007;
3: 1 3 3-48.
5. NICE. Adalimmnab,
ctanercept and infliximab for the
treatment of rheumatoid arthritis
(includes a review of technology
appraisal guidance 36): Technology
Appraisal Guidance 130 (issued
October 2007). Available at:
http://www .nicc.org.
uk/nicemedia/pdfiT A l30guidance.
pdf (accessed 03/ l l /08)
6.
Lovell DJ, et a!. Pediatric
Rheumatology Collaborative Study
Group. Pediatric Rheumatology
International Trials Organization.
Adalimumab with or without
methotrexate in juvenile rheumatoid
arthritis. N Eng! J Med 2008; 359:
810-20.
7. NICE. Adalimumab,
etanercept, infliximab, rituximab
and abatacept for the treatment of
rheumatoid arthritis after the
failure of a TNF inhibitor (part
review of NICE technology appraisal
guidance 36 and review of NICE
technology appraisal guidance 126
and 141 ): Technology Appraisal
Guidance 1 9 5 ( issued August
2010). Available at:
http://www.nice.org.uk/nicemedia/live/
1 3 1 08/504 1 3 / 5041 3 .pdf
(accessed 041 1 1 1 1 0 )
8.
Wiens A, et al. Meta-analysis of the
efficacy and safety of adalimumab,
etanercept, and infliximab for the
treatment of rheumatoid arthritis.
Pharmacotherapy 2 0 1 0; 30:
339-'53.
9. Poddubnyy D,
Rudwaleit M. Efficacy and safety of
adalimumab treatment in patients
with rheumatoid arthritis,
ankylosing spondylitis and psoriatic
arthritis. Expert Opin Drug Safety 2
0 l l ; 10: 655-73.
Spondyloarthropathies
References1-13 to the use of adali
mumab in ankylosing spondylitis,
axial spondyloarthritis, and
psoriatic arthritis
1. Simpson D,
Scott LJ. Adalimumab: in psoriatic
arthritis. Drugs 2006; 66: 1487-96.
2. McLeod C, et al. NHS Health
Technology Assessment Program -
Ada!imum<lb, etanercept and
infliximab for the treatment of
ankylosing spondylitis: a systematic
review and economic evaluation
(issued August 2007). Available at;
http://vvvvw.hta.ac.uk/fullmono/mon
1128.pdf (accessed 3 1 / 1 0/08)
3. Mease PJ. Adalimumab in the
treatment of arthritis. Ther Clin
Risk Manag 2007; 3: 1 3 3-48.
4.
Papoutsaki M, et al. Adalimumab for
the treatment of severe psoriasis
and psoriatic arthritis. Expert Opin
Biol 8: 363-70.
5. NICE.
Adalimumab, etanercept and
infliximab in ankylosing
spondylitis: Technology Appraisal
Guidance 143 (issued May 2008).
Available at: http:/ twww .nice.org.
uk/nicemedia/pdf/T A l43Guidance.pdf
(accessed 3 1 / I 0/08)
6. Mease
PJ, et al. Adalimumab for long-term
treatment of psoriatic arthritis:
2-year data from the Adalimumab
Effectiveness in Psoriatic Arthritis
Trial (ADEPT). Ann Rheum Dis 2009;
68: 702-7. van der Heijde D, et a!.
ATLAS Study Group. Adalimumab
effectiveness for the treatment of
ankylosing spondylitis is maintained
for up to 2 years; long-term results
from the ATLAS trial. Ann Rheum Dis
2009; 68: 922-9.
8. Poddubnyy DA,
Rudwaleit M. Adalimumab for the
treatment of psoriatic arthritis.
9. NICE. Etanercept, and adalimumab
for the treatment of psoriatic
arthritis (review of technology
appraisal guidance 1 04 and 1 2 5 ):
Technology Appraisal Guidance 199
(issued August 2010). Available at:
http://www.nice.org.uk/nicemediallive/
1 3 1 1 0/50422/50422.pdf (accessed
1 9 / l 0/lO)
lO. Poddubnyy D,
Rudwaleit M. Efficacy and safety of
adalimumab treatment in patients
with rheumatoid arthritis,
ankylosing spondylitis and psoriatic
arthritis. Expert Opin Drug Safety
2011; 10: 655-73.
l l . Sieper J,
et al. Efficacy and safety of
adalimumab in patients with
non-radiographic axial
spondyloarthritis: results of a
randomized placebo-controlled trial
(ABILITY-I). Ann Rheum Dis 2012.
Available at: doi: I 0 . 1 1 3
6/annrheumdis-2012-201766
12.
Burness CB, Deeks ED. Adalimumab in
non-radiographic axial
spondyloarthritis. Drugs 2012; 72:
2385-95.
13. Saraceno R, et al.
Adalimumab in the treatment of
plaque-type psoriasis and psoriatic
arthritis. Expert Opin Biol Ther 2 0
1 3; 13: 1 325-34.
Uveitis
Adalimumab has been tried
with some success in the treatment
of idiopathic uveitis 1.2 (P- 1 6 1
5 . I ). Uveitis can also develop as
a complication of other inflammatory
disorders such as rheumatoid
arthritis; treatment with adalimumab
may improve ocular symptoms in
addition to its effect on the
primary disorder.
1. Adalirnumab
therapy for childhood uveitis. .l
149: 572-5.
2. Hiester S, et al.
Adalimumab in the therapy of uveitis
in childhood. Br J Ophthalmol 2007;
91: 319-24.
Adverse Effects, Treatment, and
Precautions
Injection site
reactions including erythema,
itching, pain, and swelling are the
most common adverse reactions with
adalimumab; however, most reactions
are mild and do not result in drug
withdrawal. Other common reactions
include headache, rashes, back pain,
hypertension, paraesthesias,
increased alkaline phosphate levels,
and cough. Autoantibodies to
adalimumab have been detected.
References:
1. Burmester GR, et
al. Adalimumab: long-term safety in
23,458 patients from global clinical
trials in rheumatoid arthritis,
juvenile idiopathic arthritis,
ankylosing spondylitis, psoriatic
arthritis, psoriasis and Crohn's
disease. Ann Rheum Dis 2012.
Available at: doi: l 0. 1 l
36/annrheumdis- 20l l -2 0 I 244
Porphyria. The Drug Database for
Acute Porphyria, compiled by the
Norwegian Porphyria Center (NAPOS)
and the Porphyria Center Sweden,
classifies adalimumab as possibly
porphyrinogenic; it should be used
only when no safer alternative is
available and precautions should be
considered in vulnerable patients.1
2. The Drug Database for Acute
Porphyria. Available at:
http;//www.drugs-porphyria.org
(accessed 15 / ll / 11)
Interactions
Methotrexate is
reported to reduce the clearance of
adalimumab by up to 44%, but the
licensed product information for the
latter states that dosage adjustment
for either drug does not appear to
be necessary.
Pharmacokinetics
Adalimumab is reported to have
linear pharmacokinetics at usual
dosages. After subcutaneous
injection peak concentrations are
reached in about 3 to 8 days and
bioavailability is estimated to be
64%. The mean terminal half-life is
about 2 weeks. Adalimumab crosses
the placenta and is distributed into
breast milk.
Single-ingredient Preparations
Arg.: Humira; Austral.: Humira;
Austria: Humira; Belg.: Humira;
Braz.: Humira; Canad.: Humira;
Chile: Humira; China: Humira; Cz.:
Humira; Denm.: Humira; Fin.: Humira;
Fr.: Humira; Ger.: Humira; Gr.:
Humira; Trudexa; Hong Kong: Humira;
Hung.: Humira; Irl.: Humira; Israel:
Humira; Ital.: Humira; Jpn: Humira;
Malaysia: Humira; Mex.: Humira;
Neth.: Hurnira; Norw.: Humira; NZ:
Humira; Pol.: Humira; Port.: Humira;
Rus.: Humira (XyMHpa); S.Afr.:
Humira; Singapore: Humira; Spain:
Humira; Swed.: Humira; Switz.:
Humira; Turk.: Humira; UK: Humira;
Ukr.: Humira (X)TMHpa); USA: Humira;
Venez.: Humira.