hydrea and infliximb

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Journal of Dermatological Treatment
ISSN: 0954-6634 (Print) 1471-1753 (Online) Journal homepage: http://www.tandfonline.com/loi/ijdt20
Successful treatment of recalcitrant psoriasis with
a combination of infliximab and hydroxyurea
J E Gach & J Berth‐Jones
To cite this article: J E Gach & J Berth‐Jones (2003) Successful treatment of recalcitrant
psoriasis with a combination of infliximab and hydroxyurea, Journal of Dermatological
Treatment, 14:4, 226-228
To link to this article: http://dx.doi.org/10.1080/09546630310015386
Published online: 12 Jul 2009.
Submit your article to this journal
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Successful treatment of recalcitrant psoriasis with a
combination of infliximab and hydroxyurea
Introduction
We report the use of a combination of the tumour
necrosis factor a(TNF a) inhibitor infliximab and
hydroxyurea to achieve control of disabling psoriasis
and psoriatic arthritis. A 49-year-old white Caucasian
female had suffered from severe psoriasis since the
age of 14. Additional features of her medical history
included hypertension, hypercholesterolaemia, depres-
sion and diet controlled non-insulin dependent diabetes
mellitus. Her alcohol consumption was estimated at
30 units a week. She was taking atenolol 100 mg,
paroxetine 20 mg, fluvastatin 20 mg, ibuprofen 200 mg
and indomethacin 50 mg daily. Previous treatments
employed over the years for her skin disease included
vitamin D analogues, topical steroids, dithranol, crude
coal tar, narrow band UVB and bath PUVA in various
combinations. Acitretin had been used for 4 years
but was complicated by hyperlipidaemia. The use of
ciclosporin was precluded by the presence of hyperten-
sion and hypercholesterolaemia. The patient did not
wish to reduce her alcohol intake to enable her to
use methotrexate. Her skin disease proved resistant to
conventional therapy, as her psoriatic plaques would
only become thinner but never actually disappear
from her body. Increasingly, the patient was becoming
depressed about the impairment of her quality of life
resulting from the recalcitrant psoriasis affecting more
than 50% of her skin. She was also experiencing
increasing morning stiffness and pain in the small
joints of her hands and feet which was not relieved
by increasing doses of non-steroidal anti-inflammatory
drugs.
Patient and methods
She was commenced on hydroxyurea 500 mg daily and
the dose was increased to 1 g daily. Although somewhat
improved the psoriasis was still not well controlled after
eight weeks on this dose. She was then commenced
on infliximab. An initial infusion was given at the dose
of 400 mg (5 mg/kg body weight). The patient noted
a very prompt improvement in her arthralgia and
psoriasis. She commented that the joint stiffness was
reduced 24 hours after the infusion. Her symptoms
continued to improve over the next two weeks and her
psoriasis cleared except for a small plaque over the left
elbow.
During the past 12 months the patient has remained
on hydroxyurea 1 g daily combined with infliximab
infusions repeated at three monthly intervals to main-
tain satisfactory control of her psoriasis and psoriatic
arthritis. She has not reported any side-effects from
this treatment regimen and her full blood count has
remained normal.
J E Gach and J Berth-Jones
Department of Dermatology, University
Hospitals Coventry and Warwickshire
NHS Trust, Coventry CV2 2DX, UK
We report the use of a combina-
tion of the tumour necrosis factor
a(TNF a) inhibitor infliximab and
hydroxyurea to achieve control of
disabling psoriasis and psoriatic
arthritis. Our patient had psor-
iasis that proved resistant to
conventional therapy including
vitamin D analogues, topical ster-
oids, dithranol, crude coal tar,
narrow band UVB, bath PUVA
and acitretin. She subsequently
responded to hydroxyurea 1 g
daily combined with infliximab
infusions repeated at three
monthly intervals which led to
satisfactory control of her psor-
iasis and psoriatic arthritis. She
has not reported any side-effects
from this treatment regimen
and her full blood count has
remained normal. (J Dermatol
Treat (2003) 14: 226–228)
Received 9th May 2003
Accepted 24th June 2003
Keywords: Hydroxyurea — Infliximab — Recalcitrant psoriasis
Correspondence:
Dr J E Gach, Department of Dermatology, Selly Oak Hospital, Raddlebarn
Road, Birmingham B29 6JD, UK. E-mail: [email protected]
Journal of Dermatological Treatment (2003) 14, 226–228
#2003 Journal of Dermatological Treatment. All rights reserved. ISSN 0954-6634
DOI: 10.1080/09546630310015386
226
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Discussion
Psoriasis is a chronic cutaneous inflammatory disease
characterised by hyperproliferation of keratinocytes
and infiltration of activated T lymphocytes into the
epidermis which are responsible for the release of mul-
tiple cytokines. These cytokines are predominantly of
the Th 1 profile and include IL-2, interferon-c, IL-12
and TNF-a. The latter is present in high levels in pso-
riatic plaques and serum of patients with psoriasis as
well as in the joint fluid of patients with psoriatic
arthritis.
1
At the cellular level, TNF-astimulates expression of
ICAM-1 on keratinocytes and their production of IL-8
and transforming growth factor-a, and E-selectin on
endothelial cells.
2
This suggests that TNF-aplays a role
in pathogenesis of psoriasis by activating T lymphocytes,
enhancing the infiltration of T lymphocytes into the
epidermis and augmenting keratinocyte proliferation.
TNF-ainhibitors therefore have the potential to improve
psoriasis by reducing inflammation and normalisation
of keratinocyte proliferation.
Infliximab is a chimeric (mouse-human) monoclonal
antibody that binds to TNF-awith high affinity and
neutralises the biological activity of this cytokine.
3
Infli-
ximab is already licensed for treatment of rheumatoid
arthritis and Crohn’s disease in the UK.
In a randomised double-blind placebo-controlled trial
of infliximab in patients with moderate or severe psoria-
sis 17 out of 22 patients were clear or almost clear of
their disease at week 10 following 3 infusions.
4
Another
recent study by Schopf et al also using infliximab as
monotherapy confirmed the efficacy of this treatment for
severe psoriasis. However the psoriasis tended to relapse
about 8 weeks after the last infusion.
5
Infliximab is not a human monoclonal antibody and
therefore has a potential for inducing neutralising anti-
bodies when used on a long-term basis. It has been
shown that concomitant use of infliximab and low-dose
methotrexate (MTX) of 7.5 mg weekly for the treatment
of rheumatoid arthritis diminished the appearance of
human antichimeric antibodies and also potentiated
its clinical response.
6
The treatment is well tolerated
in the short term, although long-term safety profile of
infliximab needs to be studied. Infliximab was reported
to be used successfully in combination with MTX in
treatment of recalcitrant psoriasis.
7, 8
Our patient was treated with a combination of infli-
ximab with hydroxyurea. The latter drug is a hydro-
xylated derivative of urea and is an antineoplastic agent
that inhibits DNA synthesis and repair.
9
Hydroxyurea
is known to be effective as a monotherapy for severe
psoriasis in doses ranging from 0.5 to 1.5 g daily.
Layton et al found that 52 of 85 patients with extensive
chronic plaque psoriasis who were unresponsive to
conventional topical therapy achieved a satisfactory
remission during treatment with hydroxyurea without
significant adverse effects.
12
Therapy was discontinued
in 33 patients due to inadequate response or adverse
effects. In our patient the use of hydroxyurea in com-
bination with anti-TNFaagent appeared to produce a
beneficial effect by promptly inducing and maintain-
ing clearance of psoriasis and resolution of the sym-
ptoms of psoriatic arthritis. This combination therapy
for refractory psoriasis has not previously been des-
cribed. Hydroxyurea is known to have the potential to
suppress B cell responses
10, 11
and may therefore inhibit
the antibody response to infliximab in the same way
as methotrexate, as well as demonstrating a synergistic
therapeutic effect on the psoriasis.
Conclusion
This combined regimen may prove to be a useful new
treatment option for patients suffering from severe
psoriasis and/or psoriatic arthritis.
References
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