Comparison Between Two Non-Halogenated Glucocorticoid

J Int Med Res (1981) 9, 239
Comparison Between Two Non-Halogenated
Glucocorticoid Ointments in Psoriasis
A Heijer, Department ofDermatology, Regional Hospital, Uddevalla, Sweden
G Hesser, Department ofDermatology, Regional Hospital, Uddevalla, Sweden
P Holm, Department ofDermatology, Regional Hospital, Uddevalla, Sweden
L Salde, Medical Department, AB DRACO/TIKA (a subsidiary to AB ASTRA, Sweden), Lund,
Sweden
Observations made in a controlled double-blind investigation of two nonhalogenated topical steroids, hydrocortisone-l l-butyrate (HCB) and
budesonide in thirty-six patients with psoriasis revealed a clear difference in
therapeutic effect between the two ointments, indicating that they belong to
different groups of topical steroids according to a classification accepted in
the Nordic countries. Budesonide had a good therapeutic effect in all the
patients studied, while, as a rule, HCB was clearly less effective.
Introduction
Most available topical corticosteroids have
side-effects limiting their use in the treatment
of chronic diseases or large areas of the skin.
Their commonest side-effects are local atrophy
of the skin and an adverse action on the
adrenal cortex. Corticoids for topical use are
divided into four groups according to their
potency (Agrup et at 1978). Since all strong
(Group III) and very strong (Group IV)
steroids hitherto used are halogen-substituted,
it has been assumed that a good antiinflammatory effect as well as side-effects are
related to the halogen substitution in the
steroid structure. Triamcinolone acetonide, a
halogenated corticosteroid, has caused severe
systemic side-effects (Keczkes et a11967, May
et at 1976). In humans this steroid is broken
Address for reprints:
Lars Salde, Medical Department, AB DRACO, P.O.B.
1707, S-221 01 Lund, Sweden
down only slowly in the liver (Ryrfeldt,
Andersson & Edsbacker 1980).
Efforts have therefore been made to
diminish the side-effects by modifying the
structure of the steroids in such a way as to
accelerate their biotransformation. The
purpose of such efforts has been to achieve a
maximum anti-inflammatory effect without
any accompanying increase in frequency or
severity of their side-effects. When
hydrocortisone-17-butyrate* (HCB) was
placed on the market it was described as a
potent steroid but, like weak steroids, to have
no side-effects (Yasuda 1975). However,
clinical experience has since shown it to
possess the same properties - effect and sideeffects - as Group II steroids.
The claim (Sneddon 1973) that the steroid
in question does not prevent healing of rosacea
*Locoid 0·1 %, Gist-Brocades, Delft, Holland
0300-0605/81/040239-09 $02·00
©Cambridge Medical Publications Limited
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240
The Journal ofInternational Medical Research
and perioral dermatitis has been withdrawn
(Sneddon 1980).
A very potent non-halogenated steroid,
budesonide", has been synthesized by
DRACO (Thalen & Brattsand 1979). In
double-blind comparisons with established
Group III steroids budesonide has proved to
have a very good effect on psoriasis and other
dermatoses susceptible to steroid therapy
(Fredriksson & Salde, Lassus & Salde). Once
absorbed by the skin this steroid is quickly
broken down (Ryrfeldt et al 1980). It is well
tolerated by the patient and 'safe' even after
long use in the treatment of psoriasis (Bleeker
et aI1980).
This paper concerns a double-blind
comparison of non-halogenated steroids, HCB
and budesonide, both in the form of ointments.
Treatment was continued for 4 weeks and the
lesions were examined before the beginning of
the trial, after treatment for 2 weeks, and at the
end of the trial. The trial was carried out in the
winter of 1977-1978. Informed verbal consent
was obtained from all the patients before the
trial.
The results of treatment were assessed
according to a 5-grade scale (0-4), where 0
denotes absence of symptoms and 4 very
severe symptoms.
The symptoms assessed were itching,
excoriation, scaling, papules, induration and
erythema.
Notes were also made of any 'clinical'
healing and of the side of the body where the
lesions had responded better to the steroid
treatment.
Every time the out-patients re-visited the
clinic they were asked whether they had
noticed any side-effects, and their answers
were entered in their record sheets. The lesions
treated were photographed every time their
severity was assessed.
Materials and Methods
Thirty-two patients were divided into two
groups. One group was treated once a day; the
other, twice a day. The former group consisted
of seventeen patients (six women and eleven
men with a mean age of 46 years); the latter
group consisted of fifteen patients (seven
women and eight men with a mean age of 56
years).
The patients were selected in such a way as
to include various forms of psoriasis, such as
psoriasis nummuIaris and guttata. To facilitate
detection of any difference in effect between
the two ointments it was decided to use a
double-blind, right versus left comparison of
the effects on symmetrically distributed lesions
or affected patches of equal severity. This
made it necessary to exclude four of the thirtysix patients initially selected.
Throughout the trial one of the steroid
ointments was applied to a selected lesion or
affected patches on one side of the body, and
the other ointment to a corresponding lesion or
patches on the other side of the body (Wilson
1976).
The patients treated twice a day were inpatients and the ointment was applied under
the observation of the nurse in charge of the
ward. The other group consisted of outpatients who were instructed to use the
ointment twice a day and to spread it out in a
thin layer. No other form of treatment of the
psoriasis was allowed during the trial.
"Preferid 0·025%, AB Tika, Lund, Sweden
Results
The results noted in out-patients are
summarized in Tables 1 and 2; those in the inpatients, in Tables 3 and 4.
It is clear from the Tables that in both the
out-patients and the in-patients budesonide
had a significantly better effect than HCB on
scaling, induration and erythema. In the outpatients, who used the ointments once a day,
also the papules responded significantly
better on the side treated with budesonide. In
addition, both the doctors and the patients
thought budesonide to be preferable (Tables 2
and 4).
The effects of treatment (mean values) on
the individual symptoms after treatment for 2
weeks and after 4 weeks can be directly
compared in Figures 1 and 2. Already after 2
weeks budesonide had a significantly better
effect on all the four symptoms studied
(P" 5% for scaling, induration and erythema
in out-patients treated once a day and p <;; 5%
for scaling and induration in in-patients treated
twice a day) than had hydrocortisone-17butyrate after treatment for 4 weeks (Student's
t-test), The results show that the most
important effects from the patient's point of
view, quick alleviation of the symptoms and
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A Heijer et al
241
Table 1
Individual symptoms after appUcation of ointments once a day for 2 and 4 weeks in out-patients
2 Weeks
Budesonide better
HCB better
No difference
P =B
4 Weeks
Budesonide better
HCB better
No difference
p= B
A
Itching"
Excoriation A
Scaling
2
0
12
0·5
3
1
3
0·6
10
3
0
13
0
3
0
11
0·25
0
7
0·002"
4
4
0·25
0·0002···
Papules A
Induration
Erythema
7
0
8
0·015·
11
0
6
0·001···
0
8
0·004··
9
13
0
6
0·004··
0
4
0·0002"·
9
12
0
5
0·0004···
Some patients did not have this symptom
Bp-values denote two-sided sign test
Table 2
Ointment preferred after appHcation once a day for 2 and 4 weeks In out-patients
A
Budesonide
HeB
No difference
p-value"
2 Weeks
Patient
Doctor
13
11
0
0
4
6
0·0002·"
0·001"·
4 Weeks
Patient
Doctor
15
15
0
0
2
2
0"·
0"·
p-values denote two-sided sign test
acceleration of healing, can be achieved with
budesonide.
The difference in response to the two
ointments was most often obvious. The
smallness of the number of cases in which the
therapeutic effects of both ointments were
considered equal underlines that the difference
in response of the lesions was otherwise
clinically important. This is apparent from
Figures 3-11, which clearly illustrate the
difference in the results of treatment of,
respectively, psoriasis guttata (Figures 3-8)
and psoriasis nummularis (Figures 9-11).
Figures 6-8 show that HCB had no
demonstrable effect on the lesions in psoriasis
nummularis, and Figures 9-11 show that
though it had some, but not satisfactory, effect,
it was not comparable to that of budesonide.
One patient reported a sensation of burning
after application of both ointments and two
experienced local itching of the lesions treated
with HCB. In one case the course after the end
of treatment was both unexpected and
interesting and is briefly described below.
A 45-year-old woman who had had
psoriasis nummularis/discoides for 10 years
and had been treated for 4 weeks with both
ointments was seen again 11 weeks after the
end of the treatment. Her condition before and
after 4 weeks' treatment is given in Figures 12
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The Journal ofInternational Medical Research
242
Table 3
IDdividualsymptoms after application of ointments twice a day for 2 and 4 weeks in in-patients
2 Weeks
Budesonide better
HCB better
No difference
p= 8
4 Weeks c
Budesonide better
HCB better
No difference
P =8
A
Itching"
Excoriation A
Scaling
Papules A
Induration
Erythema
0
0
10
1
0
5
-
-
14
0
1
0·0002···
5
0
2
0·06
14
0
1
0·0002···
9
0
6
0·004"
3
0
2
0·25
10
0
4
0·002··
4
1
1
0·37
12
7
0
7
0·015·
1
0
9
-
0
2
0·0004···
Some patients did not have this symptom
8 p-values denote two-sided sign test
C
One patient did not return for 4-week review
Table 4
Ointment preferred after application twice a day for 2 and 4 weeks in in-patients
A
Budesonide
HCB
No difference
p-value"
2 Weeks
Patient
Doctor
12
14
1
0
2
1
0·003"
0·0002"·
4 Weeks
Patient
Doctor
11
12
0
0
3
2
0·001·"
0·0004·"
p-values denote two-sided sign test
8 One patient did not return for 4-week review
and 13. The lesion that had been treated with
HCB during the trial and that had not
responded satisfactorily to it was at least just
as severe as it had been before the trial (Figure
14). In contrast, the lesion treated with
budesonide had continued to improve in that
the residual erythema demonstrable at the end
of the trial had completely disappeared.
During the 11 weeks' interval the patient had
received no treatment for psoriasis at all.
Discussion
HCB has recently been classified (Agrup et al
1978) as a Group 11 steroid. The findings
made in the present trial corroborate this
classification and at the same time show that
budesonide is the first non-halogenated Group
III steroid, an observation supported also by
other investigations (Fredriksson & Salde,
Lassus & Salde, Bleeker et aI1980).
The results of treatment vary with the
composition, i.e. all the ingredients, of the
product. The two ointments studied differ in
composition of their bases in that budesonide
has a classical occlusive base (vaseline, white
wax, paraffin oil, propylene glycol), while
HCB has a Plastibase'" (paraffin oil in a
polyethylene skeleton). But it is unlikely that
the difference in effect of the two ointments
can be explained by their difference in base.
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A Heijer et al
243
TREATMENT ONCE/DAY
BUDESONIDE
- - HYDROCORTISONE-17-BUTYRATE
4
ITCHING
4
INDURATION
N-14
N-17
3
3
2
2
------- ------L
----J
0
0
1
0
2
3
1
0
4
2
3
SCALING
N-17
4
4
~EEKS
~EEKS
4
ERYTHEMA
N-17
3
3
--- --- --- ------L
2
--------J
2
--- ------
----L
-- -- J
I
o .......__
....L._ _---L
o
2
........._ _....J
3
..
o L..-_ _
o
..L...-_ _...L-_ _....L-_ _..J
~EEKS
2
3
..
~EEKS
Fig 1 Individual symptoms as function ojduration of'treatment (mean ± S.E.M.) with application once a day
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244
The Journal ofInternational Medical Research
TREATMENT TWICE/DAY
BUDESONIDE
- - HYDROCORTISONE-17-BUTYRATE
4
ITCHING
4
INDURATION
N-10
N-14
3
3
2
2
0
0
2
0
4
3
4
WEEKS
SCALING
N-14
3
4
WEEKS
ERYTHEMA
N-14
4
3
3
<,
<,
<,
<,
2
2
0
. . . . ..::r
---
2
-...-...
-...
--J
-"'-...J
---J"
o ~--.&----..&----.........- -.....
o
2
3
4
o "------.........- -........- - - - - - -....
WEEKS
WEEKS
o
Fig 2 Individual symptoms as function ofduration oftreatment (mean
2
3
4
± S.E.M.) with application twice a day
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A HeQeret aI
245
Fig J SllItru bt(fore~
FigB Statru qftg treatmmt/or41lWk1
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The Journal ofInternational Medical Research
246
Fial2 Statui before treatment
FIIIO StGIIIIqftu tr«IlnIent/or 2 weeki
Fia 13 Statui qftu trwJtrMrIt/or -# weeki
Fiall Statui qftu trwJtrMrIt/or -# weeki
Fig 14 SlGlIII JJ weeb qftu end oj'tretJtm#II
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247
A Heijer et al
The present investigation does not warrant Fredrlksson T &; Salde L
double-blind trial of budesonide and betamethasoneany conclusion as to whether the balance A
17, 21-dipropionate in psoriasis. (In manuscript)
between the therapeutic effect and adverse Keczkes K, Fraln-BeD W, Honeyman A L &; Sprunt G
effects of budesonide is more favourable than (1967) The effect on adrenal function of treatment of
eczema and psoriasis with triamcinolone acetonide.
that of other corticosteroids of corresponding British Journal ojDermatology 79, 475
strength. Other investigations, however, have Lassus A &; Salde L
double-blind comparison of two topical steroids in
shown once budesonide has penetrated the A
psoriasis and eczemas: Budesonide 0·025% ointment
dermis, it is quickly broken down (Ryrfeldt et and betamethasone-17-valerate 0·1 % ointment. (In
al 1980), which may imply that its systemic manuscript)
May P, Stein E J, Ryter R J, Glrsb F S, Mlcbel B &; Levy
effect is less than that of other very potent RP
steroids. This assumption is supported by the (1976) Cushing syndrome from percutaneous absorption
observation that budesonide is well tolerated of triamcinolone cream. Archives of Internal Medicine
(Chicagol136,612
by the patients and that its use is safe even in Ryrfeldt :t,Andersson P &; Edsbiicker S
long-term treatment of psoriasis (Bleeker et al (1980) Liver and skin biotransformation of
g1ucocorticosteroids in hairless mouse, rat and man. In:
1980).
'Abstracts' the 22nd Nordic Conference on
Acknowledgement
Photographs by Kjell Tornqvist.
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