Treatments for Scalp Psoriasis with Emphasis on Calcipotriol Plus Betamethasone Dipropionate Gel (Xamiol®)

L. C. Guenther, MD, FRCPC

The Guenther Dermatology Research Centre, London, ON, Canada

ABSTRACT

Scalp psoriasis occurs in 50%-75% of patients with plaque psoriasis. It may be the only area of the body affected, or it may be associated with disease elsewhere, including psoriatic arthritis. Most cases are treated topically, usually with steroids and/or calcipotriol. In 2008, Health Canada and the US FDA approved a stable, once-daily 2-compound gel containing calcipotriol and betamethasone dipropionate (Xamiol®, LEO Pharma; Taclonex Scalp®, Warner Chilcott). This once-daily therapy improves patient quality of life with a quick onset of action and greater efficacy than monotherapy with either ingredient or twice daily treatment with calcipotriol 0.005% (Dovonex®, LEO Pharma) scalp solution. The gel vehicle was developed for ease of use, improved cosmetic acceptability and absorption on the scalp. By 2 weeks, approximately 60%, and by 8 weeks, approximately 70% of patients have controlled disease (i.e., absent or very mild disease). At 8 weeks, the calcipotriol and betamethasone dipropionate gel formulation has a safety profile comparable with betamethasone dipropionate and is associated with significantly fewer adverse events than
calcipotriol. Xamiol® may be safely used for up to 52 weeks. No cases of atrophy, striae, or steroid purpura were noted in two 52-week studies.

Key Words:
calcipotriol, betamethasone dipropionate, steroid, vitamin D analogue, psoriasis, scalp psoriasis, fixed combination
therapy

Scalp Psoriasis

Psoriasis affects approximately 2% of the population,1
and in 50%-80% of cases, the scalp is affected.² Scalp
involvement may occur in isolation, with plaque psoriasis
located elsewhere (most common), or with erythrodermic,
pustular or guttate psoriasis, and/or psoriatic arthritis.³ Single
or multiple, erythematous, pruritic, scaly plaques may occur
anywhere on the scalp. The entire scalp may be affected and
lesions may spread onto the forehead and behind the ears.
Quality of life can be severely compromised, particularly if
lesions are visible, scales fall onto clothes, and when pruritus
is intense. Hair loss due to telogen effluvium may rarely
occur.⁴ Scaling and hair, particularly with very thick hair,
may be obstacles to medications reaching the scalp.

Current Treatments for Scalp Psoriasis

Treatment is almost always topical, although systemic and
biologic therapy may be necessary, particularly if there is
also extensive psoriasis elsewhere on the body.3 Once-daily,
efficacious treatments have been associated with greater
adherence.⁵

Topical steroids are the most widely used treatment. They
are available in a number of formulations including lotions, solutions, gels, sprays, foams, shampoos, oils, ointments,
and creams. In a randomized controlled trial, superpotent
clobetasol propionate shampoo (Clobex®, Galderma) was
shown to control (i.e., clear/almost clear) the disease in
42.1% of the patients (compared with 2.1% using the
vehicle).⁶ In a double-blind, vehicle controlled study, 26% of
the patients showed complete clearance vs. only 1% of the
patients applying the vehicle.⁷ Foams are well tolerated and
efficacious. Of the patients in clinical trials 72%-74% were
controlled with betamethasone valerate⁸ or clobetasol foam.⁹
Salicylic acid may be added for its keratolytic effects (e.g.,
Diprosalic® lotion, Schering Plough).^3,10

The unpleasant smell, yellow staining of white or grey hair,
and mutagenic potential limit the use of tars.¹¹

Calcipotriol (Dovonex®, LEO Pharma), a topical vitamin
D derivative, may be safely used for 52 weeks.¹² One study
showed that twice daily application has similar efficacy
to 1% betamethasone valerate,¹³ although other studies
showed that it was significantly less effective than 0.1%
betamethasone 17-valerate solution,¹⁴ and 0.05% clobetasol
propionate shampoo.¹⁵

Some patients are treated with a twice-daily application of
calcipotriol and corticosteroids to try to improve efficacy
and tolerability. However, mixing commercially available
topical steroids and calcipotriol is not advised, since the pH
of the resultant mixture would be different and most likely
both components would be inactivated.

Two small studies showed that a stable topical ointment
containing calcipotriol and betamethasone dipropionate
(Dovobet®, LEO Pharma) is efficacious.^16,17 However, the
ointment base is generally not well accepted for scalp use,
since it makes the hair greasy and is difficult to wash out of
long hair.

Xamiol®, the Compound

Xamiol® is a lipophilic gel specially formulated for the
scalp. It contains the same active ingredients as Dovobet®
ointment, namely calcipotriol 0.005% and betamethasone
dipropionate 0.05%.¹⁸ This shear thinning gel sets when at
rest and gets thinner when shaken. It has 2 year stability at
room temperature, but should be used within 3 months of
opening.¹⁹ Systemic absorption is low.¹⁹

Mechanism of Action

Calcipotriol binds to the vitamin D receptor, then acts
as a heterodimer with the retinoid X receptor (RXR),²⁰
normalizing differentiation and proliferation. It also reduces
CD45RO+ and T suppressor cells, and induces a Th1 to Th2
switch.^21-24

Betamethasone dipropionate is a potent topical steroid. In
the cytoplasm, steroids bind to glucocorticoid receptors,
then rapidly translocate to the nucleus where they inhibit or stimulate genes that regulate inflammation.25
As a consequence, the production of cytokines, such as
interleukin–1 and –8, tumor necrosis factor alpha, and
gamma interferon are inhibited; nitric oxide, prostaglandins,
and levels of leukotrienes are reduced.^23,26,27 Corticosteroids
can also regulate keratinocyte differentiation.²⁸ Both
vitamin D and corticosteroids can increase the number of
T regulatory cells that are diminished in psoriatic skin.^29,30

Clinical Efficacy of Xamiol®

This formulation has a quick onset of action and is an
effective long-term treatment. In the phase II trial (n=218),31
after 2 weeks, the total sign score (TSS = redness score +
thickness score + scaling score; range 0-12) decreased by
4.49 in the Xamiol® arm, and by 3.75 in the betamethasone
arms (p=0.005). Moreover, 67.6% of the Xamiol® group
compared with 52.7% in the betamethasone group were
clear/almost clear (p=0.025). At 8 weeks, the TSS was
reduced by 5.33 for the Xamiol® group vs. 4.76 for the
betamethasone arm (p=0.042); 83.3% of patients in the
Xamiol® group vs. 74.6% using betamethasone showed an
absence of disease or very mild disease.

The 2 phase III, international, multicenter, randomized,
blinded pivotal trials involved almost 3,000 patients and
showed that Xamiol® was more efficacious than its individual
ingredients.^32,33 (Table 1)

Jemec et al.32 reported a reduction of 70.8% in TSS in the
Xamiol® group, 57.7% in betamethasone dipropionate
(p=0.12) group, 49.0% in the patients using calcipotriol
(p<0.0001), and 35.6% using the vehicle (p<0.0001). The
Investigator Global Assessment (IGA) was “absent/very mild” in 71.2% of the patients who were treated with
Xamiol® vs.:

• 64.4% of those treated with betamethasone dipropionate (odds ratio [OR] 1.41, 95% confidence interval [CI]: 1.08-1.83, p=0.011)
• 36.8% of those treated with calcipotriol (OR 4.13, 95% CI: 3.00-5.70, p<0.0001)
• 22.8% of patients treated with the vehicle (OR: 8.65, 95% CI: 5.52-13.56, p<0.0001).

The onset of action was fast; at 2 weeks, 57.5% had
absent/very mild disease on Xamiol® compared with 47.1%
on betamethasone, 18.8% on calcipotriol, and 11.8% on
vehicle. The amount of study medication used during the
entire study was less for Xamiol® (139.1gm vs. 159.5gm for
betamethasone, 155.4gm for calcipotriol, and 176.4gm for
vehicle. The average weekly quantity of study medication
used was 17-22gm/week.

In a study by Kragballe et al., once-daily Xamiol® was
compared with twice daily Dovonex® scalp solution
(n=312).34 More than twice as many patients using Xamiol®
had controlled disease (i.e., absent/very mild; 68.6% vs.
31.4%). At 8 weeks, 56.3% of those whose condition was
very severe had controlled disease with Xamiol®, but none did on calcipotriol. In common with Jemec’s trial, a quick
onset was noted; at week 2, 49% on Xamiol® compared with
38.4% on steroids, and 15.7% on calcipotriol had absent/
very mild disease. Significant improvements in quality of
life, as measured by the short form-36 (SF-36) questionnaire,
were noted in the mental component at weeks 2, 4, and
8, but only at week 8 for calcipotriol scalp solution.³⁵ In
addition, the amount of improvement in the Skindex 16 was
approximately twice as great with Xamiol®.

Two 52-week studies assessed long-term management.^36,37 In
the first study, disease was absent/very mild/mild at 92.3%
of the visits in the Xamiol® arm vs. 80% in the calcipotriol
arm (p<0.0001).36 The withdrawal rate due to unacceptable
treatment efficacy was higher in the calcipotriol arm
(11.6% vs. 3.3%). The second long-term study (n=175) was
conducted in patients who were Hispanic/Latino (56%) or
African-American (44%).³⁷ In the initial 8-week placebo
controlled portion, significantly more patients on Xamiol®
than vehicle had controlled disease (71.9% vs. 40.5%,
p<0.001). In patients treated with Xamiol® from the onset,
the median number of visits in which patients had clear,
minimal or mild disease was 100%.

Patient Information

The Xamiol® bottle should be shaken. Then part hair to
expose the affected area of the scalp, then apply to dry skin
and gently rub in. Wash hands after applying. To remove
any excess gel vehicle from the hair, a mild, unmedicated
shampoo should be applied to dry hair and left on for a few
minutes. Then the hair should be washed normally. A second
shampooing may be required.¹⁸

Safety of Xamiol®

There were no significant changes in serum calcium, skin
atrophy, or striae in any of the trials. Table 2 summarizes
adverse events in the phase II and pivotal phase III trials.
A 52-week Xamiol® vs. calcipotriol study by Luger et al.36
showed similar results, although there were no differences in
the rates of AEs possibly related to long-term corticosteroid
use (e.g., rosacea, folliculitis, acne; 2.6% Xamiol® vs. 3.0%
corticosteroids). In the Hispanic/Latino/African-American
study, the Xamiol® and vehicle groups had similar AE rates
(36.7% and 34.2, respectively), adverse drug reactions (6.3%
and 7.9%, respectively) and perilesional/lesional adverse
events (3.1 and 2.6%, respectively) at 8 weeks.³⁷

Conclusion

Xamiol® is a fast-acting, very efficacious, safe, oncedaily
treatment for scalp psoriasis ranging from mild to
very severe. It is more efficacious than calcipotriol in the
same base, or as the marketed solution (Dovonex® scalp
solution), betamethasone dipropionate, or the gel vehicle.
Approximately 60% of patients achieve absent or very
mild disease after only 2 weeks of therapy, and 70% after 8
weeks. The safety profile is similar to that of betamethasone
dipropionate and better than calcipotriol. Two 52-week
studies have shown that Xamiol® can be safely used longterm.
No cases of atrophy, striae, or senile purpura were
noted in any of the studies.

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