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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.

STUDY Calcipotriol/
Betamethasone
dipropionate
O.D.
Betamethasone
dipropionate
O.D.
Calcipotriol
O.D.
Calcipotriol
scalp solution
B.I.D.
Vehicle
O.D.
Buckley, et al.31
(n=218)
83.3% 74.6%      
Jemec, et al.32
(n=1505)
71.2% 64.0% 36.8%   22.8%
van der Kerkhof, et al.33
(n=1415)
68.4% 61.0% 43.4%    
Kragballe, et al.34
(n=312)
68.6%     31.4%  
Luger, et al.36
(n=869)
55.7%   31.8%    
Tyring, et al.37
(n=175)
71.9%       40.5%
Table 1: Percent of patients with Investigator Global Assessment of absent/very mild at 8 weeks


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%.

STUDY Patients with at
least 1 AE
Patients with 1 AE
on calcipotriol or
vehicle
Patients with
perilesional AEs
Adverse Drug Reactions
Buckley, et al.31 74.6% --------- 10.3% Xamiol®
vs. 10.0% betamethasone
8.l4% Xamiol® vs.
10.9% betamethasone
Jemec, et al. 34.4% Xamiol®
vs. 34.9%
betamethasone
(p=0.91)
46.2% calcipotriol
(p=0.0014) vs.
40% vehicle
(p=0.24)
4.7% Xamiol® vs.
5.3% betamethasone
vs. 13.2%
calcipotriol vs.
13.3% vehicle
7.9% Xamiol® vs.
8.4% betamethasone vs.
19.5% calcipotriol vs.
15.6% vehicle
van der Kerkhof, et al.33 38.7% Xamiol®
vs. 41.0%
betamethasone
(p=0.43)
46.1% calcipotriol
(p=0.04)
6.2% Xamiol® vs.
5.8% betamethasone
vs. 12.8%
calcipotriol
9.6% Xamiol® vs.
8.8% betamethasone vs.
18.4% calcipotriol
Kragballe, et al.34 34.5% Xamiol® 56.7% calcipotriol
scalp solution
(p<0.001)
3.4% Xamiol® vs.
19.2% calcipotriol
scalp solution
(p<0.001)
3.4% Xamiol® vs.
26.9% calcipotriol scalp
solution (p<0.001)
Luger, et al.36 66.8% 71.9% calcipotriol
(p=0.11)
11.9% Xamiol® vs.
21.6% calcipotriol
(p<0.001)
17.2% Xamiol® vs.
29.5% calcipotriol (p<0.001)
Tyring and Bibby37 36.7% Xamiol® vs.
34.2% vehicle
--------- 3.1% Xamiol® vs.
2.6% vehicle
6.3% Xamiol® vs.
7.9% vehicle
Table 2: Adverse events reported for studies comparing Xamiol® with other treatments.


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.

References

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  32. Jemec GB, Ganslandt C, Ortonne JP, et al. A new scalp formulation of calcipotriene plus betamethasone compared with its active ingredients and the vehicle in the treatment of scalp psoriasis: a randomized, double-blind, controlled trial. J Am Acad Dermatol 59(3):455-63 (2008 Sep).
  33. van der Kerkhof PC, Hoffmann V, Anstey A, et al. A new scalp formulation of calcipotriol plus betamethasone dipropionate compared with each of its active ingredients in the same vehicle for the treatment of scalp psoriasis: a randomized, double-blind, controlled trial. Br J Dermatol 160(1):170-6 (2009 Jan).
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  35. Ortonne JP, Tan J, Nordin P, et al. Quality of life of patients with scalp psoriasis treated with calcipotriene plus betamethasone dipropionate gel compared to calcipotriene solution. J Am Acad Dermatol 58(2 Suppl 2):AB134 (2008 Feb).
  36. Luger TA, Cambazard F, Larsen FG, et al. A study of the safety and efficacy of calcipotriol and betamethasone dipropionate scalp formulation in the long-term management of scalp psoriasis. Dermatology 217(4):321-8 (2008).
  37. Tyring S, Bibby A. Calcipotriene/betamethasone dipropionate gel compared to gel vehicle in treatment scalp psoriasis in Hispanic/Latino and black/African American patients. J Am Acad Dermatol 58(2 Suppl 2):AB125 (2008 Feb).

In this issue:

  1. Treatments for Scalp Psoriasis with Emphasis on Calcipotriol Plus Betamethasone Dipropionate Gel (Xamiol®)
  2. Use of Tacrolimus Ointment in Vitiligo Alone or in Combination Therapy
  3. Update on Drugs and Drug News - May 2009