Introduction

Combining keratolytic agents or topical corticosteroids with antifungals has been shown to be effective in treating certain hair and scalp conditions. In vitro studies and pilot clinical study of ciclopirox olamine (CPO) and zinc pyrithione (ZP) (1.5% CPO/1% ZP) have showed synergistic inhibitory and fungicidal effect on Malassezia globosa and Malassezia restricta species, with a higher efficacy compared to 2% ketoconazole in patients with scalp seborrhoeic dermatitis.

Aim

To evaluate the efficacy of a shampoo containing the 1.5% CPO/1% ZP association compared to the vehicle shampoo and to 2% ketoconazole foaming gel in the treatment of scalp seborrhoeic dermatitis.

Patient Profile

Male or female patients aged 18 years  and more, presenting a clinically diagnosed scalp seborrhoeic dermatitis including scales, erythema, and pruritus.

Methods

• Multicentre, controlled, single blinded, randomised clinical study.
• The study enrolled 189 patients , randomly assigned to following treatments
  • CPO/ZP (1.5% CPO/1% ZP) shampoo twice a week for 28 days (n=63),
  • 2% ketoconazole foaming gel twice a week for 28 days (n=66)
  • Vehicle shampoo twice a week for 28 days (n=60)
• The study endpoints includedglobal lesional score, erythema, pruritus, global efficacy, quality of life (SF12 and DLQI questionnaires) and tolerance measured at 0, 7, 14 and 28 days.

  Results

• The mean lesional score highly significantly improved from baseline to each post-baseline visit (p < 0.0001) in all treatment group.
• CPO/ZP shampoo and ketoconazole foaming gel demonstrated same reducing effect on the lesional score without any significant difference between the two groups at each visit.

Table 1 : Lesional score evolution from D0 to D28 by group of treatment

	Lesional score	CPO/ZP shampoo group N=63	Ketoconazole gel group N=66	Vehicle shampoo group N=60	P value†
D0	Mean ± SE	46.46	46.11	45.37	0.831
	Median (range)	42	42	42
D7	Mean ± SE	20.37	19.00	24.05	0.071
	Median (range)	18	16.00	23.00
	Variation from baseline	– 26.10	– 27.11	– 21.32
	P value*	< 0.0001	< 0.0001	< 0.0001
D14	Mean ± SE	11.32a	10.20b	22.98c	< 0.0001
	Median	6	6.00	24.50
	Variation from baseline	– 35.14a	– 35.91b	– 22.38c
	P value§	< 0.0001	< 0.0001	< 0.0001
D28	Mean ± SE	30.00	29.12	27.60	0.857
	Median	32	27.50	25.00
	Variation from baseline	– 16.46	– 16.98	– 17.77
	P value*	< 0.0001	< 0.0001	< 0.0001

* Evolution from baseline: Wilcoxon and Student paired test. § Evolution from baseline: Student paired test. † Between-group comparison (a and b versus c, a versus b): variance analysis and Student-Newman-Keuls. SE: standard error. - a versus b, p=NS. - a versus c and b versus c, p<0.05. 

Improvement in clinical symptoms

• Significant improvement in clinical symptoms (erythema and pruritus) was observed with all treatments.

  Erythema

• There was no significant difference in effectiveness between CPO/ZP and ketoconazole at day 7 and day 14.
• At day 28, CPO/ZP shampoo had a slight advantage.
• The vehicle shampoo was significantly less effective than both treatments at day 7 and day 14, with no significant difference at day 28.

Pruritus

• At day 7, CPO/ZP shampoo was more effective than ketoconazole foaming gel and vehicle shampoo in reducing pruritus (p = 0.032 and p < 0.001 respectively), while ketoconazole gel and vehicle shampoo had a similar effect (p = 0.133).
• At day 14, both CPO/ZP shampoo and ketoconazole foaming gel were equally effective (p = 0.365), but more effective than the vehicle shampoo (p = 0.002 and p = 0.0001 respectively).
• At day 28, all treatments had the same effect. Throughout the study, pruritus significantly improved from day 7 for all treatments (p < 0.0001), with a slight decrease at day 28.

Global Efficacy

• The 2 antifungal treatments (CPO/ZP shampoo and the ketoconazole foaming gel)had the similar efficacy according to the investigator and were highly significantly more efficient than the vehicle shampoo (p < 0.0001) in reducing or curing seborrheic dermatitis and its symptoms
• In subject assessment, more patients treated by the CPO/ZP and ketoconazole shampoos considered they were ’satisfied’ and ’very satisfied’, compared of the patients treated with the vehicle shampoo

Figure 1 : Global efficacy of the treatments assessed at D28 by the investigator and the patient.

Safety/Tolerability

• CPO/ZP, ketoconazole, and vehicle shampoos were equally well tolerated by 96.7%, 98.4% and 94.9% patients respectively.
• 12 patients experienced mild to moderate adverse events.
• Common adverse events included scalp and face erythema, burning sensation, which resolved spontaneously in half of cases.

Quality of life

• SF-12 score analysis showed no significant improvement in mental or physical components for any of the three shampoos (CPO/ZP, ketoconazole, vehicle) over 28 days.
• In the DLQI scores analysis, after 28 days, both the CPO/ZP shampoo and ketoconazole gel significantly improved DLQI scores more than the vehicle shampoo, with mean increases of 4.68 and 3.72 points respectively compared to 2.07 points (p < 0.05 in both cases).
• Only the CPO/ZP shampoo showed a significant improvement from baseline for all 6 dimensions of the DLQI, while the ketoconazole gel and vehicle shampoo did not significantly improve certain dimensions such as "work," "leisure," and "treatment."

Conclusion

• The study demonstrated that CPO/ZP shampoo was rapid and effective as ketoconazole gel in SD treatment
• CPO/ZP shampoo significantly reduced the extent and severity of scaling measured by the lesional score, as well as erythema and pruritus related to the disease

Reference

Eur J Dermatol 2006; 16 (5): 558-64