Clinical Study Exorex vs. Dovonex

Coal tar has been used over a century for psoriasis vulgaris as a stand‐alone treatment or in combination with other therapies, in particular ultraviolet (UV) B (known as the Goeckerman regimen).¹, ² Although of proven efficacy, the use of coal tar formulations has been limited by their unpleasant odour and the staining of skin and clothes. Consequently, with the development of new topical psoriasis medications such as vitamin D analogues³, ⁴ and the synthetic retinoid tazarotene,⁵ coal tar has lost much of its former importance as an antipsoriatic agent.

Exorex lotion is a novel patented fatty acid‐based 1% coal tar preparation. Compared with other coal tar preparations, this new product has markedly improved cosmetic properties, e.g. substantially less odour and staining, and ease of application. However, studies examining the efficacy of this 1% coal tar preparation are few. In a small trial comprising 15 evaluable patients with plaque type psoriasis the 1% coal tar preparation was found to be as effective as calcipotriol.⁶ The present investigator‐blind, randomized, controlled intrapatient study was performed to gather more data on the relative efficacy, safety and patients’ acceptance of the novel 1% coal tar preparation in comparison with calcipotriol cream.

Patients and methods

Patients

Forty consecutive out‐patients with largely symmetrical chronic plaque type psoriasis were included in this trial. All patients received full information on the purpose and design of the study and had not received any systemic or topical psoriasis treatment within 4 weeks before entering the study.

Treatment

In each patient two comparable target plaques of 3–10 cm in diameter were randomly allocated to twice daily treatment with 1% coal tar preparation (Exorex^®, Meyer Zall Laboratories, George, South Africa) or calcipotriol cream (Psorcutan^®, LEO Pharmaceutical Products, Ballerup, Denmark). Patients were randomized in blocks according to a computer‐generated randomization list (Rancode Plus, Version 3.1). The target plaques were always of identical clinical severity and located on sites with the same likelihood of responding to topical treatment (e.g. left vs. right arm, upper vs. lower abdomen, outer vs. inner aspect of the leg). Treatment was performed until almost complete (slight or moderate residual erythema without infiltration and scaling) or complete clearing or over a maximum period of 8 weeks. Patients were asked to use the study preparations as recommended by the manufacturer and to wash their hands after applying the first preparation to prevent its transfer to the other target plaque.

All but two of the patients had generalized psoriasis and were therefore placed on narrowband UVB phototherapy three times weekly for the remainder of their body. Concomitant phototherapy was chosen because it effectively clears widespread moderate‐to‐severe psoriasis yet does not exert a systemic therapeutic effect. To exclude a local effect the target plaques were always shielded from UV exposure by rubber templates that completely blocked the transmission of narrowband UVB. No other treatments were allowed with the exception of emollients.

Assessment of clinical response, tolerability and cosmetic acceptability of treatment

The psoriasis severity index (PSI) of the two target lesions was evaluated by a blinded investigator at baseline, at biweekly intervals during the study period, and at 1, 3, 6, 12 and 18 months after discontinuation of treatment. The PSI score corresponds to the sum of the grading for erythema, infiltration and scaling on a five‐point scale (0, absent; 1, slight; 2, moderate; 3, severe; 4, very severe) with a maximum score of 12. There was always an interval of at least 2 h between application of the study preparations and the clinical assessment by the blinded observer.

Throughout the whole treatment period any adverse event related to the study preparations was registered. In addition, at each clinical visit the cosmetic acceptability (odour, staining) of the two treatments was rated by the patients.

Statistical analysis

The evaluation of efficacy of treatments was based on reduction in PSI scores (difference between baseline and end of treatment). Missing data were replaced using the last observation carried forward method. Within‐subject differences in PSI reduction were compared between 1% coal tar preparation and calcipotriol using the Wilcoxon matched pairs signed rank test. In addition, the 95% confidence interval (CI) for the mean intraindividual differences was calculated.

For comparison of additional efficacy parameters (number of weeks until clearance; time interval until relapse), the Wilcoxon matched pairs signed rank test was used.

Results are reported as mean ± SD. All P‐values reported are two‐sided. P < 0·05 was considered significant.

Results

Of 40 patients 38 completed the study. One patient was excluded from evaluation because of intercurrent illness and irregular application of the study preparations; another patient defaulted for reasons unrelated to treatment. The mean age of the 38 evaluable patients was 43·7 ± 13·9 years; the mean duration of psoriasis was 15·7 ± 10·5 years. Twenty‐seven patients were male and 11 female. The two target lesions were localized on the legs in 23 patients, on the trunk in eight patients and on the arms in seven patients, respectively. The mean treatment period was 6·1 ± 1·67 weeks for 1% coal tar preparation and 6·3 ± 1·87 for calcipotriol. In general, it was not possible to determine by smell or colour which plaque had received which treatment except in four patients in whom the coal tar‐treated plaque was discernible by a light yellow stain.

At termination of the study the mean baseline PSI score of 9·2 ± 1·5 was reduced to 3·0 ± 2·9 by 1% coal tar preparation and to 2·8 ± 2·7 by calcipotriol (Fig. 1). The mean reduction in PSI value between the baseline and final assessment was 6·2 ± 3·1 for 1% coal tar preparation and 6·3 ± 2·8 for calcipotriol (P = 0·77). The mean individual difference in reduction of PSI score between 1% coal tar preparation and calcipotriol was 0·1 score points (95% CI: − 0·84 to 0·63 or −13·4% to 10·0%). Thus, with a probability of 95% the reduction of the PSI score induced by 1% coal tar preparation was between 13·4% inferior and 10·0% superior to calcipotriol.

Figure 1

Reduction of psoriasis severity index (PSI) score by 1% coal tar preparation and calcipotriol cream. Results (last observation carried forward) are given as mean ± SD.

Both preparations led to (near) complete resolution in 22 of 38 target plaques. The mean number of weeks until clearance was 5·5 ± 1·7 for 1% coal tar preparation and 5·4 ± 2·0 for calcipotriol (P = 0·76). A substantial difference in clinical efficacy between the two preparations was observed in only five patients; of these two responded better to 1% coal tar preparation and three to calcipotriol.

Nineteen patients were available for follow‐up. In one patient the target plaques were still clear at 18 months after treatment. In the remaining 18 patients the mean remission period was 4·1 ± 2·9 months for 1% coal tar preparation and 4·4 ± 2·8 months for calcipotriol (P = 0·32). In all but one patient the remission period was the same for both treatments.

Side‐effects were limited to itching and were caused by 1% coal tar preparation in four and calcipotriol in one patient, respectively. Cosmetic acceptability of the two preparations was in favour of calcipotriol. Two patients rated the smell of the novel 1% coal tar preparation as unpleasant and two patients each reported slight or marked staining of their clothes. Only one patient complained about the smell of the calcipotriol cream.

Discussion

Our data corroborate a previous pilot study⁶ that showed a novel 1% coal tar preparation to be about as effective as calcipotriol in treating plaque type psoriasis. In both that and our trial, the difference in clinical efficacy between the two preparations was not significant. In the former study, the scores for erythema, scaling and plaque thickness were decreased by 41%, 56% and 31% by 1% coal tar preparation and by 42%, 63% and 47% by calcipotriol, respectively, after a mean treatment period of 64 days. In our trial, the reduction of the summed score for erythema, scaling and plaque thickness was 67·4% for 1% coal tar preparation and 69·6% for calcipotriol after a mean treatment period of 6·1 and 6·3 weeks, respectively.

It is of note that despite the shorter treatment period the response to both medications was better in our trial. The reason for that is unclear as both studies used a virtually identical study design. However, our data are based on more than twice as many patients and thus might give a more accurate estimation of the overall treatment response. In addition, the patients in our study had a higher disease severity score at baseline. The clinical response to calcipotriol observed in our investigation is also in close agreement with a randomized double‐blind, multicentre, right–left comparison of calcipotriol and betamethasone valerate in psoriasis that found a 68·8% reduction of psoriasis area and severity index (PASI) score with calcipotriol after 6 weeks of treatment.⁷

Published data on the novel 1% coal tar preparation are scarce and include only one further controlled study that assessed the clinical efficacy of this preparation with and without its essential fatty acid component (referred to as ‘coal tar control’) in 20 patients with moderate plaque type psoriasis. After 8 weeks of treatment the reduction of the summed target plaque score was 53·9% for novel 1% coal tar preparation and 56·1% for the coal tar control, suggesting that the complex of esterified essential fatty acids is not exerting any clinically important therapeutic effect.⁸

A comparative study of twice daily calcipotriol ointment vs. once daily 15% coal tar solution in aqueous cream in 30 patients with moderate plaque type psoriasis gave significantly better results for calcipotriol at all evaluation points.⁹ After 6 weeks of treatment the reduction of PASI score was 69·8% with calcipotriol as opposed to only 30·9% with coal tar. However, in that study coal tar was applied only once daily; therefore it is not possible to draw meaningful conclusions about the relative therapeutic efficacy of other coal tar preparations in comparison with the novel product.

Recently, a right–left comparison of twice daily calcipotriol ointment and once daily 5% coal tar ointment in conjunction with sun exposure was carried out over 8 weeks in 10 patients with stable plaque psoriasis. It was concluded that both preparations were comparably effective when used simultaneously with sun exposure, although the initial response to calcipotriol was faster.¹⁰

Calcipotriol was slightly better tolerated and had a higher patients’ acceptance than 1% coal tar preparation in our trial. On the other hand, adverse events caused by the new 1% coal tar preparation were in general mild and the cosmetic properties were found to be largely improved in comparison with older coal tar preparations. In addition, while providing a similar degree of clinical improvement and length of remission, the new coal tar product is several times less expensive than calcipotriol. Its use would therefore be supported by cost–benefit considerations. Taken together, the novel 1% coal tar preparation appears as a very useful topical treatment for chronic moderate‐to‐severe plaque type psoriasis.

Acknowledgments

This study was supported by a grant from Meyer Zall Laboratories, George, South Africa.

References