Tibicorten and Betamethasone Valerate: A Double-Blind Comparative Study

Transcription

1 J Int Med Res (1911) 5,338 Tibicorten and Betamethasone Valerate: A Double-Blind Comparative Study D J Tazelaar, MD, Department of Dermatology, Ziekenhuis 'De Tjongerschans', Heerenveen, The Netherlands Tibicorten, a new ßuorine-substituted corticosteroid for topical application, was compared with betamethasone valerate in a double-blind investigation with left-right examinations. There appeared to be no significant difference between the resuhs obtained with each substance in the treatment of patients with acute or chronic eczema or with psoriasis. Introduction Triamcinolone acetonide β -benzoylaminoisobutyrate (), an isobutyric acid ester of triamcinolone acetonide (TCA) developed by Diamanti and Bianchi in 1971, appears to possess a higher local anti-inflammatory activity than triamcinolone acetonide, as has been determined by pharmacological trials on animals (Troilo Ordonez 1971, Troilo Ordonez 1974). Furthermore, less general systemic effects have been observed. It was consequently possible to reduce the concentration of 01%, empirically recognized as optimal for triamcinolone acetonide, to 0-075% for. The first controlled clinical investigations (Bertamino 1974, La Rosa, Albanese & Sposato 1974, Simoni 1974) showed that is a very useful corticosteroid for the local treatment of cases of dermatoses amenable to corticosteroid therapy. Given below are the results of a double-blind investigation, according to the left-right method, in the course of which the activity of (0-075%) was compared with that of betamethasone-17-valerate (0-1%) in patients with acute and chronic eczema or with psoriasis. Materials and Methods The investigation was divided into two parts (Table 1). In the first part, an ointment of both corticosteroids was applied to 25 out-patients with, in most instances, constitutional eczema (12) or psoriasis (13). It concerned 14 men and 11 women with an average age of 44 for the former and 53 for the latter. Nineteen of the patients had previously received topical treatment with a corticosteroid or a tar preparation. The ointment was applied once a day in 6 cases, twice daily in 17 cases

2 DJTazelaar 339 Fig 1 Triamcinolone acetonide benzoyl-'^-amino-isobutyrate and three times a day in 2 cases. An occlusive dressing was used in 19 patients. In the second part, the activity of a cream was compared with that of a betamethasone-17-valerate cream in 12 patients, also ambulatory, (4 men and 8 women) presenting acute exacerbation of constitutional (1) or contact eczema (11). The creams were applied twice daily in 5 cases, three times daily in 6 cases and four times a day in 1 case. Naturally, no occlusive dressing was used here. All the patients presented bilateral lesions, which were comparable in character and intensity. At the start of the investigation, each patient received two tubes bearing a number and the indication 'left' or 'right', according to the side of the body to which the contents of that particular tube was to be applied. Assigned by pairs, one of the tubes contained cream or ointment and the other contained betamethasone valerate (B) cream or ointment. The cream and ointment excipients were identical for both corticosteroids, so that neither preparation could be distinguished by colour, odour or consistency. Neither the physician nor the patients were aware of the contents of the tubes. The use of any other topical or systemic preparations such as corticosteroids, antihistaminics or antipruritics was forbidden. Before the test and at each control-period (after 2, 7 and 14 days), the state of the skinlesions was evaluated in accordance with five objective criteria, namely erythema, oedema, papulae, vesicles and excoriation and one subjective criterion, namely itching. On each occasion and for each criterion, the left and right sides were judged separately and intensity scores were given as follows: severe + + moderate -I- slight - none At the same time, it was also noted if any sideefiects had occurred or not. Finally, at the last control-period i.e. after 14 days, an overall evaluation was made of the

3 340 The Journal of International Medical Research Table 1 Detallt ofpatienti Pari 1: Ointment Part 2: Cream Number Sex Men Women Age (mean) (19-70) (21-83) Men Women (12-71) (12-80) Diagnosis Eczema Psoriasis Acute eczema Previously treated Table 2 Evolution of symptoms (mean value ± s.d.) Before After 2 days After? days After 14 days Psoriasis (n = 13) ± ± ^ ± 1-73 Eczema (n = 12) ± ± ± ± ± 2-33 Total (η = 25) 7-52 ± ± ± ± ± 1-95 Table 3 Overall evaluation Psoriasis Eczema Total Cure(C) Improvement (I) Failure (F) η =

4 D J Tazelaar 341 Table 4 Comparative results: Tibicorten and betamethasone valerate C I F C I F C I F C C C I I I F F F Tables Evolution of symptoms (mean values ± s.d.) Before After2davs Afler7 davs After 14 days (n = 12) (n = 12) (n ) (n = ll) 9 00 t ± * ± 1-06 Tableó Overall evaluation Cure 6 1 Improvement 6 5 Failure 0 0 Table 7 Comparison between Tibicorten and betamethasone valerate in cream-form C I F C I F 0 0 0

5 342 The Journal of International Medical Research results obtained for the left and right sides separately. These results were expressed as follows: failure (F), improvement (I) or cure (C). Statistical analysis of results was carried out in accordance with the McNemar method. A 'p' value inferior to 0-05 showed a statistically significant difference between the results obtained with each corticosteroid. Resuhs Part I: Ointment-form Table 2 shows the mean values (± s.d.) of the sum of all symptoms before the start of the investigation and also 2, 7 and 14 days after treatment for the 12 eczema cases and the 13 patients with psoriasis considered as separate groups and then for all the patients taken as a whole. There was no significant difference between the results obtained with the two preparations, whether in the two groups of skin-affections taken separately or in the total number of patients taken as a whole. In all (Table 3), 17 cures and 27 improvements were noted amongst the individual skin-lesions (left or right). In 6 cases treatment had still failed after 14 days. A certain degree of superiority of betamethasone valerate over Tibicorten can be seen in patients with psoriasis. The overall results obtained with both preparations in the treatment of eczema appear to be equivalent. Analysis of the relationship between left and right showed (Table 4) that in 16 out of 25 cases there existed no difference between left and right; in 2 cases the -treated side was better and in 7 cases the B-treated side. This nonsignificant diflterence (ρ = 18) in favour of betamethasone valerate, was mainly caused by the better results which were observed with this substance in psoriasis: 7 times equal and 1 result and 5 results better (p = 22). Among the eczema patients, on the other hand, results were identical in 9 out of 12 cases, in 1 case was > and in 2 cases >. Part 2: Cream-form Table 5 shows the evolution of the mean values of all symptoms taken together (± s.d.) after 2, 7 and 14 days of treatment of 12 patients suffering from an acute exacerbation of eczema with a Tibicorten cream (0-075%) and a betamethasone-valerate cream (0-1%). As in the first part of this investigation, the results of Tibicorten and betamethasone valerate were identical. After 2 and 7 days of treatment there was a slight, but not significant, advantage in favour of Tibicorten. In no case was a course of treatment considered as a failure (Table 6). Of the 13 'cured' lesions, 6 had been treated with and 7 with B. At the end of the investigation, there was a clear improvement in 11 cases: 6 with and 5 with B. Once again, this difference is not significant. When compared with each other (Table 7), both preparations gave identical results in 9 patients. In 1 case, the -treated side was cured and the B-side improved. Finally, the results on the betamethasoneside appeared to be better in 2 cases than on the TBl-side. This difference is not significant. Tolerance Tibicorten and betamethasone valerate, both cream and ointment, were perfectly tolerated by all patients. At no time were there any signs of irritation, burning or atrophy. Discussion From the above results it appears that the isobutyric acid ester of triamcinolone acetonide (TB) exerts, when applied topically to lesions which are amenable to corticosteroids, an effect which is equivalent to that of the already wellknown betamethasone valerate. While the results obtained in the treatment of both acute and chronic eczema seem to be the same for both substances, with commencing its action slightly more rapidly, the latter was a little less effective in the treatment of psoriasis than betamethasone valerate. It should be added, however, that betamethasone valerate was used in a higher concentration (0-1%) than (0-075%). Acknowledgements The (Tibicorten) used in this study was supplied by Labaz V, Maassluis.

6 D J Tazelaar ü - U U O ^ U O U U «U - ^ U L i. U Q 5 ^ u. uuuu ^ u-p- u ^ u,cj υ NJOO ( N -RTTTO'-C O <~s Θ Γ ^ ) «Η Θ ' ^ 0 5 * R-J «O RSI RSIR^rsjrNir-jTjiv-IR-JR^R*^ FN^C O <^θθγν)ΐλί, «ri C> R^jΓΝΐ R--, IT) Tí IR-) o^υ^w->γ^ TOR*-ITJ ΤRΤJ R*-, VOR-RJSO'ÍF 03 to" v2 OOCCX'«RIC»ÜOONVOOOCO^IOC>\CC>OR--'«5-»R)> ;»O^C O O R - «c ra Ε ^ α. α. ο π öl UÜ υ δ ε ω 1^ ^ ο. υ χ (U χ - ε ϋ χ ω χ ««-5;?i «-5; -53 «*ί C I -c α I -ΰ -c ^ -c -c -c π I «ζ Q. κ I. t.^ U. u..it u. J - Χ.ω.Í:.1. «i u. u.. 8 >< a. a. <

7 344 The Journal of International Medical Research 05 υ - UU UUU <N rg ó O O O r<i rg fñ I O O 6 O so «A O O SO ν-ΐ IT) ó ^O rsl STj V/") STj»/Ί 3 O I 5' 03 Κ OSR-OO OO Γ-Γ- OO ' Ο Γ OO R-R- 00 ' ce w ra ε ε ε υ ω -υ " Ν Ν «CO ε ε Ο ο ο υ υ υ α. υ υ Ε I Ε <υ u υ Μ Ν Ν ο υ υ υ ο Ο ο Ο υ υ υ ea Co ε ε Ν Ν C C ο ο υ U Ια t~-\ t*^ r*-, 'rf r^i i '..I- '.i. ^. X ^ O X -T

8 D J Tazelaar 345 REFERENCES Bertamino R (1974) Un nuovo corticosteroide per uso tópico. Sua valuatazione clinica in condizioni di doppia cecita. La Riforma Medica 88, 1217 Diamanti Ε & Eletti Bianchi G (1971) New esters of triamcinolone acetonide for topical antiphlogistic use.arzniemiriel-forschungh, 251 La Rosa P, Albanese A & Sposato Ν (1974) Studio clínico controllato su un nuovo corticosteroide tópico: il benzoyl- I -amino-isobutirrato di triamcinolone acetonide. Rassegna di Dermalologia e di Sifüografia 26 Simoni R (1974) Syudio in doppia cieco di un nuovo fármaco corticosteroide per uso tópico:. Rassegna di Dermalologia e di Sifilografia 26, 1 Troilo Ordonez Ε (1971) Pharmacological properties of a new corticosteroid derivative: benzoyl- Ii -amino-isobutyrate of triamcinolone acetonide. Arzniemillel-Forschung 21, 248 Troilo Ordonez Ε (1974) Pharmacologic and toxicologic properties of a new topically active inflammatory steroid, Arzniemillel- Forschung 24, 2015