The efficacy of a far erythemogenic dose of narrow- band UVB phototherapy in chronic plaque type psoriasis

Transcription

1 1 The efficacy of a far erythemogenic dose of narrow- band UVB phototherapy in chronic plaque type psoriasis ผ ว จ ย Rutsanee Akaraphanth MD, Yotsinee Kittipavara MD, Nataya Voravutinon MD, Usa Wachiratarapadorn MD, Pimonpun Gritiyarangsan, MD. Ph. D. Institute of Dermatology, Bangkok, Thailand Address: 420/7 Rajvithi road, Phayathai, Bangkok 10400, Thailand Tel. : Fax : akaraphanth@ hotmail.com Abstract: To study the effect of far erythemogenic dose of NB-UVB (starting dose at 35% MED ) on clinical response by measuring the severity, extent of disease and the changes in quality of life. Fifty patients with chronic plaque type psoriasis were enrolled. Therapy was held for three days a week. The severity of the disease was assessed based on the Psoriasis Area and Severity Index (PASI) score and Dermatology Life Quality Index (DLQI) scores. The percentage improvement of PASI at 30 sessions was 68.99%. The improvement in DLQI scores at 30 sessions was 79.67%. Pearson correlation coefficients showed that PASI scores were not correlated with DLQI scores at the beginning of treatment (p=0.330, r=0.14), but after 30 th session of NB-UVB therapy an improvement in quality of life were correlated (p<0.05, r=0.399). Therefore far erythemogenic doses of NB-UVB is considered to be effective treatment for plaque type psoriasis in.our patients. However, we cannot confirm that it is safer than higher MED starting dose in term of cumulative UV irradiation Key words : Chronic plaque type psoriasis, DLQI score, far erythemogenic dose NB-UVB, PASI Score

2 2 Acknowledgements We thank Dr Kanokvalai Kulthanan for allowing us to use the validated Thai DLQI scores. We are also grateful to all our photobiologic staff for their help in recruiting and taking care of patients for this study. Introduction Narrow-band UVB (NB-UVB) has been proven to be effective treatment for Plaque type psoriasis. 1 Most previous studies used near eythemogenic (70% MED) 2 or sub erythemogenic doses of NB-UVB (50% MED). 3-4 However, the long term risk of prematurephotoaging or photocarcinogenesis with NB-UVB is remains undetermined in clinical practice. The objective of this study was to investigate the effect of far erythemogenic doses of NB-UVB ( 35% MED ) on clinical response by measuring the severity and extent of disease, using the Psoriasis Area and Severity Index (PASI) score Psoriasis causes patient morbidity and can have serious effects on a patient s quality of life (QoL) due to discomfort, itchiness, social stigma and profound psychological disturbance. 5 Measures that describe a patient s experience of medical care, such as the QoL measure, are useful and important to determine the traditional physical, psychological and biological consequences of the disease and treatment. Broader dermatologic questionnaires, such as the Dermatologic Life Quality Index (DLQI) were developed in Wales by Finlay and Khan to measure the effect of skin disorders on the quality of patients lives. 6 This DLQI is a simple, validated 10-item questionnaire design to measure and compare disabilities related to different skin conditions. We studied the change in QoL of the patients after treatment and also study the relationships between changes in the DLQI score and PASI after NB-UVB treatment. Material and Methods A prospective study was conducted at The Phototherapy clinic, Institute of Dermatology, Bangkok, Thailand. Fifty patients with chronic plaque type psoriasis aged 18 years or older with disease involvement of more than 20% of the body surface area and disease inadequately controlled with topical therapies were enrolled in the study. Exclusion criteria included pregnancy or lactation, a history of cutaneous malignancy, systemic treatment such as methotrexate or retinoids within one month prior to the study. Patients were excluded if they had a history of PUVA or NB-UVB within 3 months prior to the study. The study protocol was approved by the Hospital Ethics Committee and each patient provided written informed consent to participate in the study

3 3 Narrow-band UVB source Phototherapy was given in a spectra 311 cabin (Daavlin, Bryan, Ohio 43506, USA) equipped with 24 TL-01/100 W fluorescent lamps (Phillips company, Eeinhoven, The Netherlands) producing a narrow-band peak UVB emission at 311 nm. The irradiance was determined with an international Light (IL) 1400 research radiometer (international Light Inc., Newburyport, MA, USA). Irradiance in the Daavlin cabinet ranged from 2.1 to 2.8 mw/cm 2 during the course of the study. Treatment protocol Before starting treatment, the minimal erythema dose (MED) was determined in each patient. The patients were exposed to TL-01 tubes in doses ranging from 210 to 1500 mj/cm on six test sites on the lower back. The dose was adjusted depending on the patient s skin type. The smallest dose of UVB to result in barely perceptible erythema (MED) was judged at 24 hours after irradiation. Therapy was held three days a week and dose of 35% of the determined MED, with an increase of 20% and then reduction in 10% increments at each visit depending on each individual s erythema response. For barely perceptible erythrema, the previous dose was repeated. Erythema episodes were recorded. Grade 1 (ill-defind), grade 2 (well demarcated, not painful), grade 3 (painful erythema) and grade 4 ( blistering). For well defined erythema, the next one session was postponed, the dose was repeated, and then reduced by a 10% increment. For grade 3 and 4, treatment was postponed and reduced to 30% to 50% of the previous dose. No further incremental increases were applied once a dose of 3.5 mj/cm 2 was achieved. The secondary dose was also given in the patient who got thick and large lesion on extremities. Twenty percent of total body dose was given. The increment regimen was the same as body. The treatment was continued either until clearance was achieved (defined as PASI 75) or until maximum improvement has been obtained. All patients were advised to continue with their topical therapy such as 5% LCD, 5% CCT, salicylic acid, steroid and dithranol on the days that they were not receiving phototherapy. Only liquid paraffin was permitted to be used on the days of treatment. Assessment The severity of the disease was assessed based on the PASI score 7 and Dermatology Life Quality Index (DLQI) score. The PASI has a maximum value of 72 and the DLQI score has a maximum value of 30. The DLQI score contains 10 question measures regarding symptoms, feelings, daily activities, leisure, work/school, relationships and treatment occurring in the last week. The Thai version DLQI which has been validated by Kulthanan et al was applied in our study. 8 A higher the

4 4 score indicates a greater the impact on the patient s quality of life. The second and third sessions of PASI and QoL assessments were made at 12 th and 30 th weeks of treatment. An improvement of 75% from initial PASI score was defined as PASI 75. PASI 50 is an improvement of 50% from the baseline. The cumulative NB-UVB doses for clearance were calculated. Patients who achieved PASI 75 or PASI 50 were followed up for 1 year or until relapse. Relapse was defined as patients who achieved a clinically meaningful response with disappearance of 50 percent of PASI improvement from baseline during the follow up period. 9 Stasistical methods Differences in PASI scores and DLQI scores at baseline, 12 th session and 30 th session were compared using the two dependent sample t-test. The relationship between QoL and clinical outcome parameters were quantified by using Pearson correlation coefficients. Results The subjects were 12 females and 38 males. The average age was 42 years (ranging from 20 to 71 years). The mean age of onset was 33.7 years. The mean duration of disease was 8.2 years. According to the classification by Fitzpatric, 10 two patients have skin type III, forty two have skin type IV and 6 have skin type V ( Table 1). Most of our patients had skin type IV, their MED were around 570 to 800 mj/cm 2. A small number of patients had at MED of 210, 300, 410, 1100 and 1500 mj/cm2. The average dose of MED was 661 mj/cm2. (Figure 1) The mean PASI score at baseline, 12 th and 30 th sessions of treatment were 13.57, 8.98, and 4.49 respectively. The percentage improvement of PASI at 12 sessions was 38% from baseline and approximately 68.99% when NB-UVB treatment was continued through to 30 sessions (Table II ). Paired T-tests showed significant differences in PASI scores at the beginning, 12 th and 30 th sessions of treatment (p<0.001 and p< respectively). The mean DLQI scores at baseline, 12 th and 30 th sessions of treatment were 11.58, 6.08 and The improvement in DLQI score at 12 and 30 sessions were 51.43% and 79.67% respectively (Table II ). Paired T-tests showed a significant difference in DLQI score at baseline, 12 th and 30 th session (p<0.001). At the end of 30 sessions, sixteen patients (32%) reported a DLQI of 0" meaning that they were not at all affected by their psoriasis. Pearson correlation coefficients showed that PASI scores were not correlated with DLQI scores at the beginning of treatment (p=0.330, r=0.14), but after 30 th session of NB-UVB therapy, the quality of life measures correlated with the improvement (p<0.005, r=0.399).

5 5 At the end of the therapy, the mean number of treatment in the whole group study was 35 treatments and the mean number to achieve PASI 75 was 29 treatments The mean cumulative dose of NBUVB was 43,541 mj/cm 2 (ranging from 13,187 to 82,856 mj/cm 2, the mean cumulative secondary dose was 8,612 mj/cm 2. At 12 th session of NB-UVB exposure, two patients (4%) achieved PASI 75 and eighteen patients ( 36%) achieved PASI 50. At 30 sessions, twenty one patients (42%) achieved PASI 75 and eighteen patients (36%) achieved PASI 50. Eleven patients (22%) achieved less than 50 % PASI improvement (Figure 2). Those thirty nine patients who achieved PASI 75 or PASI 50 continued to followed-up in the Dermatology clinic, except for five patients who were not able to follow-up and were not included in the analysis of relapse. Seventeen patients (41%) remained in remission 1 year after cessation of NB-UVB therapy. The remaining patients relapsed, with the average time to relapse being 2.8 months ( ranging from 1 to 8 months). Adverse effects Four patients (8%) had grade 2 reaction and painful erythema ( grade 3 ) occurred in four patients ( 8%). There were no blistering or systemic side effects Discussion NB-UVB was effective in the treatment of patients with chronic plaque type psoriasis who were not responding to topical therapy. We used a regimen of irradiation three times a week which cleared psoriasis faster than twice a week as reported by Cameron et al. 11 Hofer A. et al also reported that far erythemogenic dose ( 35% MED ) of NB-UVB may be equally effective as near erythemogenic dose (70% MED) for plaque type psoriasis but requires slightly more sessions of treatment. George et al. 4 also suggested that far erythemogenic doses of UVB may require smaller cumulative doses. We studied the efficacy of low starting doses of NB-UVB (35% of MED) as it may reduce the cumulative dose and the risk of possible acute and chronic adverse effects of NB- UVB. From our study, the majority of the patients had skin type IV and most of their MED were from 570 to 800 mj/ cm2. This finding should be of value to other phototherapy units treating a similar patient population of skin type IV. The average starting dose in our study was only 231 mj/ cm2. We also used low increments in doses, including 20% to 10% reductions depending on the patient s erythema response. We found that low dose of NB-UVB achieved marked improvement in the clinical severity of psoriasis as documented by a significant decrease in PASI score compare

6 6 between baseline and 30 sessions of treatment. Forty two percent of patients achieved PASI 75 and thirty six percent achieved PASI 50 at the end of treatment. Compared with new biologic treatments such as alefacept, efalizumab or etanercept at 12 weeks, the percentage of patients that achieved PASI 75 were 29% 16, 41% 17 and 49% 18 respectively. Our study produced nearly the same response. The clearance rate of our patients was 68% at 30 sessions. The results here in and the comparison with previous studies on the treatment of chronic plaque type psoriasis with NB-UVB are highly consistent with the clearance rate of a previous study by Yones SS et al. 15 where 70% MED with three treatments a week achieved 65% clearance. The study by Gordon et al 15 also showed 63% improvement. Forty one percent of our patients were still in remission 1 year after the cessation of therapy and the average times to relapse was 2.8 months. Effective treatment of psoriasis with 70% MED of NB-UVB was also described by Green et al. 2 They reported that 38% of their patients had 1 year remission and the average times to relapse was 3 months. Concomitant with the clinical changes, there was marked improvement in the patients quality of life and this was demonstrated in the improvement in the DLQI scores. QoL improved 79% from baseline. At the beginning of the study we did not detect a correlation between clinical severity of the disease and quality of life. However after phototherapy, quality of life correlated with the extent of psoriasis improvement, suggesting that with the treatment we provided, the quality of life was more related to recent changes in psoriasis severity than to the severity of psoriasis itself. On completion of the study the mean cumulative dose was 43,541 mj/cm. 2 This cumulative dose is higher than previous study done in Caucasian population. When compare with the study in Asian population done by Leenuthapong Vet al 19. He studied the effect of 50% MED starting dose compare between two times and four times a week of NB-UVB for plaque type psoriasis. There is equivalence in term of clearance (60%), number of treatment (32 treatments) and the percentage of adverse effect (12%-13%). However the mean cumulative dose of our study was not lesser than 50% MED starting dose (43,541 mj/cm 2 compared with 40,100 mj/cm 2 ). The regimen of increment of the two studies was different. Leenuthapong V et al gave increment every three treatment by 40%, 30%, 20%, 10%, 5 % and then no increment. We give 35% MED then increase of 20% and reduction in 10% increments until erythema appeared. Most of our patient had thick and large plaque especially on their extremities therefore most of them receive

7 7 secondary dose. These may be another reason why our patients had higher cumulative dose. Conclusion Far erythemogenic doses of NB-UVB is considered to be as effective as near erythemogenic doses (75% MED) or sub erythemogenic doses ( 50%MED ) for plaque type psoriasis. It can decrease the disease severity and improve QoL in a vast majority of patients. However from this study we could not confirm that it will be safer than higher MED starting dose in term of cumulative UV irradiation. Figure 1. The MED of the patient with skin type III, VI, and V Minimal Erythema Dose (MED) III IV V Figure 2. At 12 th session, two patients (4%) achieved PASI 75. Eighteen patients (36%) achieved PASI 50. At 30 sessions, twenty one patients (42%) achieved PASI 75 and eighteen patients (36%) achieved PASI 50. % of patients 70% 60% 50% 40% 30% 20% 10% 0% 60% 36% 36% 42% 4% 22% 12 sessions 30 sessions Time PASI <50 PASI 50 PASI 75

8 8 Table I. Demographic data of the patients Total number of patients 50 Male 38 Female 12 Average age 42 years ( years ) Average age at onset 33.7 years ( years ) Mean duration of psoriasis 8.2 years ( 1 26 years ) Skin photo type Type III 2 Type IV 42 Type V 6 Average MED 661 mj/cm2 (range mj/cm2) Table II. Mean PASI scores, DLQI scores, and percentage of improvement in PASI scores, DLQI scores at the baseline, 12th and 30th sessions of treatment. PASI Score % Improvement Baseline 13.57(±4.81) 12 th sessions 8.98(±5.68) 38 % 30 th sessions 4.149(±4.08) 68.99% DLQI Baseline 11.58(±4.81) 12 th sessions 6.08(±4.15) % 30 th sessions 3.1(±3.91) 79.67%

9 9 References: 1. Bandow GD, Koo JY. Narrow-band ultraviolet B radiation: a review of the current literature. Int J Dermatol 2004; 43: Green C, Ferguson J, Lakshmipathi T, Johnson BE. 311 nm UVB phototherapy - an effective treatment for psoriasis. Br J Dermatol 1988; 119: Walters IB, Burack LH, Coven TR, Gilleaudeau P, Krueqer JG. Suberythemogenic narrow - band UVB is markedly more effective than conventional UVB in treatment of psoriasis vulgaris. J Am Acad Dermatol 1999; 40: George SA, Collins P, Wainwright NJ, Ferguson J. Narrow band UVB Psoriasis phototherapy; normal vs low (half) dose irradiation regimens. Br J Dermatol 1993; 129 ( Suppl 42): Finlay AY, Khan GK. Dermatology Life Quality Index (DLQI) - a simple practical measure for routine clinical use. Clin Exp Dermatol 1994; 19: Finlay AY, Khan GK, Luscombe DK, Salek MS. Validation of Sickness Impact Profile and Psoriasis Disability Index in Psoriasis. Br J Dermatol 1990; 123: Fredriksson T, Pettersson U. Severe psoriasis - oral therapy with a new retinoid. Dermatologica 1978; Kulthanan K, Jiamton S, Wanitphakdeedecha R, Chantharujikaphong S. The validity and reliability of the Dermatologic Life Quality Index (DLQI) in Thais. Thai J Dermatol 2004; 20: Carey W, Glazer S, Gottlieb AB, et al. Relapse, rebound, and psoriasis adverse events: an advisory group report. J Am Acad Dermatol 2006; 54 (4 Suppl1): S Fitzpatrick TB. The validity and practicality of sun - reactive skin types I through VI. Arch Dermatol 1988; 124: Cameron H, Dawe RS, Yule S, Murphy J, Ibbotson SH, Ferguson J. A randomized, observer - blinded trial of twice vs. three times weekly narrowband ultraviolet B phototherapy for chronic plaque psoriasis. Br J Dermato 2002; 147: Hofer A, Fink-Puches R, Kerl H, Wolf P. Comparison of phototherapy with near vs. far erythemogenic doses of narrow - band ultraviolet B in patients with psoriasis. Br J Dermatol 1998; 138: Yones SS, Palmer RA, Garibaldinos TT, Hawk JL. Randomized double - blind trial of the treatment of chronic plaque psoriasis: efficacy of psoralen - UVA therapy vs narrowband UV-B therapy. Arch Dermatol 2006; 142: Markham T, Rogers S, Collins P. Narrowband UV-B (TL-01) phototherapy vs

10 10 oral 8-methoxypsoralen psoralen UVA for the treatment of chronic plaque psoriasis. Arch Dermatol 2003; 139: Gordon PM, Diffey BL, Matthews JN, Farr PM. A randomized comparison of narrow-band TL-01 phototherapy and PUVA photochemotherapy for psoriasis. J Am Acad Dermatol. 1999; 41: Papp KA. The long term efficacy and safety of new biological therapies for psoriasis. Arch Dermatol Res 2006; 298: Menter A, Leonardi CL, Sterry W, Bos JD, et al. Long - term management of plaque psoriasis with continuous efalizumab therapy. J Am Acad Dermatol 2006; 54 (4 Suppl 1) : S Boehncke WH, Brasie RA, Barker J, et al. Recommendations for the use of etanercept in psoriasis: a European dermatology expert group consensus. J Eur Acad Dermatol Venereol 2006; 20: Leenutaphong V, Nimkulrat P, Sudtim S. Comparison of phototherapy two t times and four times a week with low dose of narrow - band ultraviolet B in Asian patients with psoriasis. Photodermatol photoimmunol photomed 2000; 16: