Reduction In Body Surface Area Research Articles

Safety and efficacy of dupilumab in adult atopic dermatitis in Singapore.

Dupilumab, a biologic approved for treatment of moderate-to-severe atopic dermatitis (AD), has been reported to be largely effective with minimal adverse effects. However, being a targeted therapy, its effectiveness and side effects are expected to be varied in a heterogeneous ethnic population. Currently, the majority of studies on dupilumab are based on Western populations. A retrospective cohort of 51 patients with moderate-to-severe AD treated with dupilumab at a tertiary skin institute from January 2018 to February 2020 was included. Outcome measures such as Scoring Atopic Dermatitis (SCORAD), Eczema Area and Severity Index (EASI) and Dermatology Quality of Life Index (DLQI) were analysed at baseline and after 16 weeks of treatment. Laboratory tests at the respective time points were also measured. Patients treated with dupilumab showed consistent reduction in body surface area (BSA) involved, SCORAD, EASI and DLQI scores. Concurrently, serum immunoglobulin E (IgE) and absolute eosinophil count showed a downward trend at 4 months of treatment. There was a transient increase in mean serum IgE at 1 month of dupilumab treatment. Also, 42.0% and 35.3% of patients developed eye symptoms, and head and neck dermatitis, respectively, but there were no major adverse events reported. Childhood-onset AD was more likely to have improved BSA scores compared to adult-onset AD. Our study confirms the efficacy of dupilumab with real-world data in an adult Asian population. Higher proportions of eye symptoms, and head and neck dermatitis were observed in our cohort compared to other Asian clinical cohort studies. Further studies are needed to evaluate these differences.

CO45 Durability of Efficacy and Safety of Roflumilast Cream 0.3% in Adults with Chronic Plaque Psoriasis from a 52-Week, Phase 2 Open-Label Safety Trial

Roflumilast cream is a potent phosphodiesterase 4 inhibitor recently approved in the United States for treatment of plaque psoriasis. An open-label trial was conducted to evaluate long-term safety (52 weeks) of once-daily roflumilast cream (NCT03764475). Durability of response was measured using Investigator Global Assessment (IGA) score of Clear or Almost Clear, percentage improvement in Psoriasis Area Severity Index (PASI) score, and reduction in body surface area (BSA) affected.

Durability of Efficacy and Safety of Roflumilast Cream 0.3% in Adults With Chronic Plaque Psoriasis From a 52-Week, Phase 2 Open-Label Safety Trial

Background: Roflumilast cream is a potent phosphodiesterase 4 inhibitor recently approved in the United States for treatment of plaque psoriasis with no limitations on duration of use. An open-label trial was conducted to evaluate long-term safety (52 weeks) of once-daily roflumilast cream (NCT03764475). This abstract presents data on durability of response as measured by the percentage of patients with an Investigator Global Assessment (IGA) score of Clear or Almost Clear, percentage improvement in Psoriasis Area Severity Index (PASI) score, and reduction in body surface area (BSA) affected. Methods: Patients who completed a parent, phase 2b, 12-week randomized controlled trial could continue on open-label roflumilast cream 0.3% (Cohort-1, n=230), and patients naïve to roflumilast were also enrolled (Cohort-2, n=102). All psoriasis lesions (except scalp) were treated, including face and intertriginous areas for up to 52 weeks. If affected, palms and soles were treated, but not evaluated towards any efficacy assessments. Median duration of response was determined using the Kaplan-Meier method. Results: With cumulative treatment up to 64 weeks in Cohort-1 and 52 weeks in Cohort-2, long-term safety and tolerability were consistent with the 12-week, phase 2b study. Overall, 73.5% of patients completed the study; 3.9% discontinued due to adverse events (AE) and 0.9% discontinued due to lack of efficacy. Treatment-related AEs were reported in 2.7% patients; none were deemed serious. Investigator tolerability assessments at each visit demonstrated 99% of patients rated “no evidence of irritation.” At Week 52, IGA Success (demonstrating Clear/Almost Clear plus 2-grade improvement from baseline) was achieved by 34.8% of patients in Cohort-1 and 39.5% in Cohort-2. Of patients in Cohort-2, 40% of patients achieved IGA success at week 12. IGA Clear/Almost Clear was achieved by 46.8% of patients across both cohorts at week 12 and consistent through week 52 (44.8%). Similarly, a 60.5% mean PASI improvement and 60.1% mean BSA improvement from baseline were observed at week 12 and consistent through week 52 (59.4% and 63.3%, respectively). Of the 185 patients who achieved IGA Clear/Almost Clear during the open-label trial, the median durability of IGA of Clear/Almost Clear was 10 months (40.1 weeks). Among patients who achieved an IGA of Clear or Almost Clear, 50% maintained Clear or Almost Clear status for at least 10 months. Conclusions: In this long-term safety study, roflumilast cream was well tolerated with a safety profile consistent with the parent Ph2b trial, and effectively maintained clear/almost clear skin with no tachyphylaxis observed. Sponsored by Arcutis Biotherapeutics, Inc.

31069 Bimekizumab versus secukinumab in plaque psoriasis: Reduction in body surface area affected by psoriasis translates into benefits in patient-perceived itching, skin pain, and scaling and health-related quality of life in the BE RADIANT phase 3b trial

Introduction: We examined how achievement of BSA affected by psoriasis thresholds translated into benefits in patient-perceived symptoms and health-related quality of life (HRQoL) in patients with moderate to severe plaque psoriasis receiving bimekizumab (BKZ) vs secukinumab (SEC).

Response to Extracorporeal Photopheresis in Patients with Cutaneous T-Cell Lymphoma: A Retrospective Medical Chart Review

INTRODUCTIONExtracorporeal photopheresis (ECP) is an immunomodulatory therapy that has been used in the treatment of cutaneous T-cell lymphoma (CTCL) for over 30 years. Clinical trials of newer agents for the treatment of CTCL have shown response rates of approximately 30% in heterogeneous patient populations. The objective of this study was to assess the effectiveness of ECP in the treatment of CTCL patients in real-world clinical practice.METHODSThis is an interim analysis of a retrospective medical chart review study conducted at clinical sites in the United States, in which treating physicians were responsible for patient selection and data collection via structured case report forms. Patients with a confirmed diagnosis of CTCL who initiated ECP between January 1, 2017 and February 28, 2019 were included in the study. In addition, patients must have initiated ECP at age ≥18 years with no ECP treatment received within the year prior to data collection, have received at least 3 months of ECP treatment, and have response data available in the patient chart. Data collected included patient demographics, clinical characteristics, and treatments received prior to and concomitantly with ECP. Clinical outcomes were collected every 3 months during treatment for up to 18 months, and included the body surface area (BSA) affected, appearance of new skin lesions, and the physician-rated Clinical Global Impression-Improvement (CGI-I) scores. Response to ECP was defined as >50% reduction in BSA affected at any point during the follow-up period, consisting of the time from ECP initiation through the time of data collection. Data analysis was descriptive in nature.RESULTSFour clinical sites participated in the study and enrolled a total of 26 patients for the interim analysis. Patients were predominantly female (53.8%) and White (88.5%). Mean age at CTCL diagnosis was 68.4 years, and the majority patients were diagnosed with Sézary syndrome (57.5%) or mycosis fungoides (30.8%). Nearly half of patients (46.1%) had stage IV disease at diagnosis (IVA, 26.9%; IVB, 19.2%) and half of patients (50.0%) had lymph node involvement at diagnosis. Median BSA involvement with plaques/patches at diagnosis was 80% (interquartile range [IQR], 20% to 90%). Six patients (23.1%) achieved >50% reduction in BSA affected, and among those, median time to response was 6.0 months (IQR, 2.9 to 15.0 months). New skin lesions appeared in 5 patients (19.2%). Among those with available data, the percentage of patients rated as minimally improved, much improved, or very much improved on the CGI-I was 57.7% at 3 months (N=26), 50.0% at 6 months (N=18), and 60.0% at 9 months (N=15) after ECP initiation.CONCLUSIONSThis retrospective observational study describes patient characteristics and clinical outcomes among CTCL-diagnosed patients initiating therapy with ECP. Despite the population treated with ECP in real-world practice being older and having more advanced-stage disease compared to recent clinical trials, response rate was comparable. DisclosuresGirardi: Transimmune: Patents & Royalties: Inventor/IP; Helsinn: Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Research Funding; Soligenix: Research Funding; Mallinckrodt Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Stradefy Biosciences Inc: Patents & Royalties: Inventor/IP; Actelion: Membership on an entity's Board of Directors or advisory committees, Research Funding. Huang: Mallinckrodt Pharmaceuticals: Current Employment. Corman: Mallinckrodt Pharmaceuticals: Consultancy. Edmundson: Mallinckrodt Pharmaceuticals: Consultancy. Kale: Mallinckrodt Pharmaceuticals: Consultancy. Rusibamayila: Mallinckrodt Pharmaceuticals: Consultancy. Foss: Kura: Honoraria; Daiichi Sankyo: Honoraria; Seattle Genetics: Honoraria, Speakers Bureau; Acrotech: Honoraria, Speakers Bureau; Mallinckrodt: Honoraria; Kyowa: Honoraria.

Topical epigallocatechin-3-gallate in the treatment of vitiligo.

To preliminarily assess the efficacy and safety of the topical application of Epigallocatechin-3-gallate (EGCG) in treating vitiligo, a 6-month clinical trial was carried out. Patients were randomly given topical application of EGCG on the assigned lesions, with pimecrolimus being used as the control for twice a day over a 6-month treatment period. Responses to treatment were assessed based on the changes in VASI score for percentage reduction in body surface area and the PGA scores. According to our results, both drugs were discovered to be markedly effective on repigmentation. The VASI of lesion had diminished from 1.19±0.42 to 0.63±0.38, in the EGCG-treated lesions, while from 1.18±0.43 to 0.61±0.36 in the pimecrolimus-treated lesions, and there was no statistically significant difference in VASI score between the EGCG-treated lesions and pimecrolimus-treated lesions (P=0.755). Meanwhile, the mean PGA score on the EGCG applied side was 4.39±2.23, while that was 4.43±2.02 on the pimecrolimus applied side (P=0.886). Furthermore, difference in the improvement degree between pimecrolimus side and EGCG side was not statistically significant (P=0.845). Notably, no serious side effects were observed throughout the study. Findings of the study indicate that topical EGCG can be effective on treating vitiligo.

AGGRESSIVE WEIGHT LOSS PROGRAM WITH A KETOGENIC INDUCTION PHASE FOR THE TREATMENT OF CHRONIC PLAQUE PSORIASIS

Chronic plaque psoriasis is an inflammatory skin disease associated with obesity,characterized by low-grade inflammation. Weight loss (WL) has been demonstrated to reduce psoriasis severity and inflammation. Very low-calorie ketogenic diet (VLCKD) has been associated with a significant reduction in visceral adipose tissue and keton bodies likely have anti-inflammatory proprieties. We evaluate the efficacy of an aggressive WL program with a ketogenic induction phase as first-line treatment of chronic plaque psoriasis. We conducted a single-arm trial conducted (NCT03531528). Adult overweight/obese patients (N=37)with stable chronic plaque psoriasis underwent a 10-week two-phase WL program consisting in a 4-week protein-sparing, VLCKD (<500 kcal/day; 1.2 grams of protein/kg of ideal body weight/day) and a 6-week balanced, hypocaloric (25-30 kcal/kg of ideal body weight/day), low glycemic index, Mediterranean-like diet. The primary endpoint was the reduction in the Psoriasis Area and Severity Index (PASI) at week 10. Major secondary endpoints included:improvement of PASI 50% and 75%,reduction in body surface area (BSA) involved,improvement of itch severity (visual-analogue scale) and Dermatology Life Quality Index (DLQI) at week 10. With a mean body weight reduction of 12.0%,dietary intervention resulted in a significant reduction in PASI: mean change, -10.6 [95%CI, -12.8 to -8.4] (P<0.001). A reduction in PASI 50% and 75% was recorded in 36 (97.3%) and 24 (64.9%) patients, respectively. Treatment resulted also in a significant reduction of BSA involved and an improvement in itch severity and DLQI (P<0.001 for all). In adult overweight patients with stable chronic plaque psoriasis an aggressive dietary WL program consisting in a ketogenic regimen followed by a balanced, hypocaloric Mediterranean-like diet appeared an efficacious first-line strategy for improving disease severity. Comparative studies with other dietary regimens and long-term efficacy data are warranted.

Increased Trend of Cosmetic Procedures in Patients With Psoriasis Who Attain 75% or Greater Improvement.

Background: The relationship between the clearance of psoriasis and improved quality of life together with an increased uptake of cosmetic procedures has not been reported to date. Objective: A survey was conducted at a single dermatology center to determine if there was an increased trend in cosmetic procedures in patients with moderate to severe psoriasis who attained 75% or greater reduction of the body surface area (BSA) with biologic agents and oral systemic therapies, and if this was related to an improvement in quality of life following psoriasis clearance. Study Design: In this case series, 138 patients with a history of moderate to severe psoriasis who attained 75% or greater body surface area (BSA) reduction with biologic agents or oral systemic therapies and had undergone at least one cosmetic procedure in the past 2 years were surveyed. Patient characteristics were collected including age, sex, percent BSA at initiation of therapy, the class of biologic or oral systemic therapies, and the different types of cosmetic procedures. Patients were asked to answer a 5-question survey on quality of life improvement, satisfaction with treatment, and correlation with the cosmetic procedure they had undergone, Patients also completed the Dermatology Quality of Life Index (DLQI) questionnaire in the survey. Results: The majority of patients who had undergone a cosmetic procedure after achieving 75% BSA stated that their psoriasis had previously prevented them from undergoing a cosmetic procedure. Regardless of therapy, all patients felt their quality of life had improved as a result of their treatment, and 91% of patients stated this was the impetus to undergo a cosmetic procedure. The mean DLQI score prior to therapy was 14.3 and 71% of patients reported a DLQI score of 0/1 after their psoriasis improved. Conclusion: There was a correlation between improvement in quality of life in patients who had achieved at least a 75% reduction in BSA with either a biologic agent, oral agent, or both, and the uptake of cosmetic procedures. J Drugs Dermatol. 2020;19(8): doi:10.36849/JDD.2020.5104R1.

Therapeutic Potential of Lebrikizumab in the Treatment of Atopic Dermatitis.

BackgroundAtopic dermatitis (AD) is a chronic, relapsing skin condition with a wide disease spectrum. Moderate-to-severe cases often need systemic treatment. Conventional immunosuppressants have extensive side effect profiles and require close monitoring. In recent decades, there has been increasing interest in developing targeted systemic immunomodulators for AD, as they have been shown to have efficacy for AD as well as favorable safety profiles. Herein, we review the recent data on lebrikizumab, an interleukin (IL)-13 inhibitor, and its potential role in the treatment of AD.ObjectiveReview the mechanism of action, and available data on the efficacy and safety of lebrikizumab for the treatment of AD.MethodsPubMed, Google Scholar, and clinicaltrials.gov searches were performed with the following terms: “atopic dermatitis,” “dermatitis,” “eczema,” “lebrikizumab,” “IL-4,” and “IL-13.”ResultsTwo Phase II randomized controlled clinical trials have been conducted to evaluate the use of lebrikizumab in a total of 289 patients with moderate-severe AD and inadequate response to topical corticosteroids. Patients treated with lebrikizumab experienced significantly more improvement in their AD compared to placebo, as measured by Eczema Area and Severity Index (EASI)-50 and EASI-75 scores, pruritus scores, and reduction in body surface area (BSA). Its clinical efficacy appears to be dose-dependent, and it has a favorable side effect profile and is generally well tolerated.ConclusionLebrikizumab appears to be a promising emerging targeted biologic for the treatment of moderate-to-severe AD. Further Phase III studies investigating optimal dosing regimens and safety profile are needed.

Interventions for infantile seborrhoeic dermatitis (including cradle cap).

Interventions for infantile seborrhoeic dermatitis (including cradle cap).

Evaluation of psoriasis patients' attitudes toward benefit-risk and therapeutic trade-offs in their choice of treatments.

ObjectiveTreatment options for psoriasis offer trade-offs in terms of efficacy, convenience, and risk of adverse events. We evaluated patients’ preferences with respect to benefit–risk in the treatment of psoriasis.MethodsA discrete choice experiment was conducted in adults from the UK with moderate-to-severe psoriasis using an orthogonal design with 32 hypothetical choice sets. Participants were randomly assigned to one of two surveys with 16 choice sets. Patients’ preferences were investigated with respect to the following attributes: reduction in body surface area affected by psoriasis, treatment administration (frequency and mode of delivery), short-term diarrhea or nausea risk, and 10-year risk of developing melanoma or nonmelanoma skin cancer, tuberculosis, or serious infections. A mixed effects logistic regression model generated relative preferences between treatment profiles.ResultsParticipants (N=292) had a strong preference to avoid increased risk of melanoma or nonmelanoma skin cancer (odds ratio [OR]: 0.44 per 5% increased 10-year risk) and increased risks of tuberculosis and serious infections (both ORs: 0.73 per 5% increased 10-year risk) and preferred once-weekly to twice-daily tablets (OR: 0.76) and weekly (OR: 0.56) or fortnightly (OR: 0.65) injections. Participants preferred avoiding treatments that may cause diarrhea or nausea in the first 2 weeks (OR: 0.87 per 5% increase) and preferred treatments that effectively resolved plaque lesions (OR: 0.93 for each palm area still affected).ConclusionAll attributes were significant predictors of choice. Patients’ preference research complements clinical trial data by providing insight regarding the relative weight of efficacy, tolerability, and other factors for patients when making treatment choices.

Core Temperature in Service Members With and Without Traumatic Amputations During a Prolonged Endurance Event.

Service members with traumatic amputations may be at an increased risk of elevated core body temperature, since their ability to dissipate heat may decrease with the reduction in body surface area (BSA) after injury. Elevated core temperature can impair physical performance during combat operations potentially putting the service members and their teams at risk. The purpose of this study was to compare core temperature between individuals with and without amputations during a prolonged endurance event. Twenty healthy male military service members (10 with amputations, 10 without) participated in the Bataan Memorial Death March 26.2-mile event on March 27, 2011. Data collected include BSA, body mass index, body composition, body weight before and after the event, core temperature during the event, and postevent hydration status. Body composition was measured by dual-energy X-ray absorptiometry. Body weight was measured by digital scale. Core temperature was measured by ingestible sensor. Hydration was measured by urine specific gravity. The Walter Reed Army Medical Center Institutional Review Board approved this study and participants provided written informed consent. Three participants' data were not included in the analyses. No significant differences in core temperature were found between participants in both groups, and no correlation was found between core temperature and either BSA or hydration status. There was no significant difference in maximal core temperature between the groups (p = 0.27). Nearly all participants (8 control, 6 amputation) reached 38.3°C, the threshold for increased risk of heat exhaustion. No subjects reached 40.0°C, the threshold for increased risk of heat stroke. Time spent above the 38.3°C threshold was not significantly different between groups, but varied widely by participant in relation to the duration of the event. Participants without amputations finished the event faster than participants with amputations (7.9 ± 1.4 vs. 9.6 ± 0.96, p < 0.01), possibly indicating that participants with amputations self-selected a slower pace to attenuate increased core temperature. Until conclusive evidence is accumulated, it is prudent for military leaders, trainers, and military service members to closely monitor this population during physical activity to prevent heat injuries.

The Role of Fcγ Receptor Polymorphisms in the Response to Anti–Tumor Necrosis Factor Therapy in Psoriasis

Variability in genes encoding proteins involved in the immunological pathways of biological therapy may account for the differences observed in outcomes of anti–tumor necrosis factor (TNF) treatment of psoriasis. To assess the role of 2 Fcγ receptor (FcγR) polymorphisms in the response to anti-TNF therapy in psoriasis. Retrospective series of patients with psoriasis who received anti-TNF therapy(infliximab, adalimumab, or etanercept) from January 1, 2007, through December 31, 2010. Patients were followed up for 12 weeks. Two psoriasis referral centers. Seventy treatment-naive patients with moderate to severe psoriasis who received anti-TNF agents. Patients underwent FcγRIIA-H131R and FcγRIIIA-V158F polymorphism genotyping. The Psoriasis Area and Severity Index and the body surface area were assessed at baseline and at treatment weeks 6 to 8 and 12. The polymorphism genotypes were correlated with the treatment outcomes. Bivariate analysis showed a nonsignificant association between FcγR low-affinity genotypes and greater improvement in the Psoriasis Area and Severity Index and body surface area at the end of treatment. Conversely, patients harboring high-affinity alleles presented a greater reduction in body surface area at the intermediate point, which remained independent in the multivariate analysis. We also detected an additive effect of both polymorphisms in the multivariate analysis. High-affinity alleles may contribute to a quicker response owing to a more efficient removal of relevant cells expressing TNF. Preliminary results of this pilot study on the pharmacogenetics of FcγR and biological therapy in psoriasis suggest a role with clinical implications for FcγRIIA-H131R and FcγRIIIA-V158F polymorphisms in the outcome of anti-TNF treatment of psoriasis. These results might help dermatologists in guiding therapeutic decisions, especially in very severe cases where a quick response is needed.

Comparison of efficacy and side‐effect profile of oral PUVA vs. oral PUVA sol in the treatment of vitiligo: a 36‐week prospective study

Both Oral PUVA and PUVA sol have been successfully used in vitiligo treatment. However, there is paucity of studies comparing the two therapies, especially under subtropical conditions of abundant sunlight where PUVA sol is more feasible. To compare the efficacy and side effects of oral PUVA versus oral PUVA sol therapy in generalized vitiligo. Comparative prospective clinical trial conducted on consecutive patients of generalized vitiligo. Response to treatment was assessed using change in Lund & Browder (L & B) score for assessment of reduction in body surface area of involvement, patient global assessment (PGA) of improvement in vitiligo, investigator's global assessment (IGA) of extent of repigmentation, and quality of life (QOL) assessment using Tjioe et al questionnaire. Thirty five patients were recruited- 18 in PUVA and 17 in PUVA sol group. Mean percentage change in L & B score at 36 weeks was 46.4% in PUVA and 26.1% in PUVA sol group (P = 0.06), mean PGA score in PUVA was 4.58 ± 2.23 and in PUVA sol group was 6 ± 2.08 (P = 0.13), mean IGA score was 3.08 ± 1.68 in PUVA and 1.79 ± 0.57 in PUVA sol group (P = 0.11). QOL scores were significantly higher in PUVA group as compared to the PUVA sol group (P = 0.04). Side effects were comparable in two groups except for phototoxic side effects which were significantly more in PUVA group. PUVA is more efficacious than PUVA sol and also provides greater psychological benefit in treatment of generalized vitiligo but is associated with more phototoxic adverse effects.

A Dead Sea Water-Enriched Body Cream Improves Skin Severity Scores in Children with Atopic Dermatitis

Dead Sea (DS) mud and water are known for their unique composition of minerals, and for their therapeutic properties on inflammatory skin diseases. The objective of the study was to evaluate the efficacy of an emollient cream enriched with DS water in children with atopic dermatitis (AD). Eighty six AD children were randomized in a double-blind controlled study to receive twice-daily topical treatment with a body cream enriched with DS minerals (TP) compared to two types of control: 1) DM, DS minerals with lower DS water concentrations than TP, and 2) an emollient (E) with no DS minerals. Efficacy was assessed by a change in clinical skin severity scores: SCORing Atopic Dermatitis (SCORAD), investigator’s global assessment (IGA) and patient global assessment (PGA) as well as by objective physiological parameters: transepidermal water loss (TEWL), stratum corneum hydration (SCH), affected body surface area (BSA) and Objective Severity Assessment of Atopic Dermatitis (OSAAD). The total length of the trial was 12 weeks divided to 6 visits at weeks 0, 2, 4, 6, 8, 12. The study showed that both TP and DM creams improved OSAAD scores. Only TP improved TEWL and SCH. TP was the most effective regarding TEWL, SCH and OSAAD compared to DM and E. Treatment with E decreased more significantly IGA score compared to TP. Although within each treatment group significant improvements in SCH, BSA, SCORAD, IGA and PGA were observed, the reduction in BSA, SCORAD and PGA was not significantly different among the groups. Our results clearly show the benefits of TP as a leave on-skin emulsion enrich with DS water in terms of skin barrier function. Thus, TP can serve as an effective adjuvant treatment for AD skin as well as for its maintenance.

Dose reduction of chemotherapeutic agents after weight loss.

The aim of dose reduction of chemotherapeutic agents following weight loss is to avoid excessive toxicity while maintaining an equivalent therapeutic effect. Several methods of calculating this dose reduction are currently in use, including dose reduction in proportion to the reduction in body surface area (BSA) or the amount of weight lost and no dose reduction unless significant toxicity occurs. Each of these methods results in the administration of a different dose and therefore different drug exposure, as measured by the area under the time versus concentration curve (AUC). We have used pharmacokinetic modeling software and normative data on the pharmacokinetics of high-dose methotrexate to determine the change in AUC resulting from dose reduction by each of the methods cited for patients with weight loss. Dose reduction in proportion to the reduction in weight results in the same AUC and therefore equivalent drug exposure as before weight loss. In contrast, the more common practice of dose reduction in proportion to the decrease in BSA (as determined by recalculating BSA) results in a higher AUC than before weight loss. This results in increased drug exposure and potentially increased toxicity, which may be avoided if dose reduction is carried out in proportion to the decrease in weight rather than in BSA. The same principles are applicable to other drugs, particularly those associated with dose-dependent toxicity.

Cyclosporine as maintenance therapy in patients with severe psoriasis

Low-dose cyclosporine therapy for severe plaque psoriasis is effective. Most side effects can be controlled by patient monitoring, with appropriate dose adjustment or pharmacologic intervention, or both, if indicated. Prevention or reversibility of laboratory and chemical abnormalities may be achieved by discontinuation of therapy after the induction of clearing. However, relapse occurs rapidly on discontinuation. Maintenance therapy with cyclosporine after induction has not been fully evaluated. Our purpose was to compare a regimen of 3.0 mg/kg per day of oral cyclosporine with placebo in maintaining remission or improvement in patients with psoriasis. After a 16-week unblinded induction phase in which 181 patients received cyclosporine, 5.0 mg/kg per day (an increase up to 6.0 mg/kg per day and a decrease to 3.0 mg/kg per day were allowed, if required, to achieve efficacy or tolerability, respectively), those patients showing a 70% decrease or more in involved body surface area (BSA) entered the 24-week maintenance phase and were randomly assigned to either placebo, cyclosporine, 1.5 mg/kg per day, or cyclosporine, 3.0 mg/kg per day. Patients were considered to have had a relapse when BSA returned to 50% or more of the prestudy baseline value. Clinical efficacy, adverse effects, and laboratory values were monitored regularly throughout both study phases. During induction, cyclosporine at approximately 5.0 mg/kg per day produced a reduction in BSA of 70% or more in 86% of the patients. During maintenance, the median time to relapse was 6 weeks in both the placebo and cyclosporine 1.5 mg/kg per day groups, but was longer than the 24-week maintenance period in the 3.0 mg/kg per day group (p < 0.001 vs placebo). By the end of the maintenance period, 42% of the patients in the 3.0 mg/kg per day cyclosporine group had a relapse compared with 84% in the placebo group. Changes in laboratory values associated with the higher induction dosage generally exhibited partial or complete return toward mean prestudy baseline values during the maintenance phase, with the greatest degree of normalization in the placebo group. Cyclosporine, 3.0 mg/kg per day, adequately and safely maintained 58% of patients with psoriasis for a 6-month period after clearing of their psoriasis with doses of approximately 5.0 mg/kg per day.

Variation in the practice of dose reduction of chemotherapeutic agents after weight loss or amputation.

Dose reduction of chemotherapeutic agents in response to weight loss or amputation is important in avoiding excessive therapy-related toxicity. Several methods of calculating this dose reduction are currently in use, including dose reduction in proportion to (a) the reduction in body surface area (BSA), (b) the amount of weight lost, and (c) no dose reduction unless toxicity is observed. Each of these methods results in the administration of a different dose, and few guidelines exist as to the preferred method. We conducted a survey of a large group of pediatric oncologists, pediatric oncology nurses, and data managers to determine the methods of dose reduction currently in use for patients (a) with weight loss, (b) after amputation, and (c) with further weight loss after amputation. Responses were obtained from 237 of 294 individuals surveyed (80.6%). The most popular method was to dose reduce in proportion to the reduction in BSA in patients with weight loss alone (88%), amputees (60%), and amputees with ongoing weight loss (66%). Other methods were chosen by 7%, 31%, and 24% of participants in each of these clinical settings, respectively. The chosen methods result in a discrepancy of administered doses of up to 37%. Our results highlight the need for the standardization of practice, and the determination of the optimal method of dose reduction after weight loss or amputation.