Real-Life Effectiveness of Apremilast for the Treatment of Psoriasis in Belgium: Results From the Observational OTELO Study.

INTRODUCTION: Apremilast is approved for the treatment of psoriasis and psoriatic arthritis. However, data on the efficacy and safety of apremilast in clinical practice are limited. We assessed the real-world use and effectiveness of apremilast in patients with moderate to severe plaque psoriasis visiting dermatologist practices in Belgium, from the perspectives of the patient and the physician. METHODS: This prospective observational study enrolled adults aged 18 years or more initiating apremilast between 6 April 2017 and 30 June 2018, per Belgian reimbursement criteria. Primary outcome was the Patient Benefit Index for Skin Diseases (PBI-S). Secondary outcomes included the Patient Global Assessment (PtGA), Dermatology Life Quality Index (DLQI), Psoriasis Area and Severity Index (PASI), and body surface area (BSA). Patients were followed up for up to 18 months. RESULTS: Overall, 122 enrolled patients received at least one dose of apremilast, of which 89 received treatment for more than 150 days and were included in the reference population. Treatment goals most frequently identified (at least 70% of patients) as "very important" in the PBI-S were related to physical impairments. After 6 months of apremilast treatment, 61-78% of patients reported they had achieved these goals; only 12.5% assessed their disease as severe (PtGA, 53.6% at apremilast initiation) and over half reported a DLQI score of 5 or less, indicating improved quality of life. As assessed by the physician, 68.4% and 35.1% of patients achieved at least a 50% and 75% reduction in PASI, respectively, at month 6. Apremilast was well tolerated with no new safety signals identified. CONCLUSIONS: Our real-world data indicate that apremilast fulfils the expectations of Belgian patients with moderate to severe psoriasis, and from the perspectives of both the patient and physician, apremilast has a positive impact on their disease. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT03097003.

Long-term topical management of psoriasis: the road ahead.

Topical therapies have been available for the treatment of psoriasis for several decades. Despite this and the availability of several types of topicals, with varying potency, and numerous vehicles of administration, the majority of clinical data and guidance is on short-term use in the management of psoriasis. The aim of this manuscript is to review the unmet needs that exist in the long-term management of psoriasis and provide the dermatology community with an understanding that a treatment regimen with topical therapies could be the best treatment option at least for some phases of this chronic relapsing disease. We present a 'call to action' on the need for clinical alignment on terminology in the field and recommend the term 'long-term management' be adopted as the most appropriate in the context of this manuscript. This expert opinion report provides a detailed review of the limited evidence available regarding long-term use of topical therapies for the management of psoriasis, alongside our key considerations and recommendations to assist dermatologists with the implementation of topicals as part of long-term management strategies. Long-term management should be considered mandatory to ensure patients receive appropriate proactive treatment which may help optimize adherence and long-term outcomes.

General practice recommendations for the topical treatment of psoriasis: a modified-Delphi approach.

BACKGROUND: Although GPs are usually the first port of call for patients with psoriasis, there is a lack of consistent and up-to-date clinical recommendations for interventions for patients with mild-to-moderate disease. AIM: To provide practical recommendations for GPs to optimise psoriasis treatment with topical therapies in four key areas: patient identification; treatment decision making with topical theory; topical treatment outcomes; and optimising patient adherence. DESIGN & SETTING: A consensus-seeking programme (modified-Delphi approach) was undertaken to assess the literature and develop recommendations for GPs, based on evidence and expert opinion. METHOD: Three dermatologists compiled 47 questions that were subsequently ranked and refined according to clinical relevance or importance using an online survey. Thereafter, 19 dermatologists from different European countries developed statements and clinical recommendations for the top seven ranked topical treatment and GP-relevant questions based on literature research and clinical experience. The final recommendations were based on 100% agreement among a final panel of seven experts. RESULTS: The clinical effectiveness, fast onset of action, tolerability, cosmetic acceptability, and practicability of topical therapy, in addition to good physician-patient communication, are important for optimising patient adherence and maximising efficacy. Topical treatments combining corticosteroids and vitamin D analogues (administered as fixed combination) are well-established first-line treatments in mild-to-moderate psoriasis. CONCLUSION: Simple but detailed practical guidance is provided, which is formed from evidence and expert clinical recommendations, to assist GPs with the optimal use of topical agents based on efficacy, tolerability, disease severity, site of psoriasis, patient lifestyle and preferences, and intended duration of treatment.

Management of EGFR Inhibitor-induced Skin Toxicity and Factors Impacting Patients' Adherence to Skin Toxicity Treatment: Health Care Provider and Patient Surveys in European Oncology Centers.

INTRODUCTION: This study aimed to provide a description of existing measures for the prevention and management of epidermal growth factor receptor inhibitor monoclonal antibody-induced skin toxicities and factors impacting patients' adherence to those measures in France, Germany, and Spain. MATERIALS AND METHODS: The study consisted of 2 separate surveys. Health care professionals (HCPs; oncologists and nurses) in France, Germany, and Spain were interviewed, and patients with metastatic colorectal cancer and head-and-neck cancer in France and Germany self-completed questionnaires. The study was conducted between February and July 2018. RESULTS: A total of 53 oncologists, 44 nurses, and 143 patients participated in the study. HCPs stated that skin toxicities moderately (52%) or severely (28%) impacted patient care. Ninety percent of HCPs reported routine provision of prophylactic measures. The great majority of patients self-reported adherence with the prophylactic (80% to 88% depending on the type of measures) and reactive (93% to drug prescription) skin toxicity recommendations. HCPs estimated patient adherence to be 45% for full adherence and 40% for partial adherence. Most HCPs reported a positive or very positive impact of preventive measures and recommendations on skin toxicity incidence and severity, patients' quality of life, and various aspects of quality of anti-cancer treatment. CONCLUSIONS: Skin toxicities are an important adversity negatively impacting on patient care. However, despite the positive perception of the effectiveness of skin toxicity prophylaxis, almost one-third of oncology centers did not provide formal guidelines, and 10% of HCPs did not provide routine prophylactic measures. Patient adherence appears to be high for epidermal growth factor receptor inhibitor monoclonal antibody-induced skin toxicity prevention measures.

Optimizing Anti-Inflammatory and Immunomodulatory Effects of Corticosteroid and Vitamin D Analogue Fixed-Dose Combination Therapy.

Fixed-dose combination topical therapy with corticosteroid and vitamin D analog provides effective treatment and possible long-term management of psoriasis. The anti-inflammatory and immunomodulatory effects of corticosteroids and vitamin D analogs in treating psoriasis are well investigated; their complementary effects lead to the disruption of the inflammatory feedback loop underlying psoriasis pathogenesis. Recent preclinical data showed that combination therapy is more effective than monotherapies of the active ingredients in preventing activation of resting pro-inflammatory cells, inducing immunomodulation, reducing inflammatory responses by regulating T cell production, and normalizing keratinocytes. The increased understanding of the mechanism of action of fixed-dose combination therapy from preclinical studies is supported by several clinical studies. As the efficacy of topical therapy is correlated with the skin penetration of the active ingredients, new drug delivery systems have been developed. The fixed-dose combination Cal/BD aerosol foam creates a modified supersaturated formulation when applied to the skin, which is maintained for at least 26 h in the laboratory setting. Clinical studies have demonstrated superior efficacy of fixed-dose combination calcipotriol (Cal) 50 µg/g and betamethasone dipropionate (BD) 0.5 mg/g aerosol foam compared with monotherapies of the active ingredients. Furthermore, Cal/BD aerosol foam has shown significantly improved efficacy compared with more traditional formulations, such as Cal/BD ointment and gel, in other studies. Calcipotriol also mitigates risks associated with betamethasone dipropionate and vice versa, resulting in the favorable safety profile observed with fixed-dose combination treatment. Recent data also suggest that fixed-dose combination treatment could provide long-term management of psoriasis, although further clinical investigations are needed. Overall, these data support the value of fixed-dose combination therapy of corticosteroid and vitamin D analog and highlight the added potential of innovative drug delivery for the treatment of psoriasis. FUNDING: LEO Pharma.

Clinical Signs, Pathophysiology and Management of Cutaneous Side Effects of Anti-Tumor Necrosis Factor Agents.

Approximately one in four patients treated with anti-TNF agents (infliximab, etanercept, adalimumab, certolizumab, and golimumab) develops cutaneous adverse events, typically months to years after the initiation of treatment, with xerosis cutis, eczema (often psoriasiform), psoriasis, palmoplantar pustulosis, cutaneous infections, alopecia, and skin cancer being the most frequently encountered. The typical skin lesion of anti-tumor necrosis factor (TNF)-treated patients is orange-red psoriasiform eczema affecting the flexures, genitalia, scalp, or face, with high susceptibility to bacterial superinfection with Staphylococcus aureus. When adequate dermatological treatment is administered to patients with skin lesions receiving anti-TNF treatment, the discontinuation of anti-TNF agents is only rarely required. Smoking, female sex, and Crohn's disease are most frequently observed as risk factors for anti-TNF-induced cutaneous adverse events. The underlying pathophysiology is still poorly understood, but epidermal permeability barrier dysfunction, increased susceptibility to bacterial superinfection, and cytokines derived from T helper (Th) 1 (interferon-γ), Th17 cells (interleukin [IL]-17A and IL-22), plasmocytic dendritic cells (interferon-α), and keratinocytes (IL-36γ and IL-17C) appear to play a role. In this review, we describe the clinical characteristics, risk factors, pathophysiology, and management of cutaneous adverse events of patients treated with anti-TNF agents. In addition, we try to give some practical guidance on how to prevent and manage the skin changes in anti-TNF-treated patients, based on our own experience with dermatological care in a large cohort of inflammatory bowel disease patients receiving anti-TNF therapy.

Management of adverse events during treatment of gastrointestinal cancers with epidermal growth factor inhibitors.

The epidermal growth factor receptor (EGFR) is involved in development and progression of some gastrointestinal cancers, and is targeted by monoclonal antibodies (mAbs) and tyrosine kinase inhibitors (TKIs) used to treat these conditions. Targeted agents are generally better tolerated than conventional chemotherapy, but have characteristic toxicities that can affect adherence, dosing, and outcomes. Skin conditions are the most common toxicities associated with EGFR inhibitors, particularly papulopustular rash. Other common toxicities include mucosal toxicity, electrolyte imbalances (notably hypomagnesaemia), and diarrhoea, while the chimaeric mAb cetuximab is also associated with increased risk of infusion reactions. With appropriate prophylaxis, the incidence and severity of these events can be reduced, while management strategies tailored to the patient and the degree of toxicity can help to ensure continuation of anti-cancer therapy. Here, we review the main toxicities associated with EGFR-inhibiting mAbs and TKIs in patients with gastrointestinal cancers, and provide recommendations for prophylaxis and treatment.

Current Practice of Therapeutic Drug Monitoring of Biopharmaceuticals in Psoriasis Patients.

The high prevalence of psoriasis and the high spending on pharmaceuticals motivate a more evidence-based and cost-effective usage of biopharmaceuticals. A growing body of evidence exists that the implementation of therapeutic drug monitoring for biopharmaceuticals in psoriasis patients optimizes patient management and clinical outcome and enhances their efficacy. Therefore, the aim of this review was to give an overview of the literature on therapeutic drug monitoring of biopharmaceuticals in the treatment of psoriasis and to provide the useful information to dermatologists to improve health care in psoriasis patients.

The association between etanercept serum concentration and psoriasis severity is highly age-dependent.

The association between etanercept serum concentration and psoriasis disease severity is poorly investigated, and currently etanercept serum concentration monitoring that is aiming to optimize the psoriasis treatment lacks evidence. In this prospective study, we investigated the relation between etanercept exposure and disease severity via measuring etanercept concentrations at five consecutive time points in 56 psoriasis patients. Disease severity assessments included the Psoriasis Area and Severity Index (PASI), body surface area (BSA) and Physician Global Assessment (PGA), and etanercept and anti-etanercept antibody concentrations were determined every 3 months for a period of 1 year. The present study demonstrated that the association between etanercept concentration and psoriasis severity is age-dependent: when patients were stratified into three groups, patients in the youngest age group (-50 years) showed a lower PASI at a higher etanercept concentration (ß = -0.26), whereas patients in the oldest age group (+59 years) showed the opposite trend (ß =0.22). Similar age effects were observed in the relation of etanercept concentration with BSA (P=0.02) and PGA (P=0.02). The influence of age and length of time in therapy on the etanercept concentration-disease severity relation was unaffected by body mass index (BMI) or any other possible confounder. Incidence of anti-etanercept antibodies was low (2%). The age-dependent relation between etanercept serum concentrations is both unexpected and intriguing and needs further investigation.

Recommendations for managing a suboptimal response to biologics for moderate-to-severe psoriasis: A Belgian perspective.

Over the past decade, biologics have become the gold standard in the treatment of moderate-to-severe psoriasis for patients who have failed or who have contraindications to traditional systemic treatments. However, although practical recommendations on how to treat a suboptimal response to biologics exist in other chronic inflammatory diseases, they are only just beginning to emerge for psoriasis. This article aims to formulate recommendations in the case of a suboptimal response of psoriasis to biologics in the Belgian setting. A Belgian taskforce of psoriasis experts was convened to review the results of a literature search and formulate recommendations based on the available evidence and provide expert opinion to address gaps in the evidence. The taskforce has proposed a treatment algorithm for patients with a primary non-response or a secondary loss of response to help address an unmet need. Expert recommendations have been developed to address treatment strategies in case of a primary or secondary suboptimal response to biologics in the treatment of moderate-to-severe psoriasis in Belgium.

Characteristics of Skin Lesions Associated With Anti-Tumor Necrosis Factor Therapy in Patients With Inflammatory Bowel Disease: A Cohort Study.

BACKGROUND: A subgroup of patients with inflammatory bowel disease (IBD) treated with anti-tumor necrosis factor (TNF) antibodies develop skin lesions, but the lesions and their clinical course are not well-characterized. OBJECTIVE: To describe patients treated with anti-TNF antibodies who did and did not develop skin lesions. DESIGN: Retrospective cohort. SETTING: Single IBD tertiary referral center. PATIENTS: 917 consecutive patients with IBD who initiated anti-TNF therapy. MEASUREMENTS: Skin lesions, patient demographic characteristics, treatments, clinical course, and serologic and genetic markers. RESULTS: During a median follow-up of 3.5 years (interquartile range [IQR], 0.5 to 7.4 years), skin lesions associated with the use of anti-TNF therapy developed in 264 of 917 (29%) patients (psoriasiform eczema, 30.6%; eczema, 23.5%; xerosis cutis, 10.6%; palmoplantar pustulosis, 5.3%; psoriasis, 3.8%; other, 26.1%). Lesions typically developed at flexural regions, genitalia, and the scalp, especially the psoriasiform lesions. Thirty-one percent of women and 26% of men developed lesions. Median cumulative doses (2864 mg/y [IQR, 2203 to 3819 mg/y] and 2927 mg/y [IQR, 2377 to 3667 mg/y]) and trough levels (4.2 µg/mL [IQR, 2.6 to 5.8 µg/mL] and 4.0 µg/mL [IQR, 1.6 to 5.9 µg/mL]) of infliximab were similar in patients with and without lesions. All but 28 patients (11%) were successfully managed without needing to stop therapy because of lesions. LIMITATION: Retrospective nature and no matched control group of patients not receiving anti-TNF therapy. CONCLUSION: Skin lesions occur frequently in association with anti-TNF therapy but rarely require discontinuation of therapy. Close surveillance and early referral to a dedicated dermatologist are recommended. PRIMARY FUNDING SOURCE: Research Foundation Flanders (FWO), Belgium; Geconcerteerde Onderzoekacties of KU Leuven; and Janssen Biologics.

An observational study of the real-life management of psoriasis patients treated with etanercept according to the new reimbursement criteria (in Belgium).

BACKGROUND: This study described the number of patients with psoriasis receiving flexible (continuous/intermittent) dosing with etanercept (ETN) and the real-world economic impact. METHODS: BeFlex was a prospective, observational study with a ≥1 year follow-up. Patients ≥18 years with moderate-to-severe psoriasis who were starting or re-starting treatment with ETN in alignment with Belgian reimbursement criteria were included. Cost of ETN was compared with cost of adalimumab, ustekinumab and infliximab using estimates from the National Institute for Sickness and Disability Insurance (INAMI/RIZIV). RESULTS: In the flexible-dosing cohort (n = 121 with dose-regimen data), 66% were treated continuously and 34% intermittently. Baseline characteristics were similar across dosing cohorts. In the per-protocol cohort (n = 138), average ETN treatment duration/year was 40 weeks; 43 weeks continuous and 33 weeks intermittent. The overall mean interruption duration was 3.9 weeks/treatment cycle; 0.2 week continuous and 11.1 weeks intermittent. Mean dose/year was 2065 mg; 2182 mg continuous and 1660 mg intermittent. Flexible ETN dosing reduced the cost by 20% versus INAMI/RIZIV estimates. The theoretical cost of the other continuously-dosed biologics was 28-44% higher than that of flexible ETN. CONCLUSION: Approximately one-third of Belgian patients received intermittent ETN treatment. Flexible ETN dosing was more cost-effective than treatment with biologic agents that require continuous dosing.

The biological rationale for use of vitamin d analogs in combination with corticosteroids for the topical treatment of plaque psoriasis.

Topical corticosteroids and vitamin D analogs are well established as safe and effective first-line treatments for mild to moderate plaque psoriasis. They act via distinct and complementary mechanisms of action: vitamin D analogs primarily counter epidermal dysregulation, inhibiting epidermal hyperproliferation and inducing keratinocyte differentiation, whereas corticosteroids act primarily as immunosuppressors, targeting pro-inflammatory cytokines and chemokines. Furthermore, both agents have additional activity that may complement their main effects: vitamin D analogs have some immunomodulatory properties and corticosteroids may impact on keratinocyte differentiation. Based on their dominant mechanisms of action, there is a strong scientific rationale for the combination of corticosteroids and vitamin D analogs in the treatment of plaque psoriasis. Indeed, the combination has been shown to have a greater effect on the immune-mediated mechanisms of psoriasis than either monotherapy used alone. There is also a strong biological rationale for decreased side effects with the combination. Vitamin D may restore epidermal barrier function, which is impaired with corticosteroid use, and counteract steroid-induced skin atrophy. Corticosteroids may reduce perilesional skin irritation induced by vitamin D analogs. Although clinical data strongly support improved efficacy and tolerability with a combination of calcipotriol and betamethasone dipropionate, additional studies are needed to further investigate their underlying mechanisms.

Clinical improvement and satisfaction with biologic therapy in patients with severe plaque psoriasis: results of a European cross-sectional observational study.

BACKGROUND: Efficacy of biologic therapies for psoriasis has been demonstrated in randomized trials, but effectiveness in real-world settings has yet to be fully determined. OBJECTIVE: To compare clinical improvement and treatment satisfaction with biologic versus other therapies in patients with plaque psoriasis. METHODS: European dermatologists recruited psoriasis patients into an observational study. Dermatologists reported disease severity before and after starting current therapy; dermatologists and patients reported treatment satisfaction. RESULTS: These analyses included 2151 patients: topicals, n = 453; phototherapy, n = 666; conventional systemics, n = 683; biologics, n = 349. The percentage with severe disease declined from 70% before to 15% after biologics, a significantly greater decline than other therapies: topicals, 22-10%; phototherapy, 20-11%; conventional systemics, 49-15% (all p ≤ 0.03). Significantly more patients (59%) receiving biologics were satisfied with treatment versus topicals (45%), phototherapy (34%), or conventional systemics (50%) (all p < 0.001). Significantly more dermatologists were satisfied with biologics (60%) versus topicals (35%), phototherapy (26%), or conventional systemics (42%) (all p < 0.001). CONCLUSIONS: In this study, more patients receiving biologic therapies improved from severe to moderate or mild psoriasis than patients on other treatments. More patients with plaque psoriasis and their dermatologists were satisfied with biologics than any other treatment.

Dermatological side effects of hepatitis C and its treatment: patient management in the era of direct-acting antivirals.

Dermatological adverse events (AEs) are an existing concern during hepatitis C virus (HCV) infection and peginterferon/ribavirin treatment. HCV infection leads to dermatological and muco-cutaneous manifestations including small-vessel vasculitis as part of the mixed cryoglobulinemic syndrome. Peginterferon/ribavirin treatment is associated with well-characterized dermatological AEs tending towards a uniform entity of dermatitis. New direct-acting antivirals have led to significant improvements in sustained virologic response rates, but several have led to an increase in dermatological AEs versus peginterferon/ribavirin alone. In telaprevir trials, approximately half of treated patients had rash. More than 90% of these events were Grade 1 or 2 (mild/moderate) and in the majority (92%) of cases, progression to a more severe grade did not occur. In a small number of cases (6%), rash led to telaprevir discontinuation, whereupon symptoms commonly resolved. Dermatological AEs with telaprevir-based triple therapy were generally similar to those observed with peginterferon/ribavirin (xerosis, pruritus, and eczema). A few cases were classified as severe cutaneous adverse reaction (SCAR), also referred to as serious skin reactions, a group of rare conditions that are potentially life-threatening. It is therefore important to distinguish between telaprevir-related dermatitis and SCAR. The telaprevir prescribing information does not require telaprevir discontinuation for Grade 1 or 2 (mild/moderate) rash, which can be treated using emollients/moisturizers and topical corticosteroids. For Grade 3 rash, the prescribing information mandates immediate telaprevir discontinuation, with ribavirin interruption (with or without peginterferon) within 7 days of stopping telaprevir if there is no improvement, or sooner if it worsens. In case of suspicion or confirmed diagnosis of SCAR, all study medication must be discontinued.

Vaccinations in patients with immune-mediated inflammatory diseases.

Patients with immune-mediated inflammatory diseases (IMID) such as RA, IBD or psoriasis, are at increased risk of infection, partially because of the disease itself, but mostly because of treatment with immunomodulatory or immunosuppressive drugs. In spite of their elevated risk for vaccine-preventable disease, vaccination coverage in IMID patients is surprisingly low. This review summarizes current literature data on vaccine safety and efficacy in IMID patients treated with immunosuppressive or immunomodulatory drugs and formulates best-practice recommendations on vaccination in this population. Especially in the current era of biological therapies, including TNF-blocking agents, special consideration should be given to vaccination strategies in IMID patients. Clinical evidence indicates that immunization of IMID patients does not increase clinical or laboratory parameters of disease activity. Live vaccines are contraindicated in immunocompromized individuals, but non-live vaccines can safely be given. Although the reduced quality of the immune response in patients under immunotherapy may have a negative impact on vaccination efficacy in this population, adequate humoral response to vaccination in IMID patients has been demonstrated for hepatitis B, influenza and pneumococcal vaccination. Vaccination status is best checked and updated before the start of immunomodulatory therapy: live vaccines are not contraindicated at that time and inactivated vaccines elicit an optimal immune response in immunocompetent individuals.

A proposed EGFR inhibitor dermatologic adverse event-specific grading scale from the MASCC skin toxicity study group.

BACKGROUND: Accurate grading of dermatologic adverse events (AE) due to epidermal growth factor receptor (EGFR) inhibitors (EGFRIs) is necessary for drug toxicity determinations, interagent comparisons, and supportive care trials. The most widely used severity grading scale, the National Cancer Institute's Common Terminology Criteria for Adverse Events version 4.0 (NCI-CTCAE v4.0), was not designed specifically for this class of agents and may result in underreporting and poor grading of distinctive adverse events. We believe a class-specific grading scale is needed to help standardize assessment and improve reporting of EGFRI-associated dermatologic AEs. METHODS: The Multinational Association of Supportive Care in Cancer (MASCC) Skin Toxicity Study Group conducted an international multidisciplinary meeting that included 20 clinicians and researchers from academic centers and government agencies. Experts from different disciplines presented current information specific to EGFRI-induced dermatologic toxicities: grading scale development, pharmacovigilance safety reporting, health-related quality of life, patient reporting, and pharmacology. Group discussions, literature reviews, and professional expertise established the theoretical foundation for the proposed grading scale. RESULTS: A new grading system is proposed for the most common events associated with EGFRI-induced dermatologic AEs: papulopustular reaction or acneiform rash, nail changes, erythema, pruritus, xerosis, hair changes, telangiectasias, hyperpigmentation, mucositis, flushing, radiation dermatitis, hyposalivation, and taste changes. The proposed scale maintains consistency with the grading principles and language of the existing CTCAE version 4.0 and MedDRA terminology and includes relevant patient-reported health-related quality of life factors. CONCLUSIONS: A grading scale specific to EGFR inhibitor dermatologic AEs is presented for formal integration into future versions of CTCAE and for validation in clinical trial settings. The study group designed this scale to detect and report EGFRI-related toxicities with greater sensitivity, specificity, and range than the scales currently used. This scale should serve as a foundation for efforts to perform objective interdrug comparisons and assessments of supportive care treatment strategies more effectively than with current methods.