Long-Term Effectiveness of Dupilumab in Patients with Atopic Dermatitis: Results up to 3 Years from the RELIEVE-AD Study.

INTRODUCTION: Atopic dermatitis (AD) can require long-term therapy. Few real-world studies have evaluated long-term effectiveness from the patients' perspective. The aim of this study was to evaluate patient-reported outcomes (PROs) during long-term dupilumab treatment. METHODS: Adults with moderate-to-severe AD who initiated dupilumab through the US manufacturer patient support program and participated in RELIEVE-AD (a prospective patient survey study with a 12-month follow-up) were recontacted 30-36 months post-initiation regardless of current dupilumab use. The online questionnaire consisted of PROs, including the Atopic Dermatitis Control Tool (ADCT), use of concomitant AD therapies, satisfaction with current therapy, global change in itch relative to before dupilumab initiation, non-itch skin symptoms (skin pain/soreness, hot/burning feeling, and sensitivity to touch), flares, Dermatology Life Quality Index, sleep problems, and the AD-specific Work Productivity and Activity Impairment Questionnaire. RESULTS: Of 698 patients who initiated dupilumab (baseline) and were recontacted, 425 completed the 30-36-month survey. Significant reductions from baseline were reported in concomitant AD therapy use (P < 0.05); 54.4% reported not using other AD medications vs. 12.8% at baseline. At 30-36 months, all results (non-itch skin symptoms, flares, sleep problems, health-related quality of life work/activity impairment, disease control, and treatment satisfaction) were similar to or incrementally better than the 12-month timepoint, with significant improvements vs. baseline (P < 0.001). Global change in itch was reported as "very much better" by 75.3% of respondents. Adequate disease control (score < 7 on ADCT) was reported by 80.7% of respondents, and 86.8% were satisfied with the treatment. CONCLUSIONS: In clinical practice settings, patient-reported benefits of dupilumab were maintained in survey respondents during long-term treatment up to 36 months while the use of concomitant AD therapies reduced.

Atopic dermatitis (also known as eczema) is a chronic skin disease that can have a profoundly negative effect on patients' quality of life. To control disease symptoms, patients often need long-term treatment. Dupilumab is a treatment that has shown benefits in adults with moderate-to-severe atopic dermatitis (AD) when used in long-term (under 4 years) clinical trials; however, few studies have evaluated patients' experiences of long-term dupilumab treatment outside of a clinical trial setting. This study was conducted to do so: 425 adults with moderate-to-severe AD who received dupilumab through a US manufacturer patient support program filled in an online questionnaire 30­36 months after starting treatment. The questionnaire included items on use of additional AD therapies, AD symptoms, quality of life, disease control, and satisfaction with treatment. Patients' responses showed that, at 30­36 months after starting dupilumab treatment, 54% of patients reported not using any other medications for AD vs. 13% of patients when starting dupilumab treatment. In addition, since starting dupilumab, 75% of patients reported one of the most burdensome AD symptoms, itch, as being "very much better" vs. before starting treatment; 81% reported control of AD symptoms; 85% reported a meaningful improvement in quality of life; and 76% were "extremely" or "very" satisfied with the treatment. In summary, this study showed that long-term dupilumab treatment provides continued improvement in symptoms, treatment satisfaction, disease control, and quality of life in adults with moderate-to-severe AD while reducing the need for other AD treatments. Video abstract: How do patients with atopic dermatitis perceive long-term dupilumab treatment in the real world? (MP4 31888 kb).

No Increased Risk of Overall Infection in Adults with Moderate-to-Severe Atopic Dermatitis Treated for up to 4 Years with Dupilumab.

INTRODUCTION: Patients with atopic dermatitis (AD) have an increased risk for infections. This open-label extension study, LIBERTY AD OLE, reports the incidence of infections in adults with moderate-to-severe AD treated with dupilumab for up to 4 years. METHODS: We evaluated infections in adults with moderate-to-severe AD treated with dupilumab 300 mg weekly (qw) or every 2 weeks (q2w; approved regimen) for up to 4 years. Topical corticosteroids (TCS) and calcineurin inhibitors (TCI) were permitted. Exposure-adjusted incidence rates (number of patients with at least one event per 100 patient-years [nP/100 PY]) are reported. RESULTS: Overall, 2677 patients were enrolled and treated with dupilumab: 352 (13.1%) completed up to week 204; 226 patients (8.4%) switched from qw to q2w during the trial. Rates of overall infections (71.27 nP/100 PY), serious and/or severe infections (1.39 nP/100 PY), and infections leading to discontinuation (0.34 nP/100 PY) were consistent with a previous 3-year analysis of this study and low compared with 1-year results in adults with AD treated with placebo + TCS. The cumulative number of patients with treatment-emergent serious or severe infections, non-herpetic or herpetic infections, and total skin infections decreased year-over-year. Limitations included open-label study design with no placebo arm; decreasing sample size at later time points due to sponsor decision to close sites following regulatory approval; qw dosing differs from approved q2w dosing; and patients could use TCS/TCI throughout the study, which may have impacted infection rates. CONCLUSIONS: Continuous long-term dupilumab treatment in adults with moderate-to-severe AD is not associated with an increased risk of overall systemic or cutaneous infections. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01949311. Video Abstract INFOGRAPHIC.

Atopic dermatitis is a chronic disease that causes dry skin, skin inflammation, and itching. Patients with atopic dermatitis have an increased risk of bacterial or viral skin infections, which can cause further serious infections in the entire body. This study investigated the rates of infections in adults with moderate-to-severe atopic dermatitis after 204 weeks (almost 4 years) of dupilumab treatment. The patients received 300 mg of dupilumab every week, and a subset of patients switched to the approved dose of 300 mg of dupilumab every 2 weeks. Patients were allowed the use of topical corticosteroids. Among the patients receiving dupilumab for up to 4 years, rates of total infections, serious and severe infections, and infections leading to treatment discontinuation were consistent with a previously published 3-year evaluation. The infection rates in the 4-year study were lower than those in a previous 1-year study in adults with atopic dermatitis treated with placebo and topical corticosteroids. Importantly, our results showed that the cumulative number of patients with total skin infections decreased over 4 years of dupilumab treatment. The number of patients with severe infections appearing after the start of treatment, herpes viral infections, and infections not involving herpes virus also decreased yearly during the 4-year study. The safety data presented here show that long-term dupilumab treatment does not increase the overall risk of skin infections, and provides important evidence related to continuous use of dupilumab treatment in adults with moderate-to-severe atopic dermatitis.

Real-World Effectiveness of Dupilumab in Atopic Dermatitis Patients: Analysis of an Electronic Medical Records Dataset.

INTRODUCTION: While the efficacy of dupilumab for the treatment of adults with moderate-to-severe atopic dermatitis (AD) has been demonstrated in several clinical trials, patients in such trials may not necessarily reflect the real-world clinical practice setting. This study evaluated the real-world effectiveness of dupilumab in adults with moderate-to-severe AD based on physician global assessment, percent body surface area affected, and patient-reported itch. METHODS: From Modernizing Medicine's Electronic Medical Assistant dermatology-specific electronic medical records, adults (≥ 18 years) were identified with a diagnosis of AD and ≥ 1 dupilumab prescription (index event) between 1 April 2017 and 31 January 2019. Three cohorts were identified based on 3-month pre-index (1) Investigator Global Assessment (IGA) score ≥ 3, (2) an itch severity numerical rating scale (NRS) score ≥ 3, and (3) body surface area (BSA) affected ≥ 10%. Changes from pre-index on the outcome within each cohort were evaluated at 4 months post-index. Patients were also stratified for evaluation of outcomes by baseline demographic (sex, age) and prior AD treatments (topical therapy only or no treatment, any systemic therapy). RESULTS: More than 70% of the 435 AD patients with baseline IGA score ≥ 3 improved to an IGA score of ≤ 2 at month 4 post-dupilumab initiation, including 42.8% who achieved IGA 0/1 (clear/minimal). Among 112 patients with a pre-index itch severity NRS ≥ 3, scores were reduced from mean (SD) 7.0 (2.4) pre-index to 2.8 (2.8) at month 4 (p < 0.0001); 70.5% of patients had a reduction ≥ 3 points. In the BSA cohort (n = 387), affected BSA was significantly reduced from a pre-index mean (SD) of 39.3% (26.1%) to 16.3% (21.2%) at month 4 (p < 0.0001). Significant improvements in IGA, itch NRS, and BSA were observed regardless of demographic (age and sex) or clinical characteristics such as treatment history (all p < 0.0001 compared with pre-index). CONCLUSIONS: Consistent with outcomes observed in clinical trials, patients treated with dupilumab in real-world clinical settings achieved clinically meaningful improvements in severity and extent of AD and severity of itch comparable to those reported in clinical trials at a similar time point.

Treatment Outcomes Associated With Dupilumab Use in Patients With Atopic Dermatitis: 1-Year Results From the RELIEVE-AD Study.

IMPORTANCE: Clinical trial populations may not reflect clinical practice: knowledge generated in other settings can inform clinical decision-making. OBJECTIVE: To evaluate self-reported disease control and quality of life after initiating dupilumab treatment in patients with atopic dermatitis (AD) in the the clinical setting. DESIGN, SETTING, AND PARTICIPANTS: This cohort study using an online survey administered prior to (baseline) and at 1, 2, 3, 6, 9, and 12 months after dupilumab initiation included adults with moderate-to-severe AD who initiated treatment with dupilumab through the US patient support program and agreed to participate in the study. Data were collected between January 2018 and January 2020 and the analysis was completed in May 2020. INTERVENTIONS: Clinically driven treatment with dupilumab. MAIN OUTCOMES AND MEASURES: Disease control measured by the Atopic Dermatitis Control Tool (ADCT); concomitant AD therapies; satisfaction with therapy; skin symptoms (skin pain/soreness, hot/burning feeling, sensitivity to touch) assessed using numerical rating scales; flares; health-related quality of life assessed using the Dermatology Life Quality Index; sleep problems assessed using the ADCT item and a stand-alone question; and the AD-specific Work Productivity and Activity Impairment Questionnaire. RESULTS: Of 699 patients who initiated dupilumab (431 [61.7%] female, 515 [73.7%] White), 632 and 483 completed the survey at months 1 and 12, respectively. As-observed results showed that most patients achieved adequate disease control (ADCT total score) at month 1 with further improvement at month 12 (385 of 632 patients [60.9%] and 374 of 483 [77.4%] for the 2 time points, respectively, vs 41 of 699 [5.3%] at baseline; both P < .001). Use of other AD therapies was reduced at each follow-up vs baseline, including topical and systemic corticosteroids, which were reduced at month 12 to 40.4% (195 of 483 patients) and 6.2% (30 of 483 patients), respectively, from 68.1% (476 of 699) and 34.9% (244 of 699), respectively, at baseline (both P < .001 vs baseline). Patient satisfaction with AD treatment was higher than baseline (120 of 699 [17.7%]) at each follow-up to 85.1% (411 of 483) at month 12 (P < .001). At each follow-up, patients reported reductions in flares, itch, skin symptoms, and improved sleep, health-related quality of life, and daily activities vs baseline. Results were consistent based on observed data and imputed data using pattern mixture models for missing data. CONCLUSIONS AND RELEVANCE: Consistent with patient-reported outcomes in clinical trials, this cohort study found that dupilumab treatment was associated with rapid and sustained disease control for up to 12 months as demonstrated by statistically significant improvements relative to baseline on all patient-reported outcomes including treatment satisfaction.

Efficacy of Dupilumab in Atopic Dermatitis: The Patient's Perspective.

INTRODUCTION: Atopic dermatitis (AD), a predominantly type 2 inflammatory skin disease, affects approximately 2-5% of adults, with a high burden of disease. In moderate-to-severe AD, lesions can be extensive and pruritus intense with patients experiencing skin pain, sleep and mental health disturbances, and diminished quality of life (QoL). METHODS: The objective of this study was to evaluate the efficacy of dupilumab for the treatment of AD from the patients' perspective using patient-reported outcome data from four clinical trials (CHRONOS, SOLO 1&2, and CAFÉ) in patients (N = 1553) receiving either the approved 300 mg q2w dupilumab with/without topical corticosteroids (TCS) dose or control (placebo or placebo + TCS). Patient Global Assessment of Disease Status (PGADS) was used to measure patients' well-being and Patient Global Assessment of Treatment Effect (PGATE) was used to measure treatment efficacy. Patients were asked "Considering all the ways in which your eczema affects you, indicate how well you are doing" to assess their perception of well-being and "How would you rate the way your eczema responded to the study medication?" to assess their perception of treatment effect. Possible responses for both metrics included poor, fair, good, very good, and excellent. RESULTS: In all four studies, a significantly higher proportion of dupilumab-treated patients reported "Good"/"Very Good"/"Excellent" disease status from week 2 through study end versus control (CHRONOS, 52 weeks: 69.8% vs. 25.1%; SOLO 1&2, 16 weeks: 59.5% vs. 24.6%; CAFÉ, 16 weeks: 84.1% vs. 45.4%; all P < 0.0001), and significantly more dupilumab-treated patients reported "Good"/"Very Good"/"Excellent" treatment efficacy versus control (CHRONOS: 72.6% vs. 24.8%; SOLO 1&2: 65.0% vs. 21.1%; CAFÉ, 16 weeks: 85.0% vs. 36.1%; all P < 0.0001). CONCLUSION: Adult patients with AD perceived that dupilumab with/without concomitant TCS was highly efficacious and improved overall disease status and well-being as early as week 2 and throughout treatment periods up to 1 year. Video Abstract (MP4 90521 kb).

Dupilumab Demonstrates Rapid and Consistent Improvement in Extent and Signs of Atopic Dermatitis Across All Anatomical Regions in Pediatric Patients 6 Years of Age and Older.

INTRODUCTION: In phase III trials in adolescents and children with atopic dermatitis (AD), dupilumab significantly decreased global disease severity. However, the effects of dupilumab on the extent and signs of AD across different anatomical regions were not reported. Here we characterize the efficacy of dupilumab in improving the extent and signs of AD across four different anatomical regions in children and adolescents. METHODS: A post hoc subset analysis was performed using data from two randomized, double-blind, placebo-controlled, international multicenter, phase III trials of dupilumab therapy in adolescents aged ≥ 12 to < 18 years with moderate-to-severe AD and children aged ≥ 6 to < 12 years with severe AD. Endpoints included mean percentage change in Eczema Area and Severity Index (EASI) signs (erythema, edema/papulation, excoriation, lichenification) and extent of AD (measured by percentage of body surface area [% BSA] involvement) from baseline to week 16 across four anatomical regions (head and neck, trunk, upper extremities, lower extremities). RESULTS: Dupilumab improved both the extent and severity of AD signs across the four anatomical regions. Improvements were shown to be similar across the four anatomical regions for % BSA involvement and for reduction in EASI signs. Improvements in all signs were seen early, within the first 4 weeks of treatment, and were sustained through week 16, across all regions. CONCLUSIONS: In pediatric patients 6 years of age and older, treatment with dupilumab resulted in rapid and consistent improvement in the extent and signs of AD across all anatomical regions. CLINICALTRIALS. GOV IDENTIFIERS: LIBERTY AD ADOL (NCT03054428) and LIBERTY AD PEDS (NCT03345914). Does dupilumab provide improvement in atopic dermatitis across all anatomical regions in children and adolescents? (MP4 48,385 kb).

Real-world persistence with dupilumab among adults with atopic dermatitis.

BACKGROUND: The real-world persistence with dupilumab therapy for atopic dermatitis (AD) is unknown. OBJECTIVE: To characterize adults with AD who initiated dupilumab and evaluate persistence with dupilumab therapy. METHODS: This retrospective cohort study used the IBM MarketScan Commercial and Medicare database. Adults with AD who initiated dupilumab (first dispensation = index date) between March 28, 2017, and March 31, 2018, were identified and followed up until September 30, 2018, or disenrollment. Twelve months of continuous preindex enrollment were required to characterize baseline treatment history and comorbidities. Kaplan-Meier analysis was used to estimate dupilumab persistence at 6 and 12 months, assuming a 14-day injection frequency and a 30-day grace period. RESULTS: A total of 1963 adults were identified who initiated dupilumab (mean [SD] age 42.1 [15.7] years; 50.7% women; 49.8% with ≥1 atopic comorbidity). Baseline AD treatments included topical corticosteroids (81.6%), systemic corticosteroids (72.5%), and systemic immunosuppressants (22.8%). Dupilumab persistence (95% confidence interval) at 6 and 12 months was 91.9% (90.7%-93.2%) and 77.3% (75.0%-79.7%), respectively. Among 329 patients who discontinued dupilumab, the risk of reinitiation was 78.8% (95% confidence interval: 75.8%-81.7%) within an average of 4 months. CONCLUSION: Dupilumab persistence at 12 months was high, suggesting patient satisfaction with effectiveness, tolerability, and treatment regimen.

Patient-Reported Ocular Disorders and Symptoms in Adults with Moderate-to-Severe Atopic Dermatitis: Screening and Baseline Survey Data from a Clinical Trial.

INTRODUCTION: Patients with atopic dermatitis (AD) have a greater risk of conjunctivitis and other ocular surface disorders than the general population. We evaluated the burden of ocular surface disorders and related symptoms prior to treatment initiation in adults with moderate-to-severe AD. METHODS: Patients were enrolled in a randomized, placebo-controlled, double-blinded, phase 3 trial of dupilumab administered with concomitant topical corticosteroids. At the beginning of the screening period, all enrolled patients completed a survey of ocular disorder diagnoses received in the past year; at baseline, patients completed a survey of frequency and severity of ocular symptoms (discomfort, itching, redness, and tearing) experienced in the past month. RESULTS: A total of 712 of 740 patients enrolled in the trial provided responses to the survey. At screening, 286 of 740 patients (38.6%) reported having at least one ocular disorder in the past year. At baseline, 499 of 712 respondents (70.1%) reported having at least one symptom within the past month. Of these patients, 4.4%, 6.0%, 5.5%, and 4.4%, respectively, reported having discomfort, itching, redness, and tearing all of the time. Mild discomfort, itching, redness, and tearing were reported by 26.1%, 33.7%, 30.8%, and 31.6% of patients, respectively, while 7.3%, 7.7%, 6.2%, and 4.2%, reported severe discomfort, itching, redness, and tearing, respectively. CONCLUSIONS: These data demonstrate a high burden of ocular surface disorders and related symptoms in a population of adults with moderate-to-severe AD. Dermatologists should be aware of increased incidence of these disorders in AD and query their patients for signs and symptoms of eye disease. CLINICALTRIALS. GOV REGISTRATION NUMBER: NCT02260986.

Topical Agents for the Treatment of Atopic Dermatitis

Approval of the new topical phosphodiesterase 4 inhibitor crisaborole ointment, 2%, to treat mild-to-moderate atopic dermatitis (AD) warrants careful consideration of available efficacy and safety data for topical therapies to contribute to a better understanding of the role of crisaborole in the treatment of mild-to-moderate AD. A literature review was conducted to identify results of randomized, blinded, vehicle-controlled trials of topical agents for the treatment of AD published from January 1, 1997 to April 30, 2018. This review summarizes the efficacy and safety data of topical therapies including corticosteroids, calcineurin inhibitors, and crisaborole and it shows that comparison among available agents is difficult because of differing methodologies used across clinical trials and that there is considerable variability in safety reporting among AD trials. Published clinical studies for crisaborole demonstrate its efficacy and manageable safety profile. J Drugs Dermatol. 2020;19(1):50-64. doi:10.36849/JDD.2020.4508

The Challenge of Managing Atopic Dermatitis in the United States.

BACKGROUND: Atopic dermatitis is a chronic inflammatory skin disease that affects up to 13% of children and 10% of adults in the United States. Among patients and their families, atopic dermatitis has a considerable effect on quality of life and represents a substantial economic burden. OBJECTIVE: To describe the impact and challenges of atopic dermatitis and to provide nondermatologists in the healthcare community an enhanced understanding of atopic dermatitis to facilitate treatment and pharmacy benefit discussions. DISCUSSION: Atopic dermatitis is a heterogeneous disease, and its diagnosis is hampered by a lack of objective diagnostic criteria. The current management guidelines address the distinct clinical phenotypes as a single disease and do not incorporate recent clinical advances, such as the targeting of specific inflammatory processes. The treatment guidelines for atopic dermatitis are complex and challenge healthcare providers, patients, and caregivers. Novel treatments can provide additional therapeutic options for patients with atopic dermatitis. CONCLUSIONS: Treatment options for atopic dermatitis are expanding with the development of novel anti-inflammatory therapies. An increased understanding of these advancements is necessary to optimize care for patients with atopic dermatitis.

Tolerability of Topical Treatments for Atopic Dermatitis.

Atopic dermatitis (AD) is a common inflammatory skin disease that is accompanied by increased sensitivity to itch-provoking and pain-provoking stimuli. Patients with AD experience skin pain before initiation of therapy and have also reported painful application site reactions in clinical trials of emollients and prescription topical therapies, including topical corticosteroids (TCSs), topical calcineurin inhibitors (TCIs), and a topical phosphodiesterase 4 (PDE4) inhibitor. To compare the sensory tolerability of prescription topical therapies for AD, a comprehensive literature search and analysis of published clinical trials was conducted. Sensory tolerability issues such as application site pain, burning, stinging, and pruritus were often among the most common adverse events or treatment-related adverse events in clinical trials for prescription topical therapies. Tolerability issues occurred at highest rates in trials of TCIs, followed by trials of the PDE4 inhibitor crisaborole and TCSs, although direct comparisons are not possible because of differences in study design. Tolerability issues in these clinical trials were generally mild to moderate and transient. This article also reviews published strategies for managing sensory tolerability issues in AD patients during treatment with topical therapies.Funding: Pfizer Inc., New York, NY.

The Challenge of Managing Psoriasis: Unmet Medical Needs and Stakeholder Perspectives.

BACKGROUND: Psoriasis is a debilitating chronic inflammatory autoimmune disease affecting approximately 7.4 million adults in the United States. Plaque psoriasis is the most common form, affecting 80% to 90% of patients. OBJECTIVES: To describe the impact and challenges that psoriasis presents for various stakeholders, and to provide nondermatologist healthcare decision makers with information to enhance their contributions to drug and pharmacy benefit design discussions. DISCUSSION: Psoriasis carries an increased risk for early mortality and an increased prevalence of comorbidities, including psoriatic arthritis, cardiovascular disease, and diabetes. It is also associated with anxiety, depression, and social isolation, and can negatively impact patients' relationships, productivity, and careers. The physical, psychologic, social, and economic impact of psoriasis, plus the associated stigma, result in cumulative impairment over a patient's lifetime. The current treatments for moderate-to-severe psoriasis include topical therapy, phototherapy, and systemic drugs (nonbiologic and biologic); however, patient satisfaction remains low, combination therapy and treatment switching are common, and many patients remain untreated or undertreated. Clinicians should consider the patient holistically, and should select treatment based on a range of factors, including disease severity (with physical and psychosocial manifestations), susceptibility to cumulative life-course impairment (considering personality, behavior, and cognition), comorbidities, concomitant medication, and patient preference. It is estimated that the total annual direct cost of treating psoriasis in the United States in 2015 exceeded $12.2 billion. CONCLUSION: Psoriasis is a complex disease, and appropriate management is correspondingly complex. Newer psoriasis treatments provide improved efficacy and safety versus traditional treatments, but challenges remain in ensuring patients access to these medications. An improved understanding of the barriers to appropriate treatment is needed, as well as clear and accessible information for payers and clinicians on current treatment options, to ensure that decision makers can control costs while providing patients with optimal care.

Long-term evaluation of analytical methods used in sirolimus therapeutic drug monitoring.

Results of therapeutic monitoring of sirolimus blood concentrations are assay and laboratory dependent. This study compared performance over time of the IMx microparticle enzyme immunoassay (MEIA), Architect chemiluminescent microparticle immunoassay (CMIA), and liquid chromatography with mass spectrometric detection (LC/MS/MS) as part of a proficiency testing scheme. Pooled samples from sirolimus-treated patients and whole-blood samples spiked with known quantities of sirolimus were assayed monthly between 2004 and 2012. When results of pooled patient samples were compared with LC/MS/MS, the MEIA assay showed an overall mean percent bias of -2.3% ± 11.2% that, although initially positive, became increasingly negative from 2007 through 2009. The CMIA, which replaced the MEIA assay, had a mean percent bias of 21.9% ± 12.3%, remaining stable from 2007 through 2012. Similarly, for spiked samples, the MEIA showed an increasingly negative bias over time vs. LC/MS/MS, whereas CMIA maintained a stable positive bias. Based on comparison of immunoassay measurements on individual patient samples, CMIA values were more than 25% higher than MEIA values. These results highlight the importance of continued proficiency testing and regular monitoring of sirolimus assay performance. Clinicians must be aware of the methodology used and adjust target levels accordingly to avoid potential effects on efficacy and toxicity.

Safety and success of kidney transplantation and concomitant immunosuppression in HIV-positive patients.

BACKGROUND: Human immunodeficiency virus-associated nephropathy (HIVAN) has become the third leading cause of end-stage renal disease (ESRD) in African Americans, and is expected to grow exponentially. Highly active antiretroviral therapy (HAART) has significantly prolonged the survival of patients with HIV infection. Despite the growing number of HIV-positive dialysis patients with prolonged life expectancy, kidney transplantation with immunosuppression has been declined because it is considered a waste of scarce donor kidneys due to potential increases in morbidity and mortality. METHODS: The institutional review board of Drexel University College of Medicine and Hahnemann University Hospital approved this prospective study. The aim was to find out safety and success of kidney transplantation, and the effect of immunosuppression on HIV infection. Forty HIV-positive dialysis patients received kidney transplantation between February 2001 and January 2004. Patient inclusion criteria were maintenance of HAART, plasma HIV-1 RNA of <400 copies/mL, absolute CD4 counts of 200 cells/muL or more. Immunosuppression was basiliximab induction and maintenance with cyclosporine, sirolimus, and steroids. HAART was continued post-transplant. Acute rejections were diagnosed by biopsy and treated with methylprednisolone. Surveillance biopsies were completed at 1, 6, 12, and 24 months, and evaluated for subclinical acute rejection, chronic allograft nephropathy, and HIVAN. RESULTS: One- and 2-year actuarial patient survival was 85% and 82%, respectively, and graft survival was 75% and 71%, respectively. Plasma HIV-1 RNA remained undetectable, and CD4 counts remained in excess of 400 cells per muL with no evidence of AIDS for up to 2 years. CONCLUSION: One- and 2-year graft survival is comparable to other high-risk populations receiving kidney transplantation. One- and 2-year patient survival is higher than HIV patients maintained on dialysis. Immunosuppression does not adversely affect HIV recipients maintained on HAART in the short term.

Steroid avoidance in renal transplantation using basiliximab induction, cyclosporine-based immunosuppression and protocol biopsies.

BACKGROUND: Reducing chronic steroid exposure is important to minimize steroid-related morbidity, particularly for susceptible renal transplant recipients. Steroid-free and steroid-sparing protocols have shown benefits, but safety has not been established for all populations. We investigated the safety of steroid avoidance (SA) in a population including African-Americans, using modern immunosuppression with protocol biopsy monitoring. METHODS: A randomized-controlled SA trial (early discontinuation, days 2-7) was conducted in a population (n = 77) including African-Americans and cadaveric kidney recipients. Patients received basiliximab, cyclosporine (CsA), and mycophenolate mofetil (MMF). In controls, steroids were tapered to 5 mg prednisone/d by day 30. Protocol biopsies were performed (1, 6, 12 and 24 months) to evaluate subclinical acute rejection (SCAR) and chronic allograft nephropathy (CAN). RESULTS: The SA did not result in significantly higher incidences of graft loss, AR, SCAR, CAN, or renal fibrosis. SA patients experienced similar renal function, comparable serum lipid levels, and a trend toward fewer cases of new-onset diabetes. Clinical outcomes of African-American and non-African-American patients did not significantly differ. CONCLUSIONS: The SA is safe in the context of basiliximab induction and CsA-based immunosuppression. This protocol could minimize steroid-related side effects in susceptible groups, including African-Americans, without increasing the risk of AR or graft failure.

Induction immunosuppression in kidney transplant recipients older than 60 years of age : safety and efficacy of ATGAM, OKT3 and Simulect.

BACKGROUND: The choice of induction immunosuppression for kidney transplantation in elderly recipients is dictated by the consideration of the risk of infection as well as efficacy in the prevention of acute rejection, thus allowing a reduction in subsequent maintenance immunosuppression and its attendant long-term adverse effects. OBJECTIVE: To compare the efficacy and safety of the antibody induction immunosuppression strategies in elderly recipients of kidney transplants. PATIENTS AND METHODS: We present retrospective data analysis on 183 kidney transplant recipients > or = 60 years of age at Hahnemann University Hospital (Philadelphia, PA, USA) over a 12-year period. We compared four consecutive cohorts of kidney transplant recipients receiving lymphocyte immune globulin, equine antithymocyte globulin (ATGAM) [n = 29]; muromonab CD3 (OKT3) [n = 45]; basiliximab (Simulect) with corticosteroid maintenance [n = 40]; and Simulect without corticosteroid maintenance (n = 69). RESULTS: Delayed graft function (DGF) was observed in 48% of patients receiving ATGAM, 35.6% in the OKT3 group and 35% in the Simulect group with corticosteroid maintenance and 36.2% in the Simulect group without corticosteroid maintenance. The rejection rate within the first 3 months was 31% in the ATGAM and OKT3 groups, 17.5% in the Simulect group with corticosteroid maintenance and 14.5% in the Simulect group without corticosteroid maintenance. These differences for DGF and acute rejection were statistically significant between patients receiving ATGAM and OKT3, ATGAM or OKT3 and both groups of Simulect (all p < 0.05). Patients receiving Simulect were free of adverse effects typically encountered by patients receiving polyclonal and monoclonal antibodies for induction. Patients receiving Simulect had much shorter hospital stays and benefited from significant reduction of costs compared with other groups. CONCLUSION: Our data indicate that kidney transplant recipients > or = 60 years of age benefit from induction therapy with Simulect followed by corticosteroid-free maintenance immunosuppression.