RESUMEN
Background: Treatment with baricitinib in combination with topical corticosteroids previously showed greater improvements in itch and sleep versus placebo in adults with moderate-to-severe AD. Objectives: To assess whether improvements in itch and sleep translate to greater quality of life (QoL), productivity and treatment benefit in AD. Materials & Methods: In this post hoc analysis with data from BREEZE-AD7 (NCT03733301), itch and sleep improvements at Week 16 were defined by ≥4-point improvements in the Itch Numeric Rating Scale and ≥1.5 decreases in the number of night-time awakenings since baseline, respectively. Dermatology Life Quality Index, Work Productivity and Activity Impairment-AD and Patient Benefit Index (PBI) scores were compared in patients with and without improvements. Proportions were analysed using logistic regression with non-responder imputation. Changes from baseline were calculated using ANCOVA, with last observation carried forward. Least square mean PBI scores were assessed using ANOVA. Results: More patients with itch improvement versus no itch improvement reported no impact of AD on QoL (28.4% vs. 6.0%). Daily activity impairment was lower in patients with itch improvement (-39.6% vs. -15.6%). A greater proportion of patients with sleep improvement versus no sleep improvement had no AD-related impact on QoL (24.1% vs. 1.5%). Patients with sleep improvement had less daily activity impairment (-35.0% vs. -18.5%). Patients with itch and sleep improvements experienced greater treatment benefit. Conclusion: Patients with AD who experienced clinically meaningful improvements in itch and sleep following treatment had significantly better QoL, productivity and treatment benefit. Addressing these symptoms is important to achieving meaningful and patient-relevant improvements in well-being.
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Dermatitis Atópica , Fármacos Dermatológicos , Corticoesteroides/uso terapéutico , Adulto , Azetidinas , Dermatitis Atópica/complicaciones , Dermatitis Atópica/diagnóstico , Dermatitis Atópica/tratamiento farmacológico , Fármacos Dermatológicos/uso terapéutico , Método Doble Ciego , Humanos , Prurito/diagnóstico , Prurito/tratamiento farmacológico , Prurito/etiología , Purinas , Pirazoles , Calidad de Vida , Índice de Severidad de la Enfermedad , Sulfonamidas , Resultado del TratamientoRESUMEN
BACKGROUND: Baricitinib, an oral selective Janus kinase (JAK)1 and JAK 2 inhibitor, was shown to improve the signs and symptoms of moderate-to-severe atopic dermatitis (AD). OBJECTIVES: To evaluate the efficacy and safety of baricitinib with background topical corticosteroids (TCS) in patients with moderate-to-severe AD and inadequate response, intolerance or contraindication to ciclosporin A (CA). METHODS: In this double-blind, randomized, placebo-controlled, phase III study, patients were randomized 1: 1: 2: 1 to placebo (N = 93), baricitinib 1 mg (N = 93), 2 mg (N = 185) or 4 mg (N = 92) with background TCS. The primary endpoint was the proportion of patients receiving baricitinib 4 mg or 2 mg (+ TCS) vs. placebo + TCS who achieved ≥ 75% improvement from baseline in the Eczema Area and Severity Index (EASI 75) at week 16. RESULTS: Baricitinib 4 mg + TCS was superior to placebo + TCS for EASI 75 (4 mg: 32%, placebo: 17%, P = 0·031) at week 16 and for improvements in itch, skin pain and number of night-time awakenings owing to itch. Improvements were maintained through 52 weeks of treatment. Treatment-emergent adverse events (TEAEs) were more common with baricitinib than placebo (+ TCS); most were mild or moderate. The most frequent TEAEs with baricitinib 4 mg + TCS were nasopharyngitis, herpes simplex, influenza and headache. No deaths or deep vein thromboses were reported. CONCLUSIONS: Baricitinib 4 mg + TCS improved the signs and symptoms of moderate-to-severe AD through 52 weeks of treatment in patients with inadequate response, intolerance or contraindication to CA. The safety profile was consistent with previous studies of baricitinib in moderate-to-severe AD. What is already known about this topic? Ciclosporin A is indicated for the treatment of atopic dermatitis that is refractory to topical therapies. However, its use is limited by safety concerns and it may not provide adequate response for some patients. Baricitinib, an oral selective Janus kinase (JAK)1 and JAK2 inhibitor, has been shown to improve the signs and symptoms of moderate-to-severe atopic dermatitis as a monotherapy or in combination with topical corticosteroids. What does this study add? Baricitinib combined with background low- or moderate-potency topical corticosteroids provided improvements in the signs and symptoms of moderate-to-severe atopic dermatitis through 1 year of treatment in patients with a contraindication, intolerance or failure to respond to ciclosporin A. The most common treatment-emergent adverse events with baricitinib 4 mg were nasopharyngitis, herpes simplex, influenza and headache. The safety profile was consistent with previous studies in patients with moderate-to-severe atopic dermatitis.
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Dermatitis Atópica , Fármacos Dermatológicos , Herpes Simple , Gripe Humana , Nasofaringitis , Corticoesteroides , Azetidinas , Contraindicaciones , Ciclosporina/uso terapéutico , Dermatitis Atópica/diagnóstico , Dermatitis Atópica/tratamiento farmacológico , Fármacos Dermatológicos/uso terapéutico , Método Doble Ciego , Cefalea/inducido químicamente , Herpes Simple/tratamiento farmacológico , Humanos , Gripe Humana/inducido químicamente , Gripe Humana/tratamiento farmacológico , Nasofaringitis/inducido químicamente , Purinas , Pirazoles , Índice de Severidad de la Enfermedad , Sulfonamidas , Resultado del TratamientoRESUMEN
BACKGROUND: The validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD™) is a standardized severity assessment for use in clinical trials and registries for atopic dermatitis (AD). OBJECTIVES: To investigate the reliability, validity, responsiveness and within-patient meaningful change of the vIGA-AD. METHODS: Data were analysed from adult patients with moderate-to-severe AD in the BREEZE-AD1 (N = 624 patients; NCT03334396), BREEZE-AD2 (N = 615; NCT03334422) and BREEZE-AD5 (N = 440; NCT03435081) phase III baricitinib clinical studies. RESULTS: Across studies, test-retest reliability for stable patients showed moderate-to-good agreement [range of Kappa values for Patient Global Impression of Severity-Atopic Dermatitis (PGI-S-AD), 0·516-0·639; for Eczema Area and Severity Index (EASI), 0·658-0·778]. Moderate-to-large correlations between vIGA-AD and EASI or body surface area (range at baseline, 0·497-0·736; Week 16, 0·716-0·893) supported convergent validity. Known-groups validity was demonstrated vs. EASI and PGI-S-AD (vIGA-AD for severe vs. moderate EASI categories at baseline, P < 0·001). Responsiveness was demonstrated vs. EASI (P < 0·001 for much improved vs. improved and improved vs. stable). Anchor- and distribution-based methods supported a vIGA-AD change of -1·0 as clinically meaningful. These findings are limited to populations defined by the studies' inclusion and exclusion criteria. CONCLUSIONS: The vIGA-AD demonstrated sufficient reliability, validity, responsiveness and interpretation standards for use in clinical trials. What is already known about this topic? A description of the development of the validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD™) has been published previously. What does this study add? The current study validates the vIGA-AD by demonstrating appropriate test-retest reliability, convergent validity, known-groups validity and responsiveness across three baricitinib clinical studies. In addition, a 1-point change was identified as a clinically meaningful patient-perceived change minimal clinically important difference in the vIGA-AD. What are the clinical implications of the work? The vIGA-AD is a measure for investigator assessment of atopic dermatitis suitable for use in clinical research.
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Dermatitis Atópica , Adulto , Azetidinas , Ensayos Clínicos Fase III como Asunto , Dermatitis Atópica/diagnóstico , Dermatitis Atópica/tratamiento farmacológico , Humanos , Evaluación de Resultado en la Atención de Salud , Purinas , Pirazoles , Reproducibilidad de los Resultados , Índice de Severidad de la Enfermedad , SulfonamidasRESUMEN
BACKGROUND: Alopecia areata is an autoimmune condition characterized by rapid hair loss in the scalp, eyebrows, and eyelashes, for which treatments are limited. Baricitinib, an oral, selective, reversible inhibitor of Janus kinases 1 and 2, may interrupt cytokine signaling implicated in the pathogenesis of alopecia areata. METHODS: We conducted two randomized, placebo-controlled, phase 3 trials (BRAVE-AA1 and BRAVE-AA2) involving adults with severe alopecia areata with a Severity of Alopecia Tool (SALT) score of 50 or higher (range, 0 [no scalp hair loss] to 100 [complete scalp hair loss]). Patients were randomly assigned in a 3:2:2 ratio to receive once-daily baricitinib at a dose of 4 mg, baricitinib at a dose of 2 mg, or placebo. The primary outcome was a SALT score of 20 or less at week 36. RESULTS: We enrolled 654 patients in the BRAVE-AA1 trial and 546 in the BRAVE-AA2 trial. The estimated percentage of patients with a SALT score of 20 or less at week 36 was 38.8% with 4-mg baricitinib, 22.8% with 2-mg baricitinib, and 6.2% with placebo in BRAVE-AA1 and 35.9%, 19.4%, and 3.3%, respectively, in BRAVE-AA2. In BRAVE-AA1, the difference between 4-mg baricitinib and placebo was 32.6 percentage points (95% confidence interval [CI], 25.6 to 39.5), and the difference between 2-mg baricitinib and placebo was 16.6 percentage points (95% CI, 9.5 to 23.8) (P<0.001 for each dose vs. placebo). In BRAVE-AA2, the corresponding values were 32.6 percentage points (95% CI, 25.6 to 39.6) and 16.1 percentage points (95% CI, 9.1 to 23.2) (P<0.001 for each dose vs. placebo). Secondary outcomes for baricitinib at a dose of 4 mg but not at a dose of 2 mg generally favored baricitinib over placebo. Acne, elevated levels of creatine kinase, and increased levels of low- and high-density lipoprotein cholesterol were more common with baricitinib than with placebo. CONCLUSIONS: In two phase 3 trials involving patients with severe alopecia areata, oral baricitinib was superior to placebo with respect to hair regrowth at 36 weeks. Longer trials are required to assess the efficacy and safety of baricitinib for alopecia areata. (Funded by Eli Lilly under license from Incyte; BRAVE-AA1 and BRAVE-AA2 ClinicalTrials.gov numbers, NCT03570749 and NCT03899259.).
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Alopecia Areata , Inhibidores de las Cinasas Janus , Adulto , Alopecia Areata/tratamiento farmacológico , Azetidinas/efectos adversos , Azetidinas/uso terapéutico , Humanos , Inhibidores de las Cinasas Janus/efectos adversos , Inhibidores de las Cinasas Janus/uso terapéutico , Purinas/efectos adversos , Purinas/uso terapéutico , Pirazoles/efectos adversos , Pirazoles/uso terapéutico , Sulfonamidas/efectos adversos , Sulfonamidas/uso terapéuticoRESUMEN
BACKGROUND: Skin pain (discomfort/soreness) is a common symptom associated with atopic dermatitis (AD). OBJECTIVE: To evaluate rapid changes in skin pain severity with baricitinib, and its impact on patient quality of life (QoL) in adults with moderate-to-severe AD who were inadequate responders to topical therapy. METHODS: Adult patients with moderate-to-severe AD who were inadequate responders to topical therapies (N = 440, BREEZE-AD5 [NCT03435081]) were randomized to once-daily placebo, baricitinib 1 mg, or baricitinib 2 mg for 16 weeks. Change in Skin Pain Numeric Rating Scale (NRS) scores were assessed for the randomized population. Skin Pain NRS and Dermatology Life Quality Index (DLQI) scores were assessed for Skin Pain Response groups and patients with Body Surface Area (BSA) 10% to 50%. RESULTS: Skin Pain NRS improvement was significant versus placebo by day 1 baricitinib 2 mg (least squares mean [LSM] difference -4.4%, P = .048) and by day 2 for baricitinib 1 mg (-6.7%, P = .011). As measured weekly, improvement was significant starting at Week 1 and remained significant through Week 16 for both doses. At Week 16, 70.9% of Skin Pain NRS responders vs 10.4% of nonresponders had a clinically meaningful improvement in DLQI (P < .0001). At week 16, LSM DLQI change from baseline was -11.1 for all Skin Pain NRS responders versus -3.5 for nonresponders (P < .0001). Patients with BSA 10% to 50% showed similar trends. CONCLUSIONS: Patients with moderate-to-severe AD, treated with baricitinib, reported rapid improvements in skin pain severity by day 1 for baricitinib 2 mg and day 2 for baricitinib 1 mg and remained effective through 16 weeks of treatment, which positively impacted patient QoL.
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Dermatitis Atópica , Adulto , Anticuerpos Monoclonales Humanizados/uso terapéutico , Azetidinas , Dermatitis Atópica/complicaciones , Dermatitis Atópica/diagnóstico , Dermatitis Atópica/tratamiento farmacológico , Método Doble Ciego , Humanos , Dolor/tratamiento farmacológico , Dolor/etiología , Dimensión del Dolor , Purinas , Pirazoles , Calidad de Vida , Índice de Severidad de la Enfermedad , Sulfonamidas , Resultado del TratamientoRESUMEN
PURPOSE: Alopecia areata (AA) is a common disorder of patchy hair loss which carries a substantial psychological burden for patients. The current understanding of AA prevalence, disease course and burden is limited, and further research is needed to improve patient care. This prospective cohort of AA patients within the Danish Skin Cohort was established to provide data that can serve as a tool in future studies of for example, AA epidemiology and disease burden. PARTICIPANTS: A total of 1494 patients with dermatologist-verified AA were included in the cohort. Patients were invited and included through electronic or phone-based questionnaires. Information regarding demographics, biometrics, lifestyle factors, skin type, AA onset and development, health-related quality of life and self-reported severity assessment was collected. FINDINGS TO DATE: The mean (SD) age of AA onset was 32.7 (17.6) years. The mean body mass index and history of cigarette smoking was comparable with the general population. The majority (92.5%) of participants were Caucasian. In total, 72.4% of patients received their diagnosis by a physician within a year after onset of symptoms, and 66.9% reported to still have symptoms of AA within the past year. A total of 12% reported to have a first-degree family member with AA. In total, 31.4% of patients were missing all or nearly all hairs on their scalp, 32.2% had no or barely no eyelashes and 36.2% had no or barely no eyebrow hairs. Overall, most patients (55.7%) did not experience irritated eyes, but 30% reported slight eye irritation and 47.2% reported no damage to finger nails or toenails. FUTURE PLANS: Observational studies regarding comorbidities, psychosocial burden of AA and efficacy of pharmacological interventions will be carried out and additional data will be linked from nationwide registries of routinely collected data. Furthermore, follow-up survey data will be added for longitudinal analyses.
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Alopecia Areata , Adulto , Alopecia Areata/epidemiología , Costo de Enfermedad , Dinamarca/epidemiología , Humanos , Estudios Prospectivos , Calidad de VidaRESUMEN
BACKGROUND: Baricitinib previously demonstrated improvements in itch and sleep disturbance versus placebo in adults with moderate-to-severe atopic dermatitis (AD). OBJECTIVES: Examine if itch and sleep improvements are associated with better quality of life (QoL) and productivity in patients with AD. METHODS: Data were drawn from BREEZE-AD5 (NCT03435081). Itch and sleep improvement at Week 16 were defined using ≥4-point improvements in the Itch Numeric Rating Scale and ≥1.5 decreases in the number of nighttime awakenings since baseline, respectively. Patients with and without improvements were compared on Dermatology Life Quality Index (DLQI) and Work Productivity and Activity Impairment-AD scores. Changes from baseline were analyzed using ANCOVA with last observation carried forward. Proportions were analyzed using logistic regression with non-responder imputation. RESULTS: Greater proportions of patients with versus without itch improvement indicated no impact of AD on QoL (37.7 vs. 1.8%). Patients with itch improvement had greater decreases in work time impaired (-29.3 vs. -5.6%). More patients with versus without sleep improvement reported no effect of AD on QoL (25.5 vs. 1.1%); patients with better sleep experienced larger reductions in work time spent impaired (-33.3 vs. -6.1%). CONCLUSIONS: Patients with AD who experienced itch and sleep improvement had significantly better QoL and productivity.
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Dermatitis Atópica , Calidad de Vida , Adulto , Azetidinas , Dermatitis Atópica/complicaciones , Dermatitis Atópica/tratamiento farmacológico , Humanos , Medición de Resultados Informados por el Paciente , Prurito/tratamiento farmacológico , Prurito/etiología , Purinas , Pirazoles , Índice de Severidad de la Enfermedad , Sueño , SulfonamidasRESUMEN
BACKGROUND: The current classification for alopecia areata (AA) does not provide a consistent assessment of disease severity. OBJECTIVE: To develop an AA severity scale based on expert experience. METHODS: A modified Delphi process was utilized. An advisory group of 22 AA clinical experts from the United States was formed to develop this AA scale. Representatives from the pharmaceutical industry provided feedback during its development. RESULTS: Survey responses were used to draft severity criteria, aspiring to develop a simple scale that may be easily applied in clinical practice. A consensus vote was held to determine the final AA severity statement, with all AA experts agreeing to adopt the proposed scale. LIMITATIONS: The scale is a static assessment intended to be used in clinical practice and not clinical trials. CONCLUSION: The final AA disease severity scale, anchored in the extent of hair loss, captures key features commonly used by AA experts in clinical practice. This scale will better aid clinicians in appropriately assessing severity in patients with this common disease.
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Alopecia Areata , Alopecia , Alopecia Areata/diagnóstico , Alopecia Areata/tratamiento farmacológico , Consenso , Humanos , Índice de Severidad de la EnfermedadRESUMEN
INTRODUCTION: Skin pain (described as discomfort or soreness) is increasingly recognized as a symptom of atopic dermatitis which impacts patient quality of life. This analysis examined the effect of baricitinib on skin pain in atopic dermatitis in three phase 3 studies (BREEZE-AD1, -AD2, and -AD7). METHODS: Patients were randomly assigned 2:1:1:1 to receive once-daily placebo, baricitinib 1 mg, 2 mg, or 4 mg in BREEZE-AD1 (N = 624) and -AD2 (N = 615) and 1:1:1 to receive once-daily placebo, baricitinib 2 mg, or 4 mg, with topical corticosteroids, in BREEZE-AD7 (N = 329) for 16 weeks. Patients recorded their skin pain severity using the Skin Pain Numerical Rating Scale (NRS) via an electronic daily diary. Data were analyzed by study as least squares mean change from baseline in daily scores for the randomly assigned patients using mixed model repeated measures analysis. Analysis of Skin Pain NRS response was done using logistic regression using non-responder imputation. RESULTS: Baricitinib produced significant percentage change from baseline compared with placebo in patient-reported skin pain severity by day 2 in BREEZE-AD1 (baricitinib 4 mg - 11.9%, p < 0.001; baricitinib 2 mg - 6.4%, p = 0.016; baricitinib 1 mg - 6.2%, p = 0.016), -AD2 (baricitinib 4 mg - 12.6%, p < 0.001; baricitinib 2 mg - 5.6%, p = 0.036; baricitinib 1 mg - 6.9%, p = 0.011), and -AD7 (baricitinib 4 mg - 6.9%, p = 0.04; baricitinib 2 mg - 7.9%, p = 0.018). A greater proportion of patients treated with baricitinib reported at least a 4-point reduction in Skin Pain NRS score at week 16 (Skin Pain NRS responders) in BREEZE-AD1 (baricitinib 4 mg 25.3%, p < 0.001), -AD2 (baricitinib 4 mg 20.0%, p < 0.001; baricitinib 2 mg 19.0%, p < 0.001), and -AD7 (baricitinib 4 mg 48.8%, p < 0.001; baricitinib 2 mg 45.2%, p = 0.004) compared to placebo. A significantly higher proportion of Skin Pain NRS responders also achieved at least a 4-point improvement in Dermatology Life Quality Index at week 16 when compared with Skin Pain NRS non-responders in BREEZE-AD1 (89.2%, p < 0.0001), -AD2 (92.5%, p < 0.0001), and -AD7 (88.3%, p < 0.0001). CONCLUSION: Baricitinib improved patient-reported skin pain severity as early as day 2. CLINICALTRIALS. GOV IDENTIFIERS: BREEZE-AD1, NCT03334396; BREEZE-AD2, NCT03334422; BREEZE-AD7, NCT03733301.
RESUMEN
IMPORTANCE: Baricitinib, an oral selective Janus kinase inhibitor, improved the clinical signs and symptoms of moderate to severe atopic dermatitis in the 16-week, phase 3 monotherapy studies, BREEZE-AD1 and BREEZE-AD2. Long-term efficacy has not yet been examined. OBJECTIVE: To evaluate the long-term (68-week) efficacy of baricitinib in adults with moderate to severe atopic dermatitis who were treatment responders or partial responders in BREEZE-AD1 and BREEZE-AD2. DESIGN, SETTING, AND PARTICIPANTS: Patients completing BREEZE-AD1/BREEZE-AD2 entered the ongoing, multicenter, double-blind, long-term extension study BREEZE-AD3. The study was initiated on March 28, 2018. Data were analyzed on December 13, 2019. INTERVENTIONS: Responders and partial responders (patients achieving validated Investigator Global Assessment for Atopic Dermatitis [vIGA-AD] score of 0 or 1 [0,1], or 2) at BREEZE-AD1/BREEZE-AD2 completion remained on originally assigned treatment for 52 weeks (68 total weeks of continuous therapy). MAIN OUTCOMES AND MEASURES: The primary end point was the proportion of patients achieving a vIGA-AD score of 0,1 at weeks 16, 36, and 52 of BREEZE-AD3. Secondary end points included the proportion of patients achieving 75% or more improvement in the Eczema Area and Severity Index [EASI75] score and 4-point or more improvement in the itch numeric rating scale (NRS), using originating study baseline data. Itch data were collected during the first 16 weeks in BREEZE-AD3. The last originating study visit was the first BREEZE-AD3 visit; therefore, data are presented for continuous weeks of therapy, including the 16-week originating study period. Missing data were imputed by last observation carried forward. Modified intention-to-treat analysis was used. RESULTS: Of the responder/partial responder population, the proportion of patients treated with baricitinib, 4 mg (n = 70) (mean [SD] age, 36.7 [15.5] years; 42 [60%] were men), achieving vIGA-AD (0,1) at week 16 was 45.7% (BREEZE-AD3 baseline) and, at week 68, 47.1%. Improvement of 75% or more in the EASI score was 70.0% at week 16 and 55.7% at week 68. The proportion of patients achieving an itch NRS improvement greater than or equal to 4 points at week 16 was 52.5% and, at week 32, 45.9%. Of the responder/partial responder population, the proportion of patients treated with baricitinib, 2 mg (n = 54) (mean [SD] age, 32.8 [12.7] years; 28 [51.9%] were men), achieving vIGA-AD (0,1) at week 16 was 46.3% and, at week 68, 59.3%. Improvement in the EASI75 score was 74.1% at week 16 and 81.5% at week 68. The proportion of patients achieving an itch NRS improvement greater than or equal to 4 points at week 16 was 44.2% and, at week 32, 39.5%. CONCLUSIONS AND RELEVANCE: In this long-term double-blind extension study of 2 randomized clinical trials, baricitinib, 4 and 2 mg, demonstrated sustained long-term efficacy in patients with moderate to severe atopic dermatitis. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03334435.
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Azetidinas , Dermatitis Atópica , Adulto , Azetidinas/uso terapéutico , Dermatitis Atópica/complicaciones , Dermatitis Atópica/diagnóstico , Dermatitis Atópica/tratamiento farmacológico , Método Doble Ciego , Humanos , Masculino , Purinas/uso terapéutico , Pirazoles/uso terapéutico , Índice de Severidad de la Enfermedad , Sulfonamidas/uso terapéutico , Resultado del TratamientoRESUMEN
BACKGROUND: Baricitinib, an oral selective Janus kinase 1/Janus kinase 2 inhibitor, is being studied for moderate-to-severe atopic dermatitis (AD) in adults. OBJECTIVE: To evaluate the efficacy and safety of baricitinib monotherapy in a North American phase 3 trial (BREEZE-AD5/NCT03435081) of adults with moderate-to-severe AD who responded inadequately or were intolerant to topical therapy. METHODS: Patients (N = 440) were randomized 1:1:1 to once-daily placebo or baricitinib (1 mg or 2 mg). The primary endpoint was the proportion of patients achieving ≥75% reduction in the Eczema Area and Severity Index at week 16. A key secondary endpoint was the proportion of patients achieving a validated Investigator Global Assessment for AD score of 0 (clear)/1(almost clear) with ≥2-point improvement. RESULTS: At week 16, the proportion of patients achieving Eczema Area and Severity Index was 8%, 13%, and 30% (P < .001, 2 mg vs placebo) and those with a validated Investigator Global Assessment for AD score of 0/1 were 5%, 13%, and 24% (P < .001, 2 mg vs placebo) for placebo, baricitinib 1 mg, and baricitinib 2 mg, respectively. Safety findings were similar to those of other baricitinib AD studies. LIMITATIONS: Short-term clinical trial results may not be generalizable to real-world settings. CONCLUSION: Baricitinib was efficacious for patients with moderate-to-severe AD with no new safety findings over 16 weeks.
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Azetidinas/administración & dosificación , Dermatitis Atópica/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/administración & dosificación , Purinas/administración & dosificación , Pirazoles/administración & dosificación , Sulfonamidas/administración & dosificación , Adulto , Azetidinas/efectos adversos , Canadá , Dermatitis Atópica/diagnóstico , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Inhibidores de Proteínas Quinasas/efectos adversos , Purinas/efectos adversos , Pirazoles/efectos adversos , Índice de Severidad de la Enfermedad , Sulfonamidas/efectos adversos , Resultado del Tratamiento , Estados UnidosRESUMEN
OBJECTIVE: The Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) is validated for measuring fatigue in rheumatoid arthritis (RA). However, 10 of 13 FACIT-F items are identified as relevant to patients with RA. The Patient-Reported Outcomes Measurement Information System (PROMIS) uses an item response theory-calibrated T score metric. The PROMIS Fatigue item bank includes the FACIT-F items, enabling score conversion. The performance of converted PROMIS Fatigue scores has not been evaluated in RA populations or clinical trials. Our objective was to assess the performance of converted PROMIS Fatigue scores in 2 RA clinical trials of baricitinib. METHODS: Crosswalk tables and pattern-scoring methods converted FACIT-F scores to PROMIS Fatigue for both the 13-item FACIT-F and the 10-item RA-optimized FACIT-F instrument, in 2 RA clinical trials evaluating baricitinib, RA-BEAM, and RA-BEACON. RA-BEAM patients had an inadequate response to methotrexate. RA-BEACON patients had an inadequate response or intolerance to ≥1 tumor necrosis factor inhibitor. Baricitinib was compared to all treatment arms via analysis of covariance on PROMIS Fatigue score conversions. RESULTS: Baseline FACIT-F-derived PROMIS Fatigue scores reflected severe fatigue across treatment groups and were similar using different scoring methods. At week 24 in both studies, baricitinib was associated with clinically meaningful improvements in PROMIS Fatigue scores. PROMIS Fatigue scores were consistent for conversion methods and for the 13-item or 10-item FACIT-F. CONCLUSION: All 4 conversion methods showed differentiation of active treatment compared with placebo from week 12, supporting the use of the PROMIS Fatigue and converting the 10-item FACIT-F to assess fatigue and demonstrate treatment benefit in RA clinical trials on a standardized metric.
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Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Azetidinas/uso terapéutico , Fatiga/tratamiento farmacológico , Indicadores de Salud , Inhibidores de las Cinasas Janus/uso terapéutico , Medición de Resultados Informados por el Paciente , Purinas/uso terapéutico , Pirazoles/uso terapéutico , Sulfonamidas/uso terapéutico , Adulto , Anciano , Antirreumáticos/efectos adversos , Artritis Reumatoide/diagnóstico , Artritis Reumatoide/fisiopatología , Azetidinas/efectos adversos , Enfermedad Crónica , Ensayos Clínicos Fase III como Asunto , Fatiga/diagnóstico , Fatiga/fisiopatología , Femenino , Humanos , Inhibidores de las Cinasas Janus/efectos adversos , Masculino , Persona de Mediana Edad , Estudios Multicéntricos como Asunto , Valor Predictivo de las Pruebas , Purinas/efectos adversos , Pirazoles/efectos adversos , Ensayos Clínicos Controlados Aleatorios como Asunto , Inducción de Remisión , Sulfonamidas/efectos adversos , Factores de Tiempo , Resultado del TratamientoRESUMEN
Skin pain is increasingly recognized as an impactful symptom in atopic dermatitis (AD) because of its association with patient discomfort, disease burden, and reduced quality of life. Although the nature of skin pain in AD has not been systematically studied and is therefore not well understood, patients report soreness, discomfort, and tenderness that may reflect peripheral and central pain sensitization. The high prevalence of skin pain suggests that it is not adequately addressed by current therapies for AD and may be undertreated compared with other symptoms. This review discusses the clinical relevance of skin pain with respect to its experience, pathophysiology, relationship with itch, and treatment implications. Recent studies suggest that skin pain presents as a neuropathic symptom independent from itch and the “itch-scratch cycle”, and poses a unique burden to patients. Recognition of the significant consequences of skin pain and discomfort should reinforce the need to assess and treat this symptom in patients with moderate-to-severe AD. J Drugs Dermatol. 2020;19(10)921-926. doi:10.36849/JDD.2020.5498.
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Dermatitis Atópica/diagnóstico , Dolor/inmunología , Prurito/diagnóstico , Calidad de Vida , Costo de Enfermedad , Dermatitis Atópica/complicaciones , Dermatitis Atópica/inmunología , Dermatitis Atópica/psicología , Humanos , Dolor/diagnóstico , Dolor/epidemiología , Dimensión del Dolor , Prevalencia , Prurito/inmunología , Prurito/psicología , Índice de Severidad de la Enfermedad , Piel/inmunología , Piel/inervación , Piel/patología , Encuestas y CuestionariosRESUMEN
BACKGROUND: Atopic dermatitis (AD) has a negative impact on patients’ quality of life (QoL). OBJECTIVE: To report the impact of specific AD lesion locations on QoL in adult patients with AD using real-world data. METHODS: The Adelphi US Disease Specific Programme was conducted between January–April 2018. Physicians documented patient demographics/characteristics, AD lesion locations, and body surface area; patients completed questionnaires reporting the impact of lesion locations on QoL. RESULTS: AD severity was moderate in 51.6% of patients and severe in 6.0%. Lesions were commonly identified in more than one location. All AD lesion locations impacted QoL. Visible areas were most bothersome, including head/neck (68%), hands/fingers (58%), front (30%), upper extremities (22%), and lower extremities (16%), with statistically significant associations for a number of Dermatology Life Quality Index (DLQI) items. Itch, soreness, pain, and stinging are also associated with a number of body areas but in particular with those that are most visible/accessible. Lesions on the head/neck and hands/fingers (58%) demonstrated an increased impact on the anxiety and depression dimension of the EuroQol 5-Dimension tool. CONCLUSIONS: In patients with AD, quality of life was most affected in patients with lesions in visible areas, including head/neck, hands/fingers, and upper extremities, with statistically significant associations for a number of DLQI domains. Physicians should be aware of the burden of AD lesions on QoL and consider having conversations with patients to better understand the impact of these lesions. Prior presentation: 28th Annual European Academy of Dermatology and Venereology Congress; 9–13 October 2019, Madrid, Spain. Poster number P0233.J Drugs Dermatol. 2020;19(10): 943-948. doi:10.36849/JDD.2020.5422.
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Dermatitis Atópica/psicología , Calidad de Vida , Piel/patología , Adulto , Dermatitis Atópica/diagnóstico , Dermatitis Atópica/inmunología , Dermatitis Atópica/patología , Estética , Femenino , Mano , Cabeza , Humanos , Extremidad Inferior , Masculino , Persona de Mediana Edad , Cuello , Índice de Severidad de la Enfermedad , Piel/inmunología , Encuestas y Cuestionarios , Adulto JovenRESUMEN
Importance: Baricitinib, an oral selective Janus kinase 1 and 2 inhibitor, effectively reduced disease severity in moderate to severe atopic dermatitis (AD) in 2 phase 3 monotherapy studies. Objective: To assess the efficacy and safety of 4 mg and 2 mg of baricitinib in combination with background topical corticosteroid (TCS) therapy in adults with moderate to severe AD who previously had an inadequate response to TCS therapy. Design, Setting, and Participants: This double-blind, placebo-controlled, phase 3 randomized clinical trial, BREEZE-AD7 (Study of Baricitinib [LY3009104] in Combination With Topical Corticosteroids in Adults With Moderate to Severe Atopic Dermatitis) was conducted from November 16, 2018, to August 22, 2019, at 68 centers across 10 countries in Asia, Australia, Europe, and South America. Patients 18 years or older with moderate to severe AD and an inadequate response to TCSs were included. After completing the study, patients were followed up for up to 4 weeks or enrolled in a long-term extension study. Interventions: Patients were randomly assigned (1:1:1) to receive 2 mg of baricitinib once daily (n = 109), 4 mg of baricitinib once daily (n = 111), or placebo (n = 109) for 16 weeks. The use of low-to-moderate potency TCSs was allowed. Main Outcomes and Measures: The primary end point was the proportion of patients achieving a validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) score of 0 (clear) or 1 (almost clear), with a 2-point or greater improvement from baseline at week 16. Results: Among 329 patients (mean [SD] age, 33.8 [12.4] years; 216 [66%] male), at week 16, a vIGA-AD score of 0 (clear) or 1 (almost clear) was achieved by 34 patients (31%) receiving 4 mg of baricitinib and 26 (24%) receiving 2 mg of baricitinib compared with 16 (15%) receiving placebo (odds ratio vs placebo, 2.8 [95% CI, 1.4-5.6]; P = .004 for the 4-mg group; 1.9 [95% CI, 0.9-3.9]; P = .08 for the 2-mg group). Treatment-emergent adverse events were reported in 64 of 111 patients (58%) in the 4-mg group, 61 of 109 patients (56%) in the 2-mg group, and 41 of 108 patients (38%) in the placebo group. Serious adverse events were reported in 4 patients (4%) in the 4-mg group, 2 (2%) in the 2-mg group, and 4 (4%) in the placebo group. The most common adverse events were nasopharyngitis, upper respiratory tract infections, and folliculitis. Conclusions and Relevance: A dose of 4 mg of baricitinib in combination with background TCS therapy significantly improved the signs and symptoms of moderate to severe AD, with a safety profile consistent with previous studies of baricitinib in AD. Trial Registration: ClinicalTrials.gov Identifier: NCT03733301.
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Azetidinas/administración & dosificación , Dermatitis Atópica/tratamiento farmacológico , Glucocorticoides/administración & dosificación , Purinas/administración & dosificación , Pirazoles/administración & dosificación , Sulfonamidas/administración & dosificación , Administración Cutánea , Administración Oral , Adulto , Azetidinas/efectos adversos , Dermatitis Atópica/diagnóstico , Dermatitis Atópica/inmunología , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Esquema de Medicación , Quimioterapia Combinada/efectos adversos , Quimioterapia Combinada/métodos , Femenino , Foliculitis/inducido químicamente , Foliculitis/epidemiología , Foliculitis/inmunología , Glucocorticoides/efectos adversos , Humanos , Janus Quinasa 1/antagonistas & inhibidores , Janus Quinasa 1/metabolismo , Janus Quinasa 2/antagonistas & inhibidores , Janus Quinasa 2/metabolismo , Masculino , Persona de Mediana Edad , Nasofaringitis/inducido químicamente , Nasofaringitis/epidemiología , Nasofaringitis/inmunología , Purinas/efectos adversos , Pirazoles/efectos adversos , Infecciones del Sistema Respiratorio/inducido químicamente , Infecciones del Sistema Respiratorio/epidemiología , Infecciones del Sistema Respiratorio/inmunología , Índice de Severidad de la Enfermedad , Transducción de Señal/efectos de los fármacos , Transducción de Señal/inmunología , Sulfonamidas/efectos adversos , Adulto JovenRESUMEN
BACKGROUND: An Investigator Global Assessment (IGA) is recommended by health agencies for drug registration in atopic dermatitis (AD). Current IGA scales lack standardization. OBJECTIVES: To develop an IGA scale, training module, and clinical certification examination for use in AD trials; establish content validity; and assess reliability. METHODS: Expert dermatologists participated in the development of the validated IGA for AD (vIGA-ADTM). Reliability (interrater and intrarater) was assessed by 2 web-based surveys. Clinical certification for investigators consisted of a training module and examination. RESULTS: Expert consensus was achieved around a 5-point IGA scale including morphologic descriptions, and content validity was established. Survey 1 showed strong interrater reliability (Kendall's coefficient of concordance W [Kendall's W], 0.809; intraclass correlation [ICC], 0.817) and excellent agreement (weighted kappa, 0.857). Survey 2, completed 5 months after training of dermatologists, showed improvements in scale reliability (Kendall's W, 0.819; ICC, 0.852; weighted kappa, 0.889). In this study, 627 investigators completed vIGA-AD training and certification. LIMITATIONS: Ratings were assessed on photographs. CONCLUSION: A validated IGA scale and training module were developed with the intent of harmonizing assessment of disease severity in AD trials. Strong reliability and excellent agreement between assessments were observed.
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Consenso , Dermatitis Atópica/diagnóstico , Evaluación de Resultado en la Atención de Salud/normas , Índice de Severidad de la Enfermedad , Adulto , Niño , Conferencias de Consenso como Asunto , Dermatitis Atópica/terapia , Dermatólogos/normas , Dermatólogos/estadística & datos numéricos , Humanos , Variaciones Dependientes del Observador , Fotograbar , Reproducibilidad de los Resultados , Piel/diagnóstico por imagen , Encuestas y Cuestionarios/estadística & datos numéricos , TelecomunicacionesRESUMEN
INTRODUCTION: Many rheumatoid arthritis (RA) patients do not achieve their treatment goals and experience symptoms that affect psychosocial outcomes and daily activities. This study aimed to identify and quantify the unmet needs perceived by US patients with RA currently taking a disease-modifying antirheumatic drug (DMARD). METHODS: A cross-sectional, web-based survey was conducted with RA patients recruited through CreakyJoints, an online patient support community, and ArthritisPower®, an online patient research registry, from December 2017 to January 2018. Participant patients were aged ≥ 21 years, failed ≥ 1 DMARDs, and were receiving their current DMARD(s) for ≥ 6 months; they answered 50 questions about treatment history, RA symptoms, and flares and completed the Rheumatoid Arthritis Impact of Disease (RAID) questionnaire and the Treatment Satisfaction Questionnaire for Medication (TSQM). Treatment satisfaction was defined by a TSQM global satisfaction score ≥ 80. RESULTS: Of 415 patients screened, 258 (62%) were eligible and completed the survey; 87% were women, and 87% white, with mean (SD) age of 54.5 (11.4) years. A total of 232 patients (90%) had current or past biologic DMARD (bDMARD) use, with 67% currently on a bDMARD, 65% on ≥ 1 conventional synthetic DMARD, and 40% on methotrexate. Forty-three percent of patients reported daily/almost daily use of prescription pain medications, and 44% reported a current flare. Mean (SD) TSQM scores were 59 [20] for effectiveness, 59 [26] for side effects, 72 [18] for convenience, and 65 [21] for global satisfaction. The mean (SD) RAID overall score was 5.1 (2.0) on a 0-10 scale. Only 26% (67 patients) were satisfied with their RA treatment. Patients not satisfied with treatment reported higher RAID scores overall and by domain, and approximately half reported a current flare. CONCLUSIONS: Results from this real-world survey suggest that three-fourths of RA patients are not satisfied with treatments, which include bDMARDs. Patients continued to experience bothersome symptoms that impacted their daily activities and life. There remains a need for improved disease management among currently treated RA patients. FUNDING: Eli Lilly and Company (Indianapolis, IN, USA).
RESUMEN
BACKGROUND: Atopic dermatitis (AD) is a common skin disorder characterized by chronic inflammation, altered skin barrier function, and inflammatory cell skin infiltration that decreases health-related quality of life (HRQoL). The study objective was to understand the patient perspective of AD burden and determine suitable patient-reported outcome (PRO) measures. METHODS: This mixed methods study involved the collection of qualitative and quantitative information from adults (≥ 18 years old) and adolescents (12 - 17 years old) with clinician-confirmed AD regarding their experiences of AD symptoms and its impact on HRQoL. The first part of the study included three stages: in-person concept elicitation (CE) interviews, a 2-week daily electronic diary (eDiary) study, and in-person cognitive debriefing (CD) interviews. An Itch numeric rating scale (NRS) (v1.0) and a Skin Pain NRS (v1.0) evaluation during CD interviews required participants to think about their 'worst' itch and 'worst' skin pain in the past 24 h. Other PRO measures allowed for psychometric testing. The second part of the study involved telephone-depth interviews (TDIs) and qualitative feedback from participants who had not participated in the CD interviews. Qualitative data were thematically analyzed. Psychometric evaluation of NRS measures was performed using eDiary data. RESULTS: In the CE interviews, itch and/or itching and skin pain were the most prevalent symptoms consistently discussed by participants. Both NRS measures demonstrated strong psychometric reliability and were applicable across ages with suitable concurrent validity. During the CD interviews, some participants focused their answers on their 'average' itch/itching in the past 24 h, rather than their 'worst' itch. Some participants answered the Skin Pain NRS thinking about general pain or other types of pain, rather than skin pain specifically. Consequently, modifications to both measures addressed these issues and re-tested as paper-and-pen versions in subsequent TDIs. Itch NRS (v2.0) modifications helped participants focus on their worst itching. Most participants preferred Skin Pain NRS v2.0b, which included skin pain descriptors. CONCLUSIONS: Itching and skin pain are the most important and relevant AD symptoms. The Itch NRS (v2.0) and Skin Pain NRS (v2.0b) appear to be appropriate endpoints for the assessment of itching and skin pain severity for clinical trials with adults and adolescents with AD.
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INTRODUCTION: To explore the relationship of pain and fatigue with daily activity and work productivity in rheumatoid arthritis (RA) patients from the baricitinib clinical trial, RA-BEAM. METHODS: In RA-BEAM, a double-blind phase 3 study, patients were randomized 3:3:2 to placebo (n = 488), baricitinib 4 mg once daily (n = 487), or adalimumab 40 mg biweekly (n = 330) with background methotrexate. The Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) measured fatigue and the pain visual analog scale (0-100 mm) assessed pain. Work Productivity and Activity Impairment Questionnaire-RA measured daily activity and work productivity. At weeks 12 and 24, pain was assessed using pain reduction (< 30%, 30% to < 50%, ≥ 50%) and overall pain score; clinically relevant FACIT-F changes were assessed by values < 3.56 and ≥ 3.56 and the FACIT-F normative value score (< 40.1, ≥ 40.1). Pairwise comparisons between pain/fatigue reduction groups were assessed using ANCOVA with pooled data on daily activity and work productivity. A mediator analysis with pain, fatigue, and disease activity measured their contribution to daily activity and work productivity. Data were pooled from all patients for most analyses, and baricitinib-treated patients were assessed as a sensitivity analysis. RESULTS: Reductions in pain (≥ 50%) and fatigue (≥ 3.56) had significant (p ≤ 0.001) effects on daily activity and work productivity improvement at weeks 12 and 24. Reductions in pain, fatigue, and disease activity accounted for most of the improvements in daily activity and work productivity. At the lowest levels of remaining pain (≤ 10 mm) at weeks 12 and 24, however, fatigue did not appear to impact work productivity. Similar trends were observed with baricitinib-treated patients. CONCLUSIONS: Reductions in pain and fatigue were associated with improved daily activity and work productivity for all RA patients and for baricitinib-treated patients in RA-BEAM. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT01710358. FUNDING: Incyte Corporation and Eli Lilly and Company.
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After publication of the original article [1], the authors have notified us of an error in language used in the text.