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Summary 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.

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.

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.

Background Atopic dermatitis (AD) is a common, chronic, relapsing, inflammatory skin disease causing a variety of dermatologic signs and symptoms, affecting patientrs quality of life. While treatment options are available, they are of variable effectiveness. This study sought to characterize patient-reported AD signs and symptoms, flare, and associated bother, by disease severity and control. Methods Adults diagnosed with AD were recruited through the National Eczema Association (NEA) and clinical sites and completed a web-based survey including the Patient-Oriented SCORing Atopic Dermatitis (PO-SCORAD), Recap of Atopic Eczema (RECAP), and Skin Pain numeric rating scale (NRS), as well as questions on previous/current clinical presentation, flare frequency and severity, past/ present AD treatment, and sociodemographic characteristics. Results A total of 186 participants completed the survey (mean age 39.7 years, 80% female). The most frequently reported current AD signs and symptoms included dryness, itch, redness, roughness, and flaking skin, and the most bothersome were itch, dryness, and redness (63%). The majority of participants (84%) were either currently experiencing a flare or had experienced one within the past month. The most common signs and symptoms that grew worse during the most recent flare were itch and redness across all disease severity groups. Participants most often experienced one to three flares in the last three months. Flare frequency, duration, and average severity increased with greater disease severity and lack of disease control. Conclusions The results of this study demonstrate the diverse and considerable symptomatic burden experienced by people with AD, even while being treated for AD. J Drugs Dermatol. 2021;20(11):1222-1230. doi:10.36849/JDD.6329.

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.

Baricitinib, an oral selective Janus kinase 1/Janus kinase 2 inhibitor, is being studied for moderate-to-severe atopic dermatitis (AD) in adults.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.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.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.Short-term clinical trial results may not be generalizable to real-world settings.Baricitinib was efficacious for patients with moderate-to-severe AD with no new safety findings over 16 weeks.

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.

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.

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.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.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) (P0.001 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) (P0.001 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.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.).

Background Atopic dermatitis (AD) has a negative impact on patientsr 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 JanuarynApril 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; 9n13 October 2019, Madrid, Spain. Poster number P0233.J Drugs Dermatol. 2020;19(10): 943-948. doi:10.36849/JDD.2020.5422.

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 theldquo;itch-scratch cyclerdquo;, 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.

Contains fulltext : 225356.pdf (Publisher’s version ) (Closed access) 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-AD(TM)). 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.

BACKGROUND Baricitinib, an oral selective Janus kinase 1 and 2 inhibitor, effectively reduced atopic dermatitis (AD) severity in a phase II study with concomitant topical corticosteroids. OBJECTIVES To evaluate the efficacy and safety of baricitinib in patients with moderate-to-severe AD who had an inadequate response to topical therapies. METHODS In two independent, multicentre, double-blind, phase III monotherapy trials, BREEZE-AD1 and BREEZE-AD2, adults with moderate-to-severe AD were randomized 2 : 1 : 1 : 1 to once-daily placebo, baricitinib 1 mg, 2 mg, or 4 mg for 16 weeks. RESULTS At week 16, more patients achieved the primary end point of Validated Investigator's Global Assessment of AD (0, 1) on baricitinib 4 mg and 2 mg compared with placebo in BREEZE-AD1 [N = 624; baricitinib 4 mg 16·8% (P < 0·001), 2 mg 11·4% (P < 0·05), 1 mg 11·8% (P < 0·05), placebo 4·8%], and BREEZE-AD2 [N = 615; baricitinib 4 mg 13·8% (P = 0·001), 2 mg 10·6% (P < 0·05), 1 mg 8·8% (P = 0·085), placebo 4·5%]. Improvement in itch was achieved as early as week 1 for 4 mg and week 2 for 2 mg. Improvements in night-time awakenings, skin pain and quality-of-life measures were observed by week 1 for both 4 mg and 2 mg (P ≤ 0·05, all comparisons). The most common adverse events in patients treated with baricitinib were nasopharyngitis and headache. No cardiovascular events, venous thromboembolism, gastrointestinal perforation, significant haematological changes, or death were observed with any baricitinib dosage. CONCLUSIONS Baricitinib improved clinical signs and symptoms in patients with moderate-to-severe AD within 16 weeks of treatment and induced rapid reduction of itch. The safety profile remained consistent with prior findings from baricitinib clinical development in AD, with no new safety concerns.

PurposeAlopecia 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.ParticipantsA 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 dateThe 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 plansObservational 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.

Background: Itch, skin pain, and sleep disturbance are burdensome symptoms in atopic dermatitis (AD) that negatively influence a patient’s quality of life (QoL). Objective: To evaluate the impact of baricitinib on patient-reported outcomes (PROs) in adult patients with moderate-to-severe AD, and explore the association between improvement in key signs and symptoms of AD with improvements in QoL and patient’s assessment of disease severity. Methods: Data were analyzed from two phase III monotherapy trials (BREEZE-AD1/BREEZE-AD2) in which patients were randomized 2:1:1:1 to once-daily placebo, baricitinib 1-mg, 2-mg, or 4-mg for 16 weeks and assessed using PRO measures. Results: At week 16, baricitinib 4-mg and 2-mg significantly reduced itch severity (Itch Numeric Rating Scale (NRS) (BREEZE-AD1: percent change from baseline −36.6% and −29.4% vs. placebo (–12.0%), p≤.001 and p≤.05; BREEZE-AD2: −47.2% and −46.9% vs. placebo (–16.6%), p≤.001). Baricitinib significantly reduced SCORing AD (SCORAD) pruritus (4-mg in BREEZE-AD1 and 2-mg in BREEZE-AD2) and Patient Oriented Eczema Measure (POEM) itch (both doses). Improvements in skin pain severity and sleep disturbance were also observed. Improvements in AD symptoms showed higher correlations with patients’ assessment of AD severity and QoL than improvements in skin inflammation. Conclusions: Baricitinib significantly improved symptoms in patients with moderate-to-severe AD. ClinicalTrials.gov identifiers: NCT03334396 (BREEZE-AD1) and NCT03334422 (BREEZE-AD2).

Background The Itch Numeric Rating Scale (NRS), Skin Pain NRS, and Atopic Dermatitis Sleep Scale (ADSS) are self-administered patient-reported outcome (PRO) instruments developed to assess symptoms in patients with atopic dermatitis (AD). The objective of this study was to evaluate the psychometric properties (reliability, validity, and responsiveness) and interpretability thresholds of these PROs using data from three pivotal Phase 3 studies in adults. Methods BREEZE-AD1, BREEZE-AD2, and BREEZE-AD5 evaluated the safety and efficacy of baricitinib in adults with moderate-to-severe AD. Clinician-reported outcomes and other PROs commonly assessed in patients with AD were used to estimate meaningful changes and evaluate test–retest reliability, convergent and divergent validity, known-groups validity, responsiveness, and meaningful change thresholds (MCTs) of the Itch NRS, Skin Pain NRS, and ADSS. Results The test–retest reliability of the Itch NRS, Skin Pain NRS, and ADSS was evidenced by generally large intraclass correlation coefficients (> 0.7) in stable groups of patients between baseline and Week 1 and Weeks 4 and 8. Moderate-to-large correlations (r > 0.4) at baseline and Week 16 were generally observed between each measure and other PROs measuring the same concept, supporting convergent validity. Small-to-moderate correlations with clinician-reported outcomes demonstrated divergent validity. Each instrument was able to distinguish between known groups of disease severity as assessed using other indicators of AD severity. The responsiveness of the Itch NRS, Skin Pain NRS, and ADSS scales was demonstrated through significant differences in their change scores from baseline to Week 16 between categories of change in another PRO also from baseline to Week 16. Thresholds for interpreting meaningful change were estimated as − 4.0 for the 0–10 Itch and Skin Pain NRS items; − 1.25 for the 0–4 ADSS Items 1 and 3 and; − 1.50 for the 0–29 ADSS Item 2, these equivalent to moderate degrees of change. Conclusions Results of this study demonstrate that the psychometric properties of the Itch NRS, Skin Pain NRS, and ADSS are good to excellent. These findings support the use of these instruments in daily assessment of AD symptoms in adults with moderate-to-severe AD. Trial registration ClinicalTrials.gov numbers: NCT03334396, NCT03334422, and NCT03435081.

Introduction BREEZE-AD1 ( NCT03334396 ) et BREEZE-AD2 ( NCT03334422 ) sont les premieres de 7 etudes cliniques de phase 3 evaluant le baricitinib, un inhibiteur des JAK 1/2, dans le traitement de la dermatite atopique (DA) moderee a severe. Ces etudes evaluent l’efficacite et la tolerance du baricitinib dans la DA moderee a severe insuffisamment controlee par des traitements topiques chez l’adulte. Materiel et methodes BREEZE-AD1 et BREEZE-AD2 sont des etudes identiques de phase 3 randomisees, en double-aveugle, controlees versus placebo, en monotherapie. La randomisation s’effectuait en 2: 1: 1: 1 comprenant les bras placebo, baricitinib 1 mg, 2 mg ou 4 mg, tous les jours, pendant 16 semaines. Le critere de jugement principal etait le pourcentage de patients atteignant un score Validated Investigator's Global Assessement pour la DA (vIGA-AD) de 0 (blanchi) ou 1 (presque blanchi) avec une amelioration ≥ 2 points entre l’inclusion et S16. Des analyses avec ajustements multiples ont ete utilisees pour le critere principal et les criteres secondaires. Resultats Un nombre de patients significativement plus eleve a atteint le critere principal de vIGA-AD (0/1) dans les bras baricitinib 4 mg et 2 mg compare au placebo (baricitinib 4 mg 16,8 %/13,8 % [p Conclusion Le traitement par baricitinib a ameliore de facon significative les signes cliniques et symptomes de la DA moderee a severe versus placebo et represente une potentielle nouvelle option therapeutique.

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). Electronic Supplementary Material The online version of this article (10.1007/s40744-019-00168-5) contains supplementary material, which is available to authorized users.

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 (

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

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

Little is currently known about possible associations between disease specific characteristics of atopic dermatitis (AD) and use of medical treatments. We explored the use of AD treatments within the past 12 months in Danish adults according to distinct patient characteristics. Patients who had received a diagnosis of AD in a hospital in- or outpatient setting as adults were surveyed and data cross-linked to a national prescription registry. AD severity was measured by the Patient-Oriented SCORing Atopic Dermatitis (PO-SCORAD). A total of 3834 patients participated. Use of topical medication in the past 12 months increased with increasing AD severity, whereas no difference was observed for systemic medication use. Positive associations between AD in the face and neck, and use of mild and moderately potent topical corticosteroids were observed, while involvement of palms and chest was associated with use of more potent topical corticosteroids. The mean DLQI, skin pain, and itch severity scores were lower in patients managed only with topical corticosteroids (5.5, 3.2, and 4.3, respectively) compared to patients treated with both oral and topical medication (7.1, 3.8, and 5.0, respectively). Patients with frequent topical corticosteroid use tended to be older (50.7 vs 48.6 years), males (50.0% vs 33.6%), current daily smokers (17.3% vs 13.7%), and having asthma (59.1% vs 43.8%) compared with infrequent users of topical corticosteroids. We found a disconnect between the severity of AD signs and symptoms, and use of AD therapies. In particular, a very modest use of systemic immunosuppressants was seen even among patients with severe AD symptoms. However, the underlying clinical decisions and reasons behind this disconnect is not clear based on the current data.

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.

Introduction La monotherapie par le baricitinib, un inhibiteur selectif des JAK1/2, a reduit efficacement la gravite de la DA moderee a severe lors de precedentes etudes de phase 3. L’etude de phase 3 en double aveugle, randomisee et controlee par placebo BREEZE-AD7 (NCT03733301) a evalue l’efficacite et la securite du baricitinib associe a des TCS chez les adultes atteints de DA moderee a severe. Materiel et methodes La randomisation etait de 1 :1 :1 pour le placebo, le baricitinib 2 mg ou 4 mg pris par voie orale chaque jour pendant 16 semaines. L’utilisation d’un TCS de puissance faible a moderee etait autorisee. Le critere principal etait la proportion de patients avec un score de 0 (blanchi)/1 (quasi blanchi) de l’evaluation globale validee par l’investigateur pour la dermatite atopique (vIGA-AD™), avec une amelioration ≥ 2 points entre l’inclusion et la semaine 16. Resultats Au total, 329 patients ont ete inclus. La proportion de patients ayant atteint le critere principal etait significativement plus elevee avec la dose de 4 mg qu’avec le placebo (30,6 % vs 14,7 %, p ≤ 0,01). A la semaine 16, un nombre significativement plus eleve de patients a atteint un score EASI 75 avec 4 mg (47,7 %, p ≤ 0,01) et 2 mg (43,1 %, p ≤ 0,01) qu’avec le placebo (22,9 %). Une amelioration significative des demangeaisons a ete detectee des la semaine 2 pour 4 mg et des la semaine 3 pour 2 mg. Une amelioration des reveils nocturnes, des douleurs cutanees, du DLQI et du POEM a ete observee des la semaine 1 avec 4 mg et entre les semaines 1 a 3 pour 2 mg. Cette amelioration s’est maintenue jusqu’a la semaine 16. Le baricitinib a reduit de maniere significative la quantite de TCS de puissance moderee utilisee (39 % et 28 % [p ≤ 0,01] pour 4 mg et 2 mg, respectivement, vs placebo). Des evenements indesirables (EI) survenus en cours de traitement ont ete rapportes pour 38 %, 56 % et 58 % des patients, et des EI graves pour 3,7 %, 1,8 % et 3,6 % des patients sous placebo, 2 mg et 4 mg, respectivement. Les EI les plus frequents etaient des rhinopharyngites, des infections des voies aeriennes superieures, des folliculites. Une embolie pulmonaire a ete signalee dans le groupe 4 mg ; une infection opportuniste (toxoplasmose oculaire) a ete signalee dans le groupe placebo. Aucun cancer, evenement indesirable cardiovasculaire majeur ou deces n’a ete signale. Discussion Le baricitinib, associe a des TCS, a permis d’ameliorer de maniere significative les signes et symptomes de la DA moderee a severe par rapport au placebo. Les EI etaient comparables a ceux observes dans les precedentes etudes sur la DA.

Introduction Le baricitinib (bari), un inhibiteur selectif des Janus kinase (JAK) 1 et 2 administre par voie orale, a permis d’ameliorer significativement les signes et symptomes de la DA moderee a severe en monotherapie (BREEZE-AD1 et AD2) et associe a des corticosteroides topiques (TCS) de fond (BREEZE-AD7). Nous presentons les resultats de BREEZE-AD4 en matiere d’efficacite et de tolerance. Materiel et methodes Des patients adultes atteints de DA moderee a severe en echec, intolerance ou contre-indication a la CsA ont ete randomises (1:1:2:1) afin de recevoir un placebo (PBO, N = 93), bari 1 mg (N = 93), 2 mg (N = 185) ou 4 mg (N = 92) par jour. L’utilisation d’un TCS de puissance faible a moderee etait autorisee pour les lesions actives. Le critere principal etait la proportion de patients traites par bari 4 mg ou 2 mg presentant une amelioration ≥ 75 % de l’Eczema Area and Severity Index (EASI 75) a la semaine 16 par rapport a l’inclusion. Des analyses ajustees pour comparaisons multiples ont ete realisees sur les criteres principaux et secondaires majeurs. L’efficacite a ete analysee dans la population en intention de traiter. La tolerance a ete analysee pour les patients ayant pris ≥ 1 dose de bari. Resultats Sur les 463 patients randomises, 410 (89 %) ont atteint la 16eme semaine d’evaluation (n = 334 [72 %] sans traitement de secours ; n = 76 [16 %] avec traitement de secours). Parmi eux, le critere principal (EASI 75) a ete atteint chez 32 % (4 mg, p = 0,031), 28 % (2 mg, p = 0,071) et 17 % (PBO). Le traitement par bari 4 mg etait superieur au PBO pour les criteres secondaires majeurs d’amelioration ≥ 4 points sur l’echelle numerique d’evaluation (NRS) du prurit aux semaines 2, 4 et 16 ; le pourcentage moyen d’amelioration par rapport a l’inclusion (CFB) du score EASI a la semaine 16, le CFB moyen du NRS des douleurs cutanees a la semaine 16 et le CFB moyen de l’item 2 de l’ADSS (nombre de reveils nocturnes dus au prurit) a la semaine 16 (tableau ci-dessous). Des evenements indesirables apparus en cours de traitement (EICT) ont ete rapportes chez 53,8 % (PBO), 62,4 % (1 mg), 67,9 % (2 mg) et 75,0 % (4 mg) des patients ; des evenements indesirables graves ont ete rapportes chez 2,2 % (PBO), 4,3 % (1 mg), 1,6 % (2 mg) et 6,5 % (4 mg) des patients. EICT les plus frequents : rhinopharyngite et cephalee. Aucun evenement cardiovasculaire majeur, aucune thrombose veineuse (notamment embolie pulmonaire) ni aucun deces n’ont ete signales. Discussion Le traitement par bari 4 mg, associe a des TCS, etait superieur au PBO pour l’amelioration des signes et symptomes de la DA moderee a severe chez les patients en echec, intolerance ou contre-indications a la CsA. Soumis a l’EADV, la decision est en attente au moment de la soumission aux JDP.

BackgroundTo assess the effect of baricitinib on patient-reported outcomes (PROs) in patients with active rheumatoid arthritis and an inadequate response to methotrexate (MTX).MethodsIn this double-blind phase 3 study, patients were randomised 3:3:2 to placebo (n=488), baricitinib 4 mg once daily (n=487), or adalimumab 40 mg biweekly (n=330) with background MTX. PROs included the SF-36, EuroQol 5-D (EQ-5D) index scores and visual analogue scale, Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), Health Assessment Questionnaire-Disability Index (HAQ-DI), Patient’s Global Assessment of Disease Activity (PtGA), patient’s assessment of pain and Work Productivity and Activity Impairment Questionnaire-Rheumatoid Arthritis (WPAI-RA), and measures collected in electronic patient daily diaries: duration and severity of morning joint stiffness (MJS), Worst Ttiredness and Worst Joint Pain. The primary study endpoint was at week 12. Treatment comparisons were assessed with logistic regression for categorical measures or analysis of covariance for continuous variables.ResultsCompared with placebo and adalimumab, baricitinib showed statistically significant improvements (p≤0.05) in HAQ-DI, PtGA, pain, FACIT-F, SF-36 physical component score, EQ-5D index scores and WPAI-RA daily activity at week 12. Improvements were maintained for measures assessed to week 52. Statistically significant improvement in patient diary measures (MJS duration and severity), worst tiredness and worst joint pain were observed for baricitinib versus placebo and adalimumab at week 12 (p≤0.05).ConclusionsBaricitinib provided significantly greater improvement in most PROs compared with placebo and adalimumab, including physical function MJS, pain, fatigue and quality of life. Improvement was maintained to the end of the study (week 52).Trial registrationNCT01710358.

Background Baricitinib (Bari), an oral selective inhibitor of Janus kinase (JAK)1 and JAK2, has been approved for the treatment of rheumatoid arthritis (RA) in over 50 countries including the United States, European countries, and Japan. The purpose of this study was to report results from a 24 week global, Phase 2, double-blind, placebo (PBO)-controlled study of Bari in patients with systemic lupus erythematosus (SLE) receiving standard therapy. Methods Patients with SLE (positive antinuclear antibody [ANA] or anti-double stranded DNA [anti-dsDNA], clinical SLE Disease Activity Index 2000 [SLEDAI-2K] 4, arthritis or rash required) receiving stable background SLE therapy were randomized 1:1:1 to PBO or Bari (2- or 4 mg) once-daily. The primary endpoint was resolution of arthritis or rash as defined by the SLEDAI-2K at Week 24. Results Of 314 patients randomized, 79%, 82%, and 83% completed 24 weeks of treatment in the PBO, Bari 2 mg, and Bari 4 mg groups, respectively. At Week 24, a significantly greater proportion of patients in the Bari 4 mg group compared to PBO achieved resolution of arthritis or rash (67% vs 53%, p Conclusions In patients with SLE receiving standard background therapy, once-daily oral Bari 4 mg was associated with significant clinical improvements compared to PBO and an acceptable benefit/risk profile. These findings support further study of Bari as a potential therapy for patients with SLE. Funding Source(s): This study was funded by Eli Lilly and Company.

Rheumatoid arthritis (RA) is associated with significantly diminished health-related quality of life. Patient-reported outcomes (PROs) are considered important in RA; however, some symptoms such as morning joint stiffness (MJS) and fatigue that are considered important by patients are not captured by the American College of Rheumatology “core set” measures for RA trials. The US Food and Drug Administration has endorsed electronic capture of clinical trial data including PROs, and electronic PRO (ePRO) systems may lead to more accurate and complete data capture, improved compliance, and patient acceptance compared with paper-based methods. Our objective was to assess the implementation of ePRO measures of Duration and Severity of MJS, Severity of Worst Tiredness, and Severity of Worst Joint Pain in baricitinib RA-BEAM and RA-BUILD phase 3 randomized clinical trials (RCTs). A daily electronic diary (handheld device; Invivodata®, Inc.) was utilized to capture PRO data in the RCTs. Three “reporting window” options were incorporated to accommodate differences in patients’ routine daily schedules, and alarms were programmed for each reporting window. Duration of MJS was recorded in “hours and minutes,” and Severity of MJS, Worst Tiredness, and Worst Joint Pain were captured on a 0 to 10 rating scale, with a higher score indicating more severe symptoms. The patients and site staff were trained to use the daily electronic diary. Patients with moderately to severely active RA used the daily electronic diary in the RA-BEAM study (N = 1305) and RA-BUILD study (N = 684). The average compliance, calculated as total days completed by patients compared with total days expected to complete the diary, through Week 12 was high (RA-BEAM 94% patients; RA-BUILD 93% patients), potentially attributable to appropriate training, clarity of instructions, simple user interface, and electronic device design. Identified process challenges included non-timely issuance of the device, low battery, inadequate training of patients before data collection, inappropriate diary set-up, and first response entry 1 day after the baseline visit. High compliance rates support the use of the daily electronic PRO diary in large RCTs. Despite the anticipated issues, the daily electronic diary is expected to reduce recall bias and improve the quality of PRO data collection. RA-BEAM ( NCT01710358 ) and RA-BUILD ( NCT01721057 ).

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.

Background: The objectives of this systematic review and meta-analysis were to compare the survival, toxicity, and quality of life of patients treated with necitumumab in combination with gemcitabine and cisplatin. These agents were investigated in published randomized controlled trials (RCTs) of patients with squamous non-small cell lung cancer (NSCLC) in the first-line setting. Methods: The systematic review was executed on January 27, 2015, and updated on August 21, 2016, using a pre-specified search strategy. Searches were conducted using PubMed, Medline, and EMBASE, with supplemental searches using the Evidence Based Medicine Reviews and ClinicalTrials.gov to identify RCTs published in English from 1995–2016 and reporting at least one of the primary outcomes [overall survival (OS), progression-free survival (PFS), toxicity, or quality of life] in patients who received first-line treatment for advanced or metastatic squamous NSCLC. Study quality and risk of bias were assessed using the Physiotherapy Evidence Database (PEDro) scale and Cochrane risk of bias tool, respectively. A Baysian network meta-analysis was performed on the primary outcomes. Hazard ratios (HRs) were evaluated for the primary analysis; secondary analyses were conducted using median OS data. Planned sensitivity analyses were conducted including reanalysis using a Frequentist approach and limiting analyses to subsets based on clinical and demographic covariates. Results: The systematic literature review resulted in identification of 4,016 unique publications; 40 publications (35 unique trials) were eligible for inclusion. Eight studies connected to a common network for the OS analysis using HR data. The majority of studies were not limited to squamous NSCLC, thus analyzable data were limited to a subset of data within the published trials. Carboplatin + S-1 and necitumumab in combination with gemcitabine and cisplatin were associated with lower HRs for OS versus all other comparators. Nine studies connected to the network for the PFS analysis in which necitumumab in combination with gemcitabine and cisplatin was associated with the lowest HR. Data were not available to analyze toxicity or quality of life. Conclusions: Although the results suggest that carboplatin + S-1 and necitumumab in combination with gemcitabine and cisplatin may have value in terms of OS versus other comparators, the results should be interpreted with caution due to the limited number of studies (with few focused exclusively on squamous NSCLC) and wide credible intervals.

Background Fatigue and pain in patients (pts) with RA are often measured with the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) and the Medical Outcomes Study Short-Form-36 (SF-36). Patient-Reported Outcomes Measurement Information System (PROMIS) was developed using a population-calibrated T-score metric (Mean 50, SD 10). Crosswalk tables were developed linking legacy instruments to PROMIS instruments, including Fatigue and Pain Interference (PI). Comparisons to the general population can be made from PROMIS scores.1–2 Objectives To convert FACIT-F and SF-36 Bodily Pain (BP) scores to PROMIS Fatigue and PI scores to determine how PROMIS performs in 2 phase 3 baricitinib (bari) RA trials. Methods In RA-BEAM, pts with inadequate response (IR) to MTX were randomised 3:3:2 to placebo (PBO) once daily (QD), bari-4 mg QD, or adalimumab (ADA) 40 mg biweekly.3 In RA-BEACON, pts with IR to bDMARDs were randomised 1:1:1 to receive PBO or bari 2 mg or 4 mg QD.4 FACIT-F assessed fatigue and SF-36 BP, pain. Pt-level PROMIS scores were converted from FACIT-F/SF-36 BP using validated crosswalk tables.1–2 Analysis of covariance was conducted on PROMIS score conversions to compare bari to all treatment arms. Results Pts had considerable baseline fatigue/pain; mean scores approached or exceeded 1 SD (10 points on the metric) from population norms. Bari was associated with clinically relevant improvements (exceeding 0.5 SD/5 points on the T-score metric) vs PBO for PROMIS fatigue/PI scores (table 1). PROMIS fatigue/PI scores in RA-BEAM reached population norms ( Data are mean (SD) aHigher PROMIS scores mean more fatigue/pain bBEACON was a 24 week study ADA=adalimumab; bari=baricitinib; PBO=placebo Conclusions While PROMIS was not used in the studies directly, pt-level crosswalk tables provide an estimate of effect that may be demonstrated when using PROMIS in clinical trials. These results provide preliminary evidence of the ability of PROMIS to demonstrate treatment benefit. References [1] Lai et al. J Pain Symptom Manage 2014;48:639–48. [2] Cook et al. Qual Life Res 2015;24:2305–18. [3] Taylor, et al. NEJM 2017;376:652–62. [4] Genovese, et al. NEJM 2016;374:1243–52. Disclosure of Interest C. Bingham III Grant/research support from: BMS, Consultant for: Eli Lilly and Company, Janssen, Pfizer, UCB, BMS, Sanofi/Regeneron, C. Gaich Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, A. DeLozier Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, A. Quebe Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, L. Sun Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, S. Otawa Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, J. Pope Grant/research support from: Amgen, Bayer, BMS, GSK, Merck, Novartis, Pfizer, Roche, UCB, Consultant for: AbbVie, Amgen, Bayer, BMS, Celtrion, Lilly, Merck, Novartis, Pfizer, Roche, UCB

Background In patients (pts) with RA, physical function (PF) can be measured with the Health Assessment Questionnaire-Disability Index (HAQ-DI). Patient-Reported Outcomes Measurement Information System (PROMIS) was developed by the National Institutes of Health using a population-calibrated T-score metric (Mean 50, SD 10). Crosswalk tables that link legacy instruments to PROMIS instruments, including PF, have been developed. Comparisons to the general population can also be made from PROMIS scores.1–2 Objectives To convert HAQ-DI scores to PROMIS PF scores to determine how the PROMIS metric performs in 2 phase 3 baricitinib (bari) clinical trials in pts with RA. Methods In RA-BEAM, pts with inadequate response (IR) to methotrexate were randomised 3:3:2 to placebo (PBO) once daily (QD), bari 4 mg QD, or adalimumab (ADA) 40 mg biweekly.3 In RA-BEACON, pts with IR to bDMARDs were randomised 1:1:1 to receive PBO or bari 2 mg or 4 mg QD.4 In both studies, PF was assessed using HAQ-DI. Patient-level HAQ-DI scores were converted to PROMIS PF scores using a validated crosswalk table.1 Analysis of covariance was conducted on the PROMIS PF score conversions to compare bari to all treatment arms in both studies. Missing data were imputed using modified last observation carried forward. Results Pts had considerable PF impairment at baseline; mean scores exceeded 2 SD (20 points on the T-score metric) from population means (table 1). Treatment with bari was associated with clinically relevant improvements approaching or exceeding 0.5 SD (5 points on the T-score metric) by week 24 (minimally important difference for PROMIS PF: 0.2 SD or 2 points5) vs PBO in HAQ-DI converted to PROMIS PF scores (table 1). Using the converted PROMIS scores, bari remained associated with significant improvements in PF vs PBO through 24 weeks in both studies and vs ADA through 52 weeks in RA-BEAM (figure 1). Conclusions While RA-BEAM and RA-BEACON did not use the PROMIS instrument directly, these results indicate PROMIS PF has the potential to show responsiveness and differentiate between active treatments in clinical trials. References [1] Schalet, et al. J Gen Intern Med2015;30:1517–23; [2] Cook, et al. Qual Life Res2015;24:2305–18. [3] Taylor, et al. NEJM2017;376:652–62. [4] Genovese, et al. NEJM2016;374:1243–52. [5] Hays, et al. Ann Rheum Dis2015;74:104–7. Disclosure of Interest C. Bingham III Grant/research support from: BMS, Consultant for: Eli Lilly and Company, Janssen, Pfizer, UCB, BMS, Sanofi/Regeneron, C. Gaich Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, A. DeLozier Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, A. Quebe Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, L. Sun Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, S. Otawa Employee of: Eli Lilly and Company, J. Pope Grant/research support from: Amgen, Bayer, BMS, GSK, Merck, Novartis, Pfizer, Roche, UCB, Consultant for: AbbVie, Amgen, Bayer, BMS, Celtrion, Lilly, Merck, Novartis, Pfizer, Roche, UCB