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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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Baricitinib previously demonstrated improvements in itch and sleep disturbance versus placebo in adults with moderate-to-severe atopic dermatitis (AD). Examine if itch and sleep improvements are associated with better quality of life (QoL) and productivity in patients with AD. 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. 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%). Patients with AD who experienced itch and sleep improvement had significantly better QoL and productivity. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: To assess the measurement properties of two single-item patient-reported outcome (PRO) measures that assessed the length of time (in minutes) and severity of morning joint stiffness (MJS) experienced each day.Methods: Data from two Phase 3, randomized placebo-controlled (and active-controlled [RA-BEAM]), clinical studies assessing the safety and efficacy of baricitinib in adults with moderately to severely active rheumatoid arthritis (RA) were used to evaluate the psychometric properties of the Duration of MJS and Severity of MJS PROs.Results: Test-retest reliability of Duration of MJS and Severity of MJS was supported through large intraclass correlation coefficients among stable patients (coefficient range for both studies: 0.88 to 0.93). In support of construct validity, moderate correlations were evidenced between Duration of MJS and other related patient- and clinician-reported assessments of RA symptoms and patient functioning, whereas moderate-to-strong correlations were evidenced between these same patient- and clinician-reported assessments and Severity of MJS. Statistically significant differences between the median and mean values of Duration of MJS and Severity of MJS for differing categories of RA disease severity supported known-groups validity. Finally, large and statistically significant differences in change scores from Day 1 to Week 12 for patients defined as responders versus non-responders using the American College of Rheumatology 20 criteria supported the responsiveness of both PROs.Conclusion: Duration of MJS and Severity of MJS PROs demonstrated reliability, validity, and responsiveness in adults with moderately to severely active RA, supporting the measurement of these key symptoms in clinical trials. [ABSTRACT FROM AUTHOR]

Background: To assess the reliability, validity, and responsiveness to treatment change of the single-item measure, Severity of Worst Tiredness, in patients with rheumatoid arthritis (RA).Methods: Data from two Phase 3, randomized, placebo-controlled (RA-BUILD; and active-controlled [RA-BEAM]), clinical studies of the efficacy of baricitinib in adults with moderately to severely active RA were used. The psychometric properties of the single-item measure, Severity of Worst Tiredness, were assessed, including test-retest reliability, convergent and discriminant validity, known-groups validity, and responsiveness, using other patient- and clinician-reported outcomes frequently assessed in RA patients.Results: Test-retest reliability of the Severity of Worst Tiredness was supported through large intraclass correlation coefficients (0.89 ≤ ICC ≤ 0.91). Moderate-to-large correlations were observed between this patient-reported outcome (PRO) and other related patient- and clinician-reported assessments of RA symptoms and patient functioning, supporting construct validity of the measure (│r│ ≥ 0.41). The instrument also displayed known-groups validity through statistically significant differences between mean values of the Severity of Worst Tiredness defined using other indicators of RA severity. Finally, responsiveness was supported by large and statistically significant differences in change scores from Day 1 to Week 12 for patients comparing responders and nonresponders using the American College of Rheumatology 20 (ACR20) criteria.Conclusion: The Severity of Worst Tiredness PRO demonstrated adequate reliability, validity, and responsiveness in clinical trials of adults with moderately to severely active RA and is fit for purpose in this patient population. [ABSTRACT FROM AUTHOR]

Background and Objective: People with type 2 diabetes mellitus (T2DM) often interrupt basal insulin treatment soon after initiation. This study aimed to describe the experiences during and after basal insulin initiation among people with T2DM with different persistence patterns.Methods: Adults with T2DM from France, Germany, Spain, UK, US, Brazil, and Japan were identified from consumer panels for an online survey. Respondents who initiated basal insulin 3-24 months prior to survey date were categorized as continuers (no gaps of ≥7 days in insulin treatment); interrupters (first gap ≥7 days within 6 months of initiation and restarted insulin); and discontinuers (stopped insulin for ≥7 days within 6 months of initiation without restarting).Results: Among 942 participants, continuers were older than interrupters and discontinuers (46, 37, and 38 years, respectively, p < .01). Continuers reported having fewer concerns before and after insulin initiation than interrupters and discontinuers, while interrupters had the most concerns. Continuers also reported fewer challenges during the first week of insulin use. Continuers were more likely to respond that insulin use had a positive impact on specific aspects of life than interrupters and discontinuers, for example on glycemic control (73.0%, 63.0%, and 61.8%, respectively; p < .01 vs. continuers).Conclusion: Among people with T2DM with different persistence patterns after basal insulin initiation there were significant differences in patient characteristics and experience during and after insulin initiation. Interrupters and discontinuers more frequently reported having concerns and challenges during the initiation process, negative impacts after initiation, and less improvement in glycemic control than continuers. [ABSTRACT FROM AUTHOR]

Background: Initiation and titration of human regular U-500 insulin (U-500R) with a dosing algorithm of either thrice daily (TID) or twice daily (BID) improved glycemic control with fewer injections in patients with type 2 diabetes treated with high-dose, high-volume U-100 insulin. The objective of this analysis was to compare patient-reported outcomes between U-500R TID and BID treatment groups in this titration-to-target randomized, clinical trial. Methods: In this 24-week, open-label, parallel trial, 325 patients were randomized to TID (n = 162) or BID (n = 163) U-500R after a 4-week lead-in period (screening). The Treatment Related Impact Measure-Diabetes (TRIM-D) and EQ-5D-5L questionnaires were administered at screening, baseline/randomization, and endpoint (24 weeks). The Visual Analog Scale-Injection Site Pain (VAS-ISP) was assessed at baseline/randomization, 12 weeks, and endpoint. Results: The TRIM-D showed statistically significant improvements in overall scores from baseline to endpoint for both BID and TID groups, most domains in the TID group, and all domains in the BID group. The BID group achieved better scores than the TID patients in overall and in treatment burden, daily life, and compliance domains (p < .05). EQ-5D-5L index scores showed no statistically significant differences for TID and BID groups (and no differences between TID and BID groups) from baseline to endpoint. VAS-ISP scores improved for both treatment groups (-5.60 TID; -6.47 BID; p < .05 for both) from baseline to endpoint. Conclusions: U500 can be successfully titrated for improved glycemic control using BID and TID regimens with diabetes-specific Patient-Reported Outcomes showing improvements in both arms; however, BID had better scores than TID in overall, treatment burden, daily life, and compliance domains. [ABSTRACT FROM AUTHOR]

Objectives: To assess baricitinib on patient-reported outcomes (PROs) in patients with moderately to severely active rheumatoid arthritis, who had insufficient response or intolerance to ≥1 tumour necrosis factor inhibitors (TNFis) or other biological disease-modifying antirheumatic drugs (bDMARDs).Methods: In this double-blind phase III study, patients were randomised to once-daily placebo or baricitinib 2 or 4 mg for 24 weeks. PROs included the Short Form-36, EuroQol 5-D, 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, duration of morning joint stiffness (MJS) and Work Productivity and Activity Impairment Questionnaire-Rheumatoid Arthritis. Treatment comparisons were performed with logistic regression for categorical measures or analysis of covariance for continuous variables.Results: 527 patients were randomised (placebo, 176; baricitinib 2 mg, 174; baricitinib 4 mg, 177). Both baricitinib-treated groups showed statistically significant improvements versus placebo in most PROs. Improvements were generally more rapid and of greater magnitude for patients receiving baricitinib 4 mg than 2 mg and were maintained to week 24. At week 24, more baricitinib-treated patients versus placebo-treated patients reported normal physical functioning (HAQ-DI <0.5; p≤0.001), reductions in fatigue (FACIT-F ≥3.56; p≤0.05), improvements in PtGA (p≤0.001) and pain (p≤0.001) and reductions in duration of MJS (p<0.01).Conclusions: Baricitinib improved most PROs through 24 weeks compared with placebo in this study of treatment-refractory patients with previously inadequate responses to bDMARDs, including at least one TNFi. PRO results aligned with clinical efficacy data for baricitinib.Trial Registration Number: NCT01721044; Results. [ABSTRACT FROM AUTHOR]

Background: The Impact of Weight on Self-Perceptions Questionnaire (IW-SP) assesses an individual's self-perception related to his or her weight. The primary objective of this study was to provide evidence of the reliability, validity, and responsiveness of the IW-SP. Materials and Methods: Study participants were individuals with type 2 diabetes mellitus (T2DM) and obesity enrolled in clinical weight-loss programs in the United States. Data were obtained for clinical measures, IW-SP, and other patient-reported outcome measures. An intraclass correlation coefficient (ICC) and Cronbach's α were calculated for test-retest reliability and internal consistency, respectively. For validity, correlations and t tests were performed. For responsiveness, baseline and 6-month data for a subgroup of patients were analyzed using the paired t test and calculation of effect size (ES). Results: Reliability data for 106 study participants (mean age, 52 years; 69% female; 31% white; mean body mass index, 38 kg/m2) yielded an ICC of 0.85 and Cronbach's α values of >0.89. IW-SP scores were associated with obesity-related quality of life, mental health, and vitality ( r>0.50, P<0.001). In the subgroup ( n=40) used to estimate responsiveness, weight was significantly less at end point than at baseline (mean, baseline=231.9 vs. end point=222.0 pounds; P<0.001; ES=0.23), and IW-SP scores were significantly better than at baseline (mean, baseline=61.0 vs. end point=72.1 [on a scale of 0-100]; P=0.01; ES=0.34). Mean IW-SP change scores significantly discriminated between those achieving >5% body weight loss and those who achieved <5% (mean change, 23.6 vs. 5.7; P=0.03). Conclusions: The IW-SP has demonstrated reliability, validity, and responsiveness in individuals with T2DM and obesity, thereby making it a potentially valuable tool in the evaluation of weight-loss interventions targeted toward patients with T2DM. [ABSTRACT FROM AUTHOR]

Background Baricitinib, an oral selective inhibitor of Janus kinase 1 and Janus kinase 2, modulates proinflammatory cytokine signaling. Objectives The efficacy and safety of baricitinib were evaluated in patients with moderate-to-severe atopic dermatitis (AD). Methods In this phase 2, randomized, double-blind, placebo-controlled study, 124 patients with moderate-to-severe AD applied topical corticosteroids (TCSs) for 4 weeks before randomization to once-daily placebo, 2 mg of baricitinib, or 4 mg of baricitinib for 16 weeks. Use of TCSs was permitted during the study. The primary outcome was the proportion of patients achieving at least a 50% reduction in the Eczema Area and Severity Index (EASI-50) compared with placebo. Results Significantly more patients who received baricitinib, 4 mg, achieved EASI-50 than did patients receiving placebo (61% vs 37% [ P =.027]) at 16 weeks. The difference between the proportion of patients receiving baricitinib, 2 or 4 mg, who achieved EASI-50 and the proportion of patients receiving placebo and achieving EASI-50 was significant as early as week 4. Baricitinib also improved pruritus and sleep loss. Treatment-emergent adverse events were reported in 24 of the patients receiving placebo (49%), 17 of those receiving 2 mg of baricitinib (46%), and 27 of those receiving 4 mg of baricitinib (71%). Limitations A TCS standardization period before randomization reduced disease severity, limiting the ability to compare results with those of baricitinib monotherapy. Longer studies are required to confirm baricitinib's efficacy and safety in patients with AD. Conclusions Baricitinib used with TCSs reduced inflammation and pruritus in patients with moderate-to-severe AD. [ABSTRACT FROM AUTHOR]

Background: Baricitinib, an oral selective inhibitor of Janus kinase 1 and Janus kinase 2, modulates proinflammatory cytokine signaling.Objectives: The efficacy and safety of baricitinib were evaluated in patients with moderate-to-severe atopic dermatitis (AD).Methods: In this phase 2, randomized, double-blind, placebo-controlled study, 124 patients with moderate-to-severe AD applied topical corticosteroids (TCSs) for 4 weeks before randomization to once-daily placebo, 2 mg of baricitinib, or 4 mg of baricitinib for 16 weeks. Use of TCSs was permitted during the study. The primary outcome was the proportion of patients achieving at least a 50% reduction in the Eczema Area and Severity Index (EASI-50) compared with placebo.Results: Significantly more patients who received baricitinib, 4 mg, achieved EASI-50 than did patients receiving placebo (61% vs 37% [P = .027]) at 16 weeks. The difference between the proportion of patients receiving baricitinib, 2 or 4 mg, who achieved EASI-50 and the proportion of patients receiving placebo and achieving EASI-50 was significant as early as week 4. Baricitinib also improved pruritus and sleep loss. Treatment-emergent adverse events were reported in 24 of the patients receiving placebo (49%), 17 of those receiving 2 mg of baricitinib (46%), and 27 of those receiving 4 mg of baricitinib (71%).Limitations: A TCS standardization period before randomization reduced disease severity, limiting the ability to compare results with those of baricitinib monotherapy. Longer studies are required to confirm baricitinib's efficacy and safety in patients with AD.Conclusions: Baricitinib used with TCSs reduced inflammation and pruritus in patients with moderate-to-severe AD. [ABSTRACT FROM AUTHOR]

Background: Initiation and titration of human regular U-500 insulin (U-500R) with a dosing algorithm of either thrice daily (TID) or twice daily (BID) improved glycemic control with fewer injections in patients with type 2 diabetes treated with high-dose, high-volume U-100 insulin. The objective of this analysis was to compare patient-reported outcomes between U-500R TID and BID treatment groups in this titration-to-target randomized, clinical trial. Methods: In this 24-week, open-label, parallel trial, 325 patients were randomized to TID (n = 162) or BID (n = 163) U-500R after a 4-week lead-in period (screening). The Treatment Related Impact Measure-Diabetes (TRIM-D) and EQ-5D-5L questionnaires were administered at screening, baseline/randomization, and endpoint (24 weeks). The Visual Analog Scale-Injection Site Pain (VAS-ISP) was assessed at baseline/randomization, 12 weeks, and endpoint. Results: The TRIM-D showed statistically significant improvements in overall scores from baseline to endpoint for both BID and TID groups, most domains in the TID group, and all domains in the BID group. The BID group achieved better scores than the TID patients in overall and in treatment burden, daily life, and compliance domains (p < .05). EQ-5D-5L index scores showed no statistically significant differences for TID and BID groups (and no differences between TID and BID groups) from baseline to endpoint. VAS-ISP scores improved for both treatment groups (-5.60 TID; -6.47 BID; p < .05 for both) from baseline to endpoint. Conclusions: U500 can be successfully titrated for improved glycemic control using BID and TID regimens with diabetes-specific Patient-Reported Outcomes showing improvements in both arms; however, BID had better scores than TID in overall, treatment burden, daily life, and compliance domains. Trial Registration: These secondary analyses are based on the study first received January 22, 2013 and reported in Clinical Trial Registry No.: NCT01774968 . [ABSTRACT FROM AUTHOR]

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.). [ABSTRACT FROM AUTHOR]

Background: Patients with systemic lupus erythematosus have substantial unmet medical need. Baricitinib is an oral selective Janus kinase (JAK)1 and JAK2 inhibitor that we hypothesised might have therapeutic benefit in patients with systemic lupus erythematosus.Methods: In this double-blind, multicentre, randomised, placebo-controlled, 24-week phase 2 study, patients were recruited from 78 centres in 11 countries. Eligible patients were aged 18 years or older, had a diagnosis of systemic lupus erythematosus, and had active disease involving skin or joints. We randomly assigned patients (1:1:1) to receive once-daily baricitinib 2 mg, baricitinib 4 mg, or placebo for 24 weeks. The primary endpoint was the proportion of patients achieving resolution of arthritis or rash at week 24, as defined by Systemic Lupus Erythematosus Disease Activity Index-2000 (SLEDAI-2K). Efficacy and safety analyses included all patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, number NCT02708095.Findings: Between March 24, 2016, and April 27, 2017, 314 patients were randomly assigned to receive placebo (n=105), baricitinib 2 mg (n=105), or baricitinib 4 mg (n=104). At week 24, resolution of SLEDAI-2K arthritis or rash was achieved by 70 (67%) of 104 patients receiving baricitinib 4 mg (odds ratio [OR] vs placebo 1·8, 95% CI 1·0-3·3; p=0·0414) and 61 (58%) of 105 patients receiving baricitinib 2 mg (OR 1·3, 0·7-2·3; p=0·39). Adverse events were reported in 68 (65%) patients in the placebo group, 75 (71%) patients in the baricitinib 2 mg group, and 76 (73%) patients in the baricitinib 4 mg group. Serious adverse events were reported in ten (10%) patients receiving baricitinib 4 mg, 11 (10%) receiving baricitinib 2 mg, and five (5%) receiving placebo; no deaths were reported. Serious infections were reported in six (6%) patients with baricitinib 4 mg, two (2%) with baricitinib 2 mg, and one (1%) with placebo.Interpretation: The baricitinib 4 mg dose, but not the 2 mg dose, significantly improved the signs and symptoms of active systemic lupus erythematosus in patients who were not adequately controlled despite standard of care therapy, with a safety profile consistent with previous studies of baricitinib. This study provides the foundation for future phase 3 trials of JAK1/2 inhibition with baricitinib as a new potential oral therapy for systemic lupus erythematosus.Funding: Eli Lilly and Company. [ABSTRACT FROM AUTHOR]

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., Competing Interests: Competing interests: Dr YMFA has received research funding from Kgl Hofbundtmager Aage Bang Foundation and AP Moller Foundation. Ms. LN has nothing to declare. Dr RTB, Mrs. AMD and Mrs. EE-H are employees and stockholders of Eli Lilly and Company. Dr AE has received research funding from Pfizer, Eli Lilly, Novartis, Bristol-Myers Squibb, AbbVie, Janssen Pharmaceuticals, the Danish National Psoriasis Foundation, the Simon Spies Foundation and the Kgl Hofbundtmager Aage Bang Foundation and honoraria as consultant and/or speaker from AbbVie, Almirall, Leo Pharma, Galápagos NV, Sun Pharmaceuticals, Samsung Bioepis, Ltd, Pfizer, Eli Lilly and Company, Novartis, Galderma, Dermavant, UCB, Mylan, Bristol-Myers Squibb and Janssen Pharmaceuticals., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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., Competing Interests: Conflicts of interest Dr King reports serving on advisory boards and/or is a consultant and/or is a clinical trial investigator for Aclaris Therapeutics Inc, Almirall, Arena Pharmaceuticals, Bioniz Therapeutics, Bristol-Meyers Squibb, Concert Pharmaceuticals Inc, Dermavant Sciences Inc, Eli Lilly and Company, Incyte Corp, Pfizer Inc, TWi Biotechnology Inc, and Viela Bio and is on speaker bureaus for Pfizer Inc, Regeneron, and Sanofi Genzyme. Dr Mesinkovska reports receiving honoraria and/or fees from Eli Lilly and Company outside the submitted work, serving as chief scientific officer for the National Alopecia Areata Foundation, and serves on advisory boards for Arena Pharmaceuticals, Concert Pharmaceuticals, Eli Lilly and Company, and Nutrafol. Dr Craiglow reports receiving honoraria and/or fees from Eli Lilly and Company outside the submitted work, Aclaris Therapeutics Inc, Arena Pharmaceuticals Inc, Pfizer Inc, Regeneron Pharmaceuticals Inc, and Sanofi Genzyme. Dr Kindred reports receiving honoraria and/or fees from Eli Lilly and Company outside the submitted work, serves on advisory boards for Eli Lilly and Company and UCB, is a speaker for Selphyl and Aerolase, and is the Chair of the National Medical Association, Dermatology Section. Dr Ko serves on advisory boards and is a consultant and clinical investigator for Eli Lilly and Company, and he has served as a clinical investigator and/or consultant for AbbVie, Sanofi, Regeneron, Dermira, BMS, and Arena Pharmaceuticals and has received consulting fees from Eli Lilly and Company, Concert Pharmaceuticals, and Arena Pharmaceuticals outside the submitted work. Dr McMichael reports receiving honoraria and/or fees from Eli Lilly and Company outside the submitted work, serving as a consultant for Eli Lilly and Company, and Pfizer Inc, and as a researcher for Concert Pharmaceuticals. Dr Shapiro reports serving as a consultant for Eli Lilly and Company, as a consultant and investigator for Pfizer Inc, and has received honoraria from Pfizer Inc, Eli Lilly and Company, Applied Biology, and DS Laboratories outside the submitted work, and served as an investigator for RegenLab and received stock options for Eirion and Replicel Life Sciences. Dr Mirmirani reports acting as a Principal Investigator, clinical trials for Concert Pharmaceuticals, Eli Lilly and Company, and Pfizer Inc, is a compensated consultant/advisory board member for Eli Lilly and Company, and a consultant for DS Laboratories, Monat Global, Almirall, Thirty Madison, Leo Pharmaceuticals, Bristol Myers Squibb, P&G. Dr Hordinsky reports being an investigator for alopecia areata clinical trials sponsored by Pfizer Inc, Eli Lilly and Company, and Concert Pharmaceuticals and being a consultant for CASSIOPEA S.p.A., and the immediate past president of the American Hair Research Society. Dr Huang reports royalty payments to her institution from Pfizer for licensing of the ALTO tool and consulting fees from Concert Pharmaceuticals, Pfizer Inc, and Eli Lilly and Company. Dr Castelo-Soccio reports receiving fees for alopecia-related presentations, participating in a scientific advisory panel for Pfizer Inc and on the medical advisory board for the National Alopecia Areata Foundation. Dr Bergfeld reports personal and other fees from Eli Lilly and Company, Chairing the International Federation of Hair Research, and being a former president of the American Hair Research Society. Dr Paller reports being an investigator for AbbVie, AnaptysBio, Eli Lilly, Incyte, KrystalBio, Janssen, and Regeneron, on a data safety monitoring board for AbbVie and Galderma, and a consultant with honorarium for AbbVie, Abeona, Almirall, Amagma, Anaptysbio, Arena, Bausch, Bristol Myer Squibb, Dermavant, Dermira, Eli Lilly, Exicure, Forte, Leo, Lifemax, Phoenix, Pierre Fabre, Pfizer, Rapt, Regeneron, Sanofi, Sol-Gel, UCB, and Venthera. Dr Mackay-Wiggan reports receiving honoraria and/or fees from Eli Lilly and Company, being a consultant for Pfizer Inc, Eli Lilly and Company, and Concert Pharmaceuticals, and participating in an advisory board for Eli Lilly and Company, and receipt of site-related equipment and consumables from Pfizer Inc and Concert Pharmaceuticals. Dr Glashofer reports serving as a consultant for Eli Lilly and Company. Dr Piliang reports receiving grants/contract for study sites from Pfizer Inc, and Eli Lilly and Company. Dr Lo Sicco reports receiving a grant from Pfizer Education for alopecia areata-related work, and being a RegenLab, and Pfizer Inc. Dr Cassella reports being an employee and stockholder of Concert Pharmaceuticals. Author Koenigsberg reports being an employee and stockholder of Concert Pharmaceuticals. Dr Ghorayeb reports being an employee and stockholder of Janssen Global Services, LLC. Dr Fakharzadeh reports being a current employee and stockholder of Janssen Global Services, LLC. Dr Napatalung reports being a current employee and stockholder of Pfizer Inc. Author Gandhi reports being an employee and stockholder of Pfizer Inc. Dr DeLozier reports being an employee and stockholder at Eli Lilly and Company. Dr Nunes reports being an employee and stockholder at Eli Lilly and Company during manuscript development and being a current employee and stockholder at Janssen Global Services, LLC. Dr Senna reports clinical trial funding and SAB consulting fees from Eli Lilly and Company, during the conduction of the study and reported clinical trial funding from Concert Pharmaceuticals and SAB consulting fees from Pfizer Inc. Drs Tosti, Aguh, and Ahluwalia do not have conflicts of interest to disclose., (Copyright © 2021 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Atopic dermatitis (AD) is a common, chronic, relapsing, inflammatory skin disease causing a variety of dermatologic signs and symptoms, affecting patient&rsquo;s 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.

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 &ldquo;itch-scratch cycle&rdquo;, 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.

Background: Atopic dermatitis (AD) has a negative impact on patients&rsquo; 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&ndash;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&ndash;13 October 2019, Madrid, Spain. Poster number P0233.J Drugs Dermatol. 2020;19(10): 943-948. doi:10.36849/JDD.2020.5422.

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., (Copyright © 2020. Published by Elsevier Inc.)

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., Competing Interests: Conflicts of Interest: All authors are employees or retired employees of Eli Lilly and Company.