Background: Chronic cough and phlegm are frequently reported chronic obstructive pulmonary disease (COPD) symptoms. Prior research classified chronic mucus hypersecretion (CMH) based on the presence of these symptoms for ≥3 months, called chronic bronchitis (CB) if respiratory infection symptoms were present for 1-2 years (Medical Research Council [MRC] definition). We explored whether the COPD Assessment Test (CAT), a simple measure developed for routine clinical use, captures CMH populations and outcomes similarly to MRC and St. George's Respiratory Questionnaire (SGRQ) definitions. Methods: We identified CMH in the SPIROMICS COPD cohort using (a) MRC definitions, (b) SGRQ questions for cough and phlegm (both as most/several days a week), and (c) CAT cough and phlegm questions. We determined optimal cut-points for CAT items and described exacerbation frequencies for different CMH definitions. Moderate exacerbations required a new prescription for antibiotics/oral corticosteroids or emergency department visit; severe exacerbations required hospitalization. Results were stratified by smoking status. Results: In a population of 1431 participants (57% male; mean FEV 1 % predicted 61%), 47% and 49% of evaluable participants had SGRQ-or CAT-defined CMH, respectively. A cut-point of ≥2 for cough and phlegm items defined CMH in CAT. Among SGRQ-CMH+ participants, 80% were also defined as CMH+ by the CAT. CMH+ participants were more likely to be current smokers. A higher exacerbation frequency was observed for presence of CMH+ versus CMH− in the year prior to baseline for all CMH definitions; this trend continued across 3 years of follow-up, regardless of smoking status. Conclusion: Items from the CAT identified SGRQ-defined CMH, a frequent COPD trait that correlated with exacerbation frequency. The CAT is a short, simple questionnaire and a potentially valuable tool for telemedicine or real-world trials. CAT-based CMH is a novel approach for identifying clinically important characteristics in COPD that can be ascertained in these settings.

BackgroundInhaled corticosteroids (ICS) are the primary treatment for persistent asthma. Currently available ICS have differing particle size due to both formulation and propellant, and it has been postulated that this may impact patient outcomes. This structured literature review and meta-analysis compared the effect of small and standard particle size ICS on lung function, symptoms, rescue use (when available) and safety in patients with asthma as assessed in head-to-head randomized controlled trials (RCTs).MethodsA systematic literature search of MEDLINE was performed to identify RCTs (1998–2014) evaluating standard size (fluticasone propionate-containing medications) versus small particle size ICS medication in adults and children with asthma. Efficacy outcomes included forced expiratory volume in 1 s (FEV1), morning peak expiratory flow (PEF), symptom scores, % predicted forced expiratory flow between 25 and 75% of forced vital capacity (FEF25–75%), and rescue medication use. Safety outcomes were also evaluated when available.ResultsTwenty-three independent trials that met the eligibility criteria were identified. Benefit-risk plots did not demonstrate any clinically meaningful differences across the five efficacy endpoints considered and no appreciable differences were noted for most safety endpoints. Meta-analysis results, using a random-effects model, demonstrated no significant difference between standard and small size particle ICS medications in terms of effects on mean change from baseline FEV1 (L) (−0.011, 95% confidence interval [CI]: −0.037, 0.014 [N = 3524]), morning PEF (L/min) (medium/low doses: −3.874, 95% CI: −10.915, 3.166 [N = 1911]; high/high-medium doses: 5.551, 95% CI: −1.948, 13.049 [N = 749]) and FEF25–75% predicted (−2.418, 95% CI: −6.400; 1.564 [N = 115]).ConclusionsBased on the available literature, no clinically significant differences in efficacy or safety were observed comparing small and standard particle size ICS medications for the treatment of asthma.Trial registrationGSK Clinical Study Register No: 202012.

Introduction Ixekizumab, a selective interleukin-17A antagonist, was compared with adalimumab in the SPIRIT-H2H study (NCT03151551) in patients with psoriatic arthritis (PsA) and concomitant psoriasis. This post hoc analysis reports outcomes to week 52 in patients from SPIRIT-H2H, stratified by baseline psoriasis severity. Methods SPIRIT-H2H was a 52-week, multicenter, randomized, open-label, rater-blinded, parallel-group study of biologic disease-modifying antirheumatic drug (DMARD)-naïve patients ( N = 566) with PsA and active psoriasis (≥ 3% body surface area involvement). Patients were randomized to ixekizumab or adalimumab (1:1) with stratification by baseline concomitant use of conventional synthetic DMARDs and psoriasis severity (with/without moderate-to-severe psoriasis). Patients received on-label dosing according to psoriasis severity. The primary endpoint was the proportion of patients simultaneously achieving ≥ 50% improvement in American College of Rheumatology criteria (ACR50) and 100% improvement in Psoriasis Area Severity Index (PASI100) at week 24. Secondary endpoints included musculoskeletal, disease activity (defined by composite indices), skin and nail, quality of life and safety outcomes. In this post hoc analysis, primary and secondary endpoints of SPIRIT-H2H were analyzed by baseline psoriasis severity. Results A greater proportion of patients achieved the combined endpoint of ACR50 + PASI100 and PASI100 with ixekizumab compared with adalimumab at weeks 24 and 52, regardless of baseline psoriasis severity. ACR response rates were similar for ixekizumab and adalimumab across both patient subgroups. For musculoskeletal outcomes, similar efficacy was seen for ixekizumab and adalimumab, but ixekizumab showed greater responses for skin outcomes regardless of psoriasis severity. The safety profiles of ixekizumab and adalimumab were consistent between subgroups. Conclusions Regardless of baseline psoriasis severity, ixekizumab demonstrated greater efficacy than adalimumab with respect to simultaneous achievement of ACR50 + PASI100, and showed consistent and sustained efficacy across PsA-related domains. It also demonstrated higher response rates for skin outcomes. These subgroup analyses highlight the efficacy of ixekizumab in patients with PsA irrespective of the severity of concomitant psoriasis. Supplementary Information The online version contains supplementary material available at 10.1007/s40744-021-00388-8.

Purpose Understanding risk factors for an acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is important for optimizing patient care. We re-analyzed data from the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) study (NCT00292552) to identify factors predictive of re-exacerbations and associated with prolonged AECOPDs. Methods Patients with COPD from ECLIPSE with moderate/severe AECOPDs were included. The end of the first exacerbation was the index date. Timing of re-exacerbation risk was assessed in patients with 180 days’ post-index-date follow-up data. Factors predictive of early (1–90 days) vs late (91–180 days) vs no re-exacerbation were identified using a multivariable partial-proportional-odds-predictive model. Explanatory logistic-regression modeling identified factors associated with prolonged AECOPDs. Results Of the 1,554 eligible patients from ECLIPSE, 1,420 had 180 days’ follow-up data: more patients experienced early (30.9%) than late (18.7%) re-exacerbations; 50.4% had no re-exacerbation within 180 days. Lower post-bronchodilator FEV 1 ( P =0.0019), a higher number of moderate/severe exacerbations on/before index date ( P <0.0001), higher St. George’s Respiratory Questionnaire total score ( P =0.0036), and season of index exacerbation (autumn vs winter, P =0.00164) were identified as predictors of early (vs late/none) re-exacerbation risk within 180 days. Similarly, these were all predictors of any (vs none) re-exacerbation risk within 180 days. Median moderate/severe AECOPD duration was 12 days; 22.7% of patients experienced a prolonged AECOPD. The odds of experiencing a prolonged AECOPD were greater for severe vs moderate AECOPDs (adjusted odds ratio=1.917, P =0.002) and lower for spring vs winter AECOPDs (adjusted odds ratio=0.578, P =0.017). Conclusion Prior exacerbation history, reduced lung function, poorer respiratory-related quality-of-life (greater disease burden), and season may help identify patients who will re-exacerbate within 90 days of an AECOPD. Severe AECOPDs and winter AECOPDs are likely to be prolonged and may require close monitoring.

Nail psoriasis is a chronic, difficult-to-treat condition affecting almost half of patients with psoriasis. It is associated with considerable social stigma and impairment of patients’ quality of life. The aim of this study was to assess improvements in objective measures of nail psoriasis, among patients from the long-term extension of the UNCOVER-3 study who received the interleukin-17A inhibitor ixekizumab and had either nail psoriasis (Nail Psoriasis Severity Index (NAPSI) ≥ 1) or significant nail psoriasis (fingernail NAPSI ≥ 16 and ≥ 4 fingernails involved) at baseline. Efficacy outcomes reported through week 264 included the mean percentage improvements from baseline in NAPSI score and the proportion of patients achieving nail psoriasis resolution (NAPSI=0). In UNCOVER-3, 56.9% (219/385) of patients had nail psoriasis at baseline; of those, 61.2% (134/219) had significant nail psoriasis. At week 60, a total of 66.9% and 59.1% of patients with baseline nail psoriasis and significant baseline nail psoriasis, respectively, reported complete clearance of nail psoriasis, an effect which was sustained through week 264. This analysis demonstrates that continuous treatment with ixekizumab in adult patients with moderate-to-severe-psoriasis during 264 weeks was associated with improvements and clearance of fingernail psoriasis, irrespective of the severity of nail psoriasis at baseline.