Navitas Systems (United States)

By combining perspective materials processing techniques, device engineering, and circuit integration methods, this special edition provides a comprehensive overview of the state of the art in SiC-based power electronics device fabrication technologies, serving as a valuable resource for researchers, engineers, and practitioners in the field.

Psoriasis body surface area (BSA) of 10% or more has been a major criterion for determining systemic therapy eligibility. However, patients with BSA < 10% and even ≤ 3% may have high disease burden and difficulties accessing biologics. To assess psoriasis burden among patients with BSA ≤ 10%, this study characterized patient-reported outcomes (PROs) across BSA categories among systemic treatment-naïve patients initiating biologic therapy. Patients from the CorEvitas Psoriasis Registry initiating biologics between April 2015 and September 2023 were categorized according to low (< 3%), medium (3-10%), or high (> 10%) BSA involvement. Measures assessed at initiation of biologic therapy included health-related quality of life, itch, pain, fatigue, psoriatic arthritis, psoriasis disease characteristics, and medical history. Overlap between BSA groups for each outcome was calculated via non-parametric Mann-Whitney statistic transformation (range 0.0-1.0; 0.5 indicates complete similarity [i.e., for a comparison between low and high BSA groups, overlap of 0.5 means there is 50% probability that a randomly selected patient with low BSA would have the same or greater PRO burden as one with high BSA]; 0 or 1 indicates complete dissimilarity) to determine whether each measure differed in randomly selected patients with low or medium versus high BSA. Of 1640 patients who initiated biologics, 7.0% had low BSA, 46.9% had medium BSA, and 46.2% had high BSA involvement. PRO overlap statistics ranged from 0.52 to 0.59 and from 0.60 to 0.70 for randomly selected patients with high versus medium and low BSA, respectively, indicating patients with high and medium BSA are likely to have similar levels of disease burden, and patients with high BSA are slightly more likely to have higher disease burden than those with low BSA. Near complete overlap (range 0.44-0.58) was observed for psoriasis disease characteristics and medical history in thelow versus high and medium BSA groups. Observed overlap in PROs across BSA categories shows that patients with low BSA can experience similarly poor quality of life and high symptom burden to those with higher BSA. These findings support the appropriateness of considering biologic therapies for patients with low BSA and indicators of high disease burden. ClinicalTrials.gov: NCT02707341.

Provide clinical whole genome sequencing (WGS) and genetic counseling to a diverse and international population of people living with Parkinson’s disease (PD).

ObjectivesTo compare effectiveness of tofacitinib versus tumor necrosis factor inhibitors (TNFi), and across tofacitinib lines of therapy, in patients with rheumatoid arthritis (RA), using US CorEvitas RA Registry data.MethodsAnalysis included patients with RA initiating tofacitinib or TNFi with a 12-month follow-up visit between November 2012–February 2021. Primary (Clinical Disease Activity Index-defined low disease activity [CDAI-LDA: CDAI ≤ 10]) and secondary (clinical/disease activity/patient-reported) effectiveness outcomes were assessed at month 12. Outcomes were stratified by treatment regimen (overall tofacitinib vs overall TNFi/tofacitinib monotherapy vs tofacitinib combination therapy/TNFi monotherapy vs TNFi combination therapy/tofacitinib monotherapy vs TNFi combination therapy/tofacitinib combination therapy vs TNFi combination therapy), or tofacitinib line of therapy (2nd/3rd/ ≥ 4th line).Results3,481 eligible patients initiated tofacitinib (n = 805) or TNFi (n = 2,676). Improvements in effectiveness at month 12 were generally similar across treatment regimens; 25.1% and 30.1% of overall tofacitinib and TNFi initiators achieved CDAI-LDA, respectively (odds ratio 1.29 [95% confidence interval (CI) 0.94, 1.76]). Odds ratios (95% CIs) for achieving CDAI-LDA at 12 months were 0.70 (0.36, 1.37) for 3rd- versus 2nd-line, and 1.09 (0.63, 1.88) for 3rd- versus ≥ 4th-line tofacitinib initiators. At month 12, mean change from baseline in CDAI was greater among 3rd- versus ≥ 4th-line tofacitinib initiators, and mean Health Assessment Questionnaire and patient-reported pain were greater in 3rd- versus 2nd-line and ≥ 4th- versus 3rd-line tofacitinib initiators.ConclusionsGenerally, there were no differences in effectiveness between tofacitinib versus TNFi regimens. Few differences were observed between tofacitinib lines of therapy; sample sizes were small for 2nd/3rd-line initiators.Study registrationNCT01402661 (ClinicalTrials.gov; July 25, 2011).Key Points• Using data from the US CorEvitas rheumatoid arthritis (RA) Registry, this study compared the effectiveness of tofacitinib versus tumor necrosis factor inhibitors (TNFi) and across tofacitinib lines of therapy.• Effectiveness of tofacitinib was similar to TNFi regimens up to month 12, while differences in some effectiveness outcomes at month 12 were observed with tofacitinib across different lines of therapy.• The findings of this study may inform future treatment decision-making in patients with RA.

BackgroundThe International Psoriasis Council (IPC) updated the classification of psoriasis severity to guide clinical decision-making. According to IPC guidelines, patients are considered candidates for systemic therapy when body surface area (BSA) is >10%, when lesions affect special body areas (ie, face, palms, soles, genitals, scalp, or nails), or when topical therapy fails to control symptoms.ObjectiveTo evaluate patient candidacy for systemic therapy in real-world settings, according to disease severity criteria.MethodsThis cross-sectional study included systemic treatment-naive patients from the CorEvitas Psoriasis Registry who initiated systemic treatment at Registry visits between April 2015 and April 2023. Based on IPC criteria, systemic therapy candidates were identified, and data on demographics and clinical characteristics, including disease severity indicators (ie, BSA and Psoriasis Area Severity Index [PASI] scores) and patient-reported outcome measures, were collected and descriptively summarized.ResultsThe analysis included 2739 systemic therapy initiators with plaque psoriasis, of whom 82.7% met IPC criteria for systemic therapy. Of the 2265 systemic therapy candidates, 56.2% had a BSA >10%, 53.2% had a history of psoriasis affecting special areas, and 55.2% had prior but not current use of topical therapy. Notably, 71.0% of candidates for systemic therapy had PASI scores ≤12.ConclusionIn this large real-world study, most patients with psoriasis who initiated systemic therapy met the IPC disease severity criteria to do so. Disease severity categorization based on PASI scores and BSA percentage alone may not adequately capture all patients who might be candidates for systemic psoriasis treatment.Clinicaltrials.govNCT02707341.

Abstract Introduction/Background Tralokinumab is a high-affinity monoclonal antibody that specifically targets IL-13, a driver of inflammation in atopic dermatitis (AD). The ECZTRA 1, 2, 3, and 6 trials demonstrated that tralokinumab is efficacious and safe in adults and adolescents; however, real-world evidence on tralokinumab use is limited. Objectives To assess the change from baseline in clinician-assessed and patient-reported outcomes (PROs) among US adults with AD following 6 months of persistent tralokinumab use after treatment initiation in the CorEvitas AD registry. Methods The CorEvitas AD Registry is a prospective, non-interventional registry launched in July 2020 for adult AD patients under the care of a licensed dermatologist or qualified dermatology practitioner. This analysis includes US patients enrolled in the CorEvitas AD registry who initiated tralokinumab between February 1, 2022 and May 31, 2023, had baseline data, and were persistent on tralokinumab at the 6-month follow-up (defined as a visit occurring 5 to 9 months from tralokinumab initiation). Baseline data were summarized using descriptive statistics and stratified by advanced systemic therapy (AST) experience (defined as any previous history of dupilumab, abrocitinib, or upadacitinib). Outcome measures collected included: validated Investigator’s Global Assessment for atopic dermatitis (vIGA-ADTM), ≥50%/≥75% improvement in Eczema Area and Severity Index (EASI) (EASI-50/75), ≥4-point improvement in Dermatology Life Quality Index (DLQI), ≥3-point improvement in mean weekly pruritis numerical rating scale, and mean change in Work Productivity and Activity Impairment (WPAI). Results Among the 60 patients in this analysis, the mean age was 49.1 years and mean AD duration was 15.0 years. The majority of patients were female (34/60, 56.7%), White (51/60, 85.0%), worked full-time (38/60, 63.3%), and AST-naïve (44/60, 73.3%). At baseline, the majority of patients had moderate-to-severe AD based on EASI (EASI≥ 7, 40/60, 67%) and vIGA-ADTM (vIGA-ADTM 3: 50/60, 83.3%; vIGA-ADTM 4: 4/60, 6.7%). Disease severity was lower in AST-experienced patients, all of whom were dupilumab-experienced. A notable proportion of patients experienced improvements in clinician-assessed endpoints and PROs from baseline to 6 months: vIGA-ADTM ≤1 from 6.7% (4/60) to 55.0% (33/60), EASI ≤7 from 33.3% (20/60) to 85.0% (51/60), and DLQI ≤5 from 38.3% (23/60) to 66.7% (40/60). Among patients with EASI ≥7.1 at baseline, 85.0% (34/40) achieved EASI-50 (AST-naïve: 90.9%, 30/33; AST-experienced: 57.1%, 4/7) and 77.5% (31/40) achieved EASI-75 (AST-naïve: 84.8%, 28/33; AST-experienced: 42.9%, 3/7) at the 6-month follow-up. In patients with vIGA-ADTM of 3 or 4 at baseline, 79.6% (43/54) achieved EASI-50 (AST-naïve: 83.3%, 35/42; AST-experienced: 66.7%, 8/12) and 66.7% (36/54) achieved EASI-75 (AST-naïve: 76.2%, 32/42; AST-experienced: 33.3%, 4/12) at follow-up. Among patients with baseline DLQI ≥4, 71.4% (30/42) achieved ≥4-point improvement at follow-up (AST-naïve: 78.1%, 25/32; AST-experienced: 50.0%, 5/10). Of patients with baseline mean weekly pruritus NRS ≥3, 69.8% (37/53) achieved ≥3-point improvement at follow-up (AST-naïve: 70.0%, 28/40; AST-experienced: 69.2%, 9/13). Among the 40 patients employed at both baseline and follow-up visit, improvements were reported in WPAI. Percent impairment at work due to AD decreased by 14.8% (95% CI: -25.6%; -3.9%) and percent overall work impairment due to AD decreased by 15.7% (95% CI: -26.4%; -5.0%). For all 60 patients, non-work activity impairment due to AD decreased by 14.5% (95% CI: -23.9%; -5.1%). Conclusions In this real-world study, patients with AD experienced notable improvements in both clinician-assessed and patient-reported outcomes after 6-months of persistent tralokinumab treatment, regardless of prior AST therapy use. All 16 AST-experienced patients had prior use of dupilumab. These findings support the therapeutic potential of tralokinumab for AD patients, highlighting the need for future studies with longer follow-up period and larger sample size.

Fabry Registry data were analyzed among 83 agalsidase beta-treated patients with Fabry disease who switched to migalastat. Outcomes (estimated glomerular filtration rate [eGFR], urine protein-creatinine ratio [UPCR], plasma globotriaosylceramide [GL-3], plasma globotriaosylsphingosine [lyso-GL-3], interventricular septal wall thickness [IVST], left posterior wall thickness [LPWT], left ventricular mass index [LVMI]) were assessed using linear mixed models to estimate annual change over time in the pre- and postswitch periods. eGFR decreased throughout both periods (preswitch: -0.85 mL/min/1.73 m2/year; postswitch: -1.96 mL/min/1.73 m2/year; both p < 0.0001), with steeper decline postswitch (ppre/post = 0.01) in both classic and late-onset patients. UPCR increased significantly postswitch (ppre/post = 0.003) among classic patients and was stable in both periods among late-onset patients. GL-3 trajectories worsened postswitch across phenotypes (ppre/post = 0.0005 classic, 0.02 late-onset). LPWT was stable preswitch (0.07 mm/year, p = 0.25) and decreased postswitch (-0.51 mm/year, p = 0.0005; ppre/post = 0.0009), primarily among late-onset patients. IVST and LVMI slopes varied significantly by phenotype. Among classic patients, IVST and LVMI were stable and decreasing, respectively preswitch and increasing postswitch (ppre/post = 0.02 IVST, 0.01 LVMI). Among late-onset patients, IVST significantly decreased postswitch (ppre/post = 0.0003); LVMI was stable over time (ppre/post = 0.89). Ultimately, eGFR and GL-3 trajectories worsened postswitch across phenotypes, while UPCR and cardiac measures worsened among classic and stabilized/improved among late-onset patients. These findings indicate variability in long-term outcomes after switching from ERT to migalastat, underscoring the importance of careful monitoring.

BackgroundChronic respiratory insufficiency from progressive muscle weakness causes morbidity and mortality in late-onset Pompe disease (LOPD). Previous Pompe Registry (NCT00231400) analyses for ≤ 5 years’ alglucosidase alfa treatment showed a single linear time trend of stable forced vital capacity (FVC) % predicted.MethodsTo assess longer term Pompe Registry data, piecewise linear mixed model regression analyses estimated FVC% predicted trajectories in invasive-ventilator-free patients with LOPD aged ≥ 5 years. We estimated annual FVC change 0–6 months, > 6 months–5 years, and > 5–13 years from treatment initiation, adjusting for baseline age, sex, and non-invasive ventilation.FindingsAmong 485 patients (4612 FVC measurements; 8.3 years median follow-up), median ages at symptom onset, diagnosis, and alglucosidase alfa initiation were 34.3, 41.1, and 44.9 years, respectively. FVC% increased during the first 6 months’ treatment (slope 1.83%/year; 95% confidence interval: 0.66, 3.01; P = 0.0023), then modestly declined −0.54%/year (−0.79, −0.30; P < 0.0001) during > 6 months–5 years, and −1.00%/year (−1.36, −0.63; P < 0.0001) during > 5–13 years. The latter two periods’ slopes were not significantly different from each other (Pdifference = 0.0654) and were less steep than published natural history slopes (−1% to −4.6%/year). Estimated individual slopes were ≥ 0%/year in 96.1%, 30.3%, and 13.2% of patients during the 0–6 month, > 6 month–5 year, and > 5–13 year periods, respectively.ConclusionThese real-world data indicate an alglucosidase alfa benefit on FVC trajectory that persists at least 13 years compared with published natural history data. Nevertheless, unmet need remains since most individuals demonstrate lung function decline 5 years after initiating treatment. Whether altered FVC trajectory impacts respiratory failure incidence remains undetermined.Trial registrationThis study was registered (NCT00231400) on ClinicalTrials.gov on September 30, 2005, retrospectively registered.