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Alopecia areata (AA) is a CD8+ T cell–mediated autoimmune disease characterized by nonscarring hair loss. Ivarmacitinib, which is a selective oral Janus kinase 1 inhibitor, may interrupt certain cytokine signaling implicated in the pathogenesis of AA. To evaluate the efficacy and safety of ivarmacitinib in adult patients with AA who have ≥25% scalp hair loss. Eligible patients were randomized 1:1:1:1 to receive ivarmacitinib 2, 4, or 8 mg once daily or placebo for 24 weeks. The primary end point was the percentage change from baseline in the Severity of Alopecia Tool score at week 24. A total of 94 patients were randomized. At week 24, the least squares mean difference in the percentage change from baseline in the Severity of Alopecia Tool score for ivarmacitinib 2, 4, and 8 mg and placebo groups were −30.51% (90% CI, −45.25, −15.76), −56.11% (90% CI, −70.28, −41.95), −51.01% (90% CI, −65.20, −36.82), and −19.87% (90% CI, −33.99, −5.75), respectively. Two serious adverse events—follicular lymphoma and COVID-19 pneumonia—were reported. A small sample size limits the generalizability of the results. Treatment with ivarmacitinib 4 and 8 mg doses in patients with moderate and severe AA for 24 weeks was efficacious and generally tolerated. [ABSTRACT FROM AUTHOR]

Malignancy risk surveillance among patients receiving long-term immunomodulatory psoriasis treatments remains an important safety objective. To report malignancy rates in patients with moderate-to-severe psoriasis treated with guselkumab for up to 5 years versus general and psoriasis patient populations. Cumulative rates of malignancies/100 patient-years (PY) were evaluated in 1721 guselkumab-treated patients from VOYAGE 1 and 2. Malignancy rates (excluding nonmelanoma skin cancer [NMSC]) were compared with rates in the Psoriasis Longitudinal Assessment and Registry. Standardized incidence ratios comparing malignancy rates (excluding NMSC and cervical cancer in situ) between guselkumab-treated patients and the general US population using Surveillance, Epidemiology, and End Results data were calculated, adjusting for age, sex, and race. Of 1721 guselkumab-treated patients (>7100 PY), 24 had NMSC (0.34/100PY; basal:squamous cell carcinoma ratio, 2.2:1), and 32 had malignancies excluding NMSC (0.45/100PY). For comparison, the malignancy rate excluding NMSC was 0.68/100PY in the Psoriasis Longitudinal Assessment and Registry. Malignancy rates (excluding NMSC/cervical cancer in situ) in guselkumab-treated patients were consistent with those expected in the general US population (standardized incidence ratio = 0.93). Inherent imprecision in determining malignancy rates. In patients treated with guselkumab for up to 5 years, malignancy rates were low and generally consistent with rates in general and psoriasis patient populations. [ABSTRACT FROM AUTHOR]

Deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 inhibitor, inhibits cytokine signaling in psoriasis pathogenesis. The objective of this study was to demonstrate deucravacitinib superiority versus placebo and apremilast in moderate to severe plaque psoriasis based on ≥75% reduction from baseline in Psoriasis Area and Severity Index and a static Physician's Global Assessment score of 0 (clear) or 1 (almost clear) with a ≥2-point improvement from baseline at week 16. POETYK psoriasis second trial (NCT03611751), a 52-week, double-blinded, phase 3 trial, randomized patients 2:1:1 to deucravacitinib 6 mg every day (n = 511), placebo (n = 255), or apremilast 30 mg twice a day (n = 254). At week 16, significantly more deucravacitinib-treated patients versus placebo and apremilast patients achieved ≥75% reduction from baseline in Psoriasis Area and Severity Index (53.0% vs 9.4% and 39.8%; P <.0001 vs placebo; P =.0004 vs apremilast) and static Physician's Global Assessment score of 0 or 1 (49.5% vs 8.6% and 33.9%; P <.0001 for both). Efficacy was maintained until week 52 with continuous deucravacitinib. The most frequent adverse event with deucravacitinib was nasopharyngitis. Serious adverse events and discontinuations due to adverse events were infrequent. No clinically meaningful changes were observed in laboratory parameters. The study duration was 1 year. Deucravacitinib demonstrated superiority versus placebo and apremilast and was well tolerated in adults with moderate to severe plaque psoriasis. [ABSTRACT FROM AUTHOR]

Background: Long-term maintenance treatment is required for patients with psoriasis.Objectives: To evaluate the efficacy and safety of guselkumab in patients with moderate to severe psoriasis through 3 years of treatment.Methods: In 2 ongoing, phase 3 trials of guselkumab (VOYAGE 1 and VOYAGE 2), the proportions of patients achieving at least 90% and 100% improvement in the Psoriasis Area and Severity Index (PASI 90 and PASI 100, respectively) and Investigator's Global Assessment (IGA) scores of 0/1 and 0 were summarized for the guselkumab group (including placebo-to-guselkumab crossover). Patients who met treatment failure rules were considered nonresponders. Safety outcomes (rates/100 patient-years [PY]) were evaluated based on data pooled across studies through week 156.Results: Three-year response rates for the guselkumab group in VOYAGE 1 and VOYAGE 2, respectively, were 82.8% and 77.2% for PASI 90, 50.8% and 48.8% for PASI 100, 82.1% and 83.0% for IGA score of 0/1, and 53.1% and 52.9% for IGA score of 0. Safety event rates across studies occurred through week 156 as follows: serious adverse events, 5.68/100 PY; serious infections, 1.15/100 PY; nonmelanoma skin cancers, 0.28/100 PY; malignancies other than nonmelanoma skin cancer, 0.47/100 PY; and major adverse cardiovascular events, 0.28/100 PY. Week 156 and week 100 rates were consistent.Limitations: There was no comparator arm beyond 1 year.Conclusions: Guselkumab shows durable efficacy and a consistent safety profile in patients with moderate to severe psoriasis treated for up to 3 years. [ABSTRACT FROM AUTHOR]

Background: Significant unmet need exists for long-term treatment of moderate to severe atopic dermatitis (AD).Objective: To assess the long-term safety and efficacy of dupilumab in patients with AD.Methods: This ongoing, multicenter, open-label extension study (NCT01949311) evaluated long-term dupilumab treatment in adults who had previously participated in phase 1 through 3 clinical trials of dupilumab for AD. This analysis examined patients given 300 mg dupilumab weekly for up to 76 weeks at data cutoff (April 2016). Safety was the primary outcome; efficacy was also evaluated.Results: Of 1491 enrolled patients (1042.9 patient-years), 92.9% were receiving treatment at cutoff. The safety profile was consistent with previously reported trials (420.4 adverse events/100 patient-years and 8.5 serious adverse events/100 patient-years), with no new safety signals; common adverse events included nasopharyngitis, conjunctivitis, and injection-site reactions. Sustained improvement was seen up to 76 weeks in all efficacy outcomes, including measures of skin inflammation, pruritus, and quality of life.Limitations: Lack of control arm, limited number of patients with 76 weeks or longer of treatment (median follow-up, 24 weeks), and patients not receiving the approved dose regimen of 300 mg every 2 weeks.Conclusion: The safety and efficacy profile from this study supports the role of dupilumab as continuous long-term treatment for patients with moderate to severe AD. [ABSTRACT FROM AUTHOR]

Background: ABP 501 is a biosimilar of adalimumab.Objective: We sought to compare the efficacy and safety of ABP 501 with adalimumab.Methods: This 52-week, double-blind study randomized patients with moderate to severe psoriasis to ABP 501 or adalimumab. At week 16, those with 50% or more improvement in Psoriasis Area and Severity Index score from baseline on ABP 501 continued the same treatment, whereas adalimumab-treated patients were rerandomized to adalimumab or ABP 501. Clinical similarity in Psoriasis Area and Severity Index percent improvement from baseline to week 16 (primary end point) was established if the point estimate of treatment difference and its 2-sided 95% confidence interval between groups was within equivalence margin of ±15. Patients, including those undergoing a single transition at week 16, were evaluated for safety and immunogenicity.Results: Psoriasis Area and Severity Index percent improvement at week 16 was 80.9 for ABP 501 and 83.1 for adalimumab (least-square mean difference -2.18 [95% confidence interval -7.39 to 3.02]). Adverse events (67.2% [117/174] vs 63.6% [110/173]) and antidrug antibody incidence (55.2% [96/174] vs 63.6% [110/173]) for ABP 501 vs adalimumab were similar. Safety, including immunogenicity, was similar among groups after single transition (week 20).Limitations: The 52-week data are not reported here.Conclusions: ABP 501 was shown to be clinically similar to adalimumab. Safety and immunogenicity were not impacted immediately after single transition (adalimumab to ABP 501). [ABSTRACT FROM AUTHOR]

Background: Phase II data suggested that guselkumab, an anti-interleukin-23 monoclonal antibody, was efficacious in psoriasis.Objective: We sought to assess efficacy and safety of guselkumab in moderate to severe psoriasis versus placebo and adalimumab, including interrupted treatment and switching adalimumab nonresponders to guselkumab.Methods: Patients were randomized to guselkumab 100 mg (weeks 0 and 4, then every 8 weeks; n = 496); placebo→guselkumab (weeks 0, 4, and 12 then guselkumab at weeks 16 and 20; n = 248); or adalimumab (80 mg week 0, then 40 mg week 1, and every 2 weeks through week 23; n = 248). At week 28, guselkumab 90% or greater improvement in Psoriasis Area and Severity Index (PASI) score from baseline (PASI 90) responders were rerandomized to guselkumab or placebo with guselkumab after loss of response. Placebo→guselkumab responders and adalimumab responders received placebo, then guselkumab after loss of response. Nonresponders received guselkumab.Results: At week 16, more patients receiving guselkumab achieved an Investigator Global Assessment (IGA) score 0/1 (cleared/minimal) (84.1% vs 8.5%) and PASI 90 (70.0% vs 2.4%) versus placebo (coprimary end points). Guselkumab was superior to adalimumab at week 16 (IGA score 0/1, 75% or greater improvement in PASI score from baseline, and PASI 90) and week 24 (IGA score 0/1 and 0, PASI 90, 100% improvement in PASI score from baseline) (P < .001). From weeks 28 to 48, better persistence of response was observed in guselkumab maintenance versus withdrawal groups (P < .001). Of adalimumab nonresponders who switched to guselkumab, 66.1% achieved PASI 90 at week 48. Guselkumab improved patient-reported outcomes. Adverse events were comparable among groups.Limitations: One-year follow-up limits retreatment data.Conclusions: Guselkumab is a highly effective, well-tolerated, maintenance therapy, including in adalimumab nonresponders. [ABSTRACT FROM AUTHOR]

• Fatigue severity in MS linked to a range of variables including depression. • Overlap between fatigue and tiredness as depressive symptom complicates interpretation. • Network analysis of large early RRMS cohort including structural MRI of brain. • No link between fatigue severity and cognitive performance, or included MRI metrics. • Fatigue linked to individual depressive symptoms in addition to tiredness. Fatigue is common and disabling in multiple sclerosis (MS), yet its mechanisms are poorly understood. In particular, overlap in measures of fatigue and depression complicates interpretation. We applied a multivariate network approach to quantify relationships between fatigue and other variables in early MS. Data were collected from patients with newly diagnosed immunotherapy-naïve relapsing-remitting MS at baseline and month 12 follow-up in FutureMS, a Scottish nationally representative cohort. Subjective fatigue was assessed by Fatigue Severity Scale. Detailed phenotyping included measures assessing each of physical disability, affective disorders, cognitive performance, sleep quality, and structural brain imaging. Network analysis was conducted to estimate partial correlations between variables. Baseline networks were compared between those with persistent and remitted fatigue at one-year follow up. Data from 322 participants at baseline, and 323 at month 12, were included. At baseline, 154 patients (47.8%) reported clinically significant fatigue. In the network analysis, fatigue severity showed strongest connections with depression, followed by Expanded Disability Status Scale. Conversely, fatigue severity was not linked to objective cognitive performance or brain imaging variables. Even after controlling for measurement of "tiredness" in our measure of depression, four specific depressive symptoms remained linked to fatigue. Results were consistent at baseline and month 12. Overall network strength was not significantly different between groups with persistent and remitted fatigue (4.89 vs 2.90, p = 0.11). Our findings support robust links between subjective fatigue and depression in early relapsing-remitting MS. Shared mechanisms between specific depressive symptoms and fatigue could be key targets of treatment and research in MS-related fatigue. [ABSTRACT FROM AUTHOR]

• Pre-specified analyses of neuropathic pain in MS SMART randomised controlled trial. • We analyzed 445 participants with secondary progressive multiple sclerosis. • Study agents Fluoxetine, riluzole and amiloride compared separately to placebo. • No benefit of trial agents was observed in any neuropathic pain outcome measure. • No benefit of trial agents in overall pain, nor perceived impact of pain. Evidence-based treatment of pain in people with MS presents a major unmet need. We aimed to establish if use of Fluoxetine, Riluzole or Amiloride improved neuropathic pain outcomes in comparison to placebo, in adults with secondary progressive MS participating in a trial of these putative neuroprotectants. In pre-specified secondary analyses of the MS SMART phase-2b double-blind randomised controlled trial (NCT01910259), we analyzed reports of neuropathic pain, overall pain, and pain interference. Multivariate analyses included adjustment for baseline pain severity. Additionally, we explored associations of pain severity with clinical and MRI brain imaging variables. 445 Participants were recruited from 13 UK neuroscience centres. We found no statistically significant benefit of active intervention on any rating of neuropathic pain, or pain overall. Compared to placebo, adjusted mean difference in pain intensity was 0.38 (positive values favouring placebo, 95%CI -0.30 to 1.07, p = 0.27) for Amiloride; 0.52 (-0.17 to 1.22, p = 0.14) for Fluoxetine; and 0.40 (-0.30 to 1.10, p = 0.26) for Riluzole. Pain severity was positively correlated with depressive symptoms (Spearman correlation 0.19, 95%CI 0.10–0.28) and fatigue (Rho 0.30, 95%CI 0.20–0.39). Use of Fluoxetine, Riluzole or Amiloride was not associated with improvement in neuropathic pain symptoms, in comparison to placebo. [ABSTRACT FROM AUTHOR]

• Hidden disability is present in most newly diagnosed people with multiple sclerosis. • 26% of participants improve in hidden disability burden one year after diagnosis. • Fingolimod and cladribine are associated with improvement in a small subgroup. • Overall disease modifying therapy has no substantial impact on hidden disability. In addition to motor disability, "hidden disability" such as depression, anxiety, fatigue, sleep disturbance, cognitive impairment and pain is a major complaint of people with multiple sclerosis. We explored changes in hidden disability burden in the early post-diagnostic period and examined the hypothesis that disease modifying therapies have a beneficial effect on hidden disability burden. Adults with recently diagnosed (< 6 months) relapsing-remitting multiple sclerosis (n = 440, mean age 37.4 ± 10.4, 76% female), from a national multicentre cohort study (FutureMS) underwent testing with clinical and neuropsychological instruments as well as brain MRI at baseline and after 12-months. Disease modifying therapies were only started after baseline assessment and were classified into injectables (n = 70, interferons, glatiramer acetate), other DMTs (n = 215) and no DMT (n = 117, reference). Sensitivity analyses were undertaken using alternative classifications (disease modifying therapy vs none, and a 3-category system). We performed latent transition analysis with hidden disability burden as the latent variable including propensity score weights. We identified three classes with low (58%), moderate (25%) and high (17%) hidden disability burden. 70% did not transition ("unchanged", reference), 26% transitioned into a lower burden class ("improvement") and 4% transitioned into a higher burden class ("worsening"). Median treatment duration was 11 months (IQR 9–12). Injectables [OR 1.3 (95%CIs 0.7, 2.3); P = 0.4] and other DMTs [OR 1.4 (95%CIs 0.9, 2.1); P = 0.2] were not associated with significant change in hidden disability burden in either direction ("improvement" or "worsening"). In the alternative 3-category classification, category 2 treatment (fingolimod, cladribine, n = 22) was associated with improvement [OR 4.3 (2.6, 7.0); P < 0.001]. Hidden disability was present in most newly diagnosed people with multiple sclerosis. The majority remained unchanged and approximately a quarter improved over the immediate post-diagnostic period. Disease modifying therapy had no significant influence on hidden disability burden in the study period of one year following diagnosis. The trend towards favourable outcomes with fingolimod and cladribine should be interpreted with caution due to the small sample size. Our exploratory data are observational, with scope for attendant biases, but highlight the need for further study including longer-term evaluation as well as randomised trials for non-motor disability. [ABSTRACT FROM AUTHOR]

Background: Established endovascular treatments for aortic dissection often result in incomplete aortic repair, potentially leading to late complications involving the distal aorta. To address the problems of incomplete true lumen reconstitution and late aneurysmal change, we report the midterm results of combined proximal endografting with distal true lumen bare-metal stenting (STABLE: Staged Total Aortic and Branch vesseL Endovascular reconstruction) in Stanford type A and B aortic dissection. Methods: Between January 2003 and January 2010, 31 patients underwent staged total aortic and branch vessel endovascular reconstruction for management of acute (type A, 13; type B, 11) and chronic (type B, 7) aortic dissection. Proximal endografting was combined with bare-metal Z stent implantation in the distal true lumen. Patients with type A dissection underwent adjunctive treatment at operation. Computed tomography angiography was performed at baseline, 1 year, and annually thereafter to assess aortic remodelling. Results: Primary technical success was 97%. Thirty-day rates of death, stroke, and permanent paraplegia/paresis were 3% (n = 1), 0%, and 0%, respectively. Mean follow-up was 57.3 months (range, 5 to 100 months). Overall survival was 60% at 100 months. Aortic-specific survival was 93%. Four patients (13%) underwent device-related reintervention. One (3%) late aortic-related death occurred. Thoracic (p = 0.64) and abdominal (p = 0.14) aortic dimensions were stable. The true lumen index increased significantly at follow-up. Conclusions: Staged total aortic and branch vessel endovascular reconstruction is a feasible ancillary endovascular technique to address the problems of distal true lumen collapse, incomplete aortic remodelling, and late aneurysm formation in aortic dissection. [ABSTRACT FROM AUTHOR]

Topical photodynamic therapy (PDT) is used to treat nonmelanoma skin cancers, such as actinic keratoses, Bowen''s disease, and basal cell carcinoma (superficial and nodular). This article presents up-to-date, practical, evidence-based recommendations on the use of topical PDT using 5-aminolevulinic acid or methyl aminolevulinate for the treatment (and prevention) of nonmelanoma skin cancers. A systematic literature review was conducted (using MEDLINE), and recommendations were made on the basis of the quality of evidence for efficacy, safety/tolerability, cosmetic outcome, and patient satisfaction/preference. Topical PDT is highly effective in the treatment of actinic keratoses, Bowen''s disease, superficial and thin nodular basal cell carcinomas, with cosmesis typically superior to that achieved with existing standard therapies. PDT may also be a means of preventing certain nonmelanoma skin cancers in immunosuppressed patients. [Copyright &y& Elsevier]

Background The optimal long-term dosing strategy for adalimumab (ADA) in hidradenitis suppurativa/acne inversa (HS) was evaluated by pooling the results of the PIONEER phase 3 trials and an open-label extension (OLE) study. Objective To assess the response to and tolerability of long-term administration of ADA in HS. Methods The durations of the PIONEER I/II periods A, B, and OLE were 12, 24, and 52 or more weeks, respectively. Patients who entered the OLE and received ADA (40 mg every week continuously) and responders plus partial responders (PRRs) were evaluated. Primary efficacy assessments included measurement of HS clinical response (HiSCR), lesion counts, skin pain, and Dermatology Life Quality Index (DLQI). Treatment-emergent adverse events were assessed. Results At week 12, 52.3% of those receiving ADA weekly and 73.0% of PRRs achieved HiSCR. Achievement of HiSCR was maintained through week 168 in 52.3% of patients who received ADA weekly and 57.1% of PRRs. Sustained improvement in lesion counts, skin pain, and DLQI score were also observed. The safety profile throughout the OLE was similar to the profiles observed in the PIONEER studies. Limitations The OLE was uncontrolled. Conclusion Continuous weekly dosing with ADA, 40 mg, is a reasonable treatment option for long-term control of moderate-to-severe HS. Graphical abstract [ABSTRACT FROM AUTHOR]

Background: The optimal long-term dosing strategy for adalimumab (ADA) in hidradenitis suppurativa/acne inversa (HS) was evaluated by pooling the results of the PIONEER phase 3 trials and an open-label extension (OLE) study.Objective: To assess the response to and tolerability of long-term administration of ADA in HS.Methods: The durations of the PIONEER I/II periods A, B, and OLE were 12, 24, and 52 or more weeks, respectively. Patients who entered the OLE and received ADA (40 mg every week continuously) and responders plus partial responders (PRRs) were evaluated. Primary efficacy assessments included measurement of HS clinical response (HiSCR), lesion counts, skin pain, and Dermatology Life Quality Index (DLQI). Treatment-emergent adverse events were assessed.Results: At week 12, 52.3% of those receiving ADA weekly and 73.0% of PRRs achieved HiSCR. Achievement of HiSCR was maintained through week 168 in 52.3% of patients who received ADA weekly and 57.1% of PRRs. Sustained improvement in lesion counts, skin pain, and DLQI score were also observed. The safety profile throughout the OLE was similar to the profiles observed in the PIONEER studies.Limitations: The OLE was uncontrolled.Conclusion: Continuous weekly dosing with ADA, 40 mg, is a reasonable treatment option for long-term control of moderate-to-severe HS. [ABSTRACT FROM AUTHOR]

Psoriasis and psoriatic arthritis are common conditions for which treatment options have until recently been extremely limited. Recent advances in our understanding of the immunology and genetics underlying these conditions have been rapid, and have contributed to the development of new therapies for these diseases. This article discusses the current state of the art in our understanding of the aetiopathogenesis of psoriasis and psoriatic arthritis, and current therapies for the diseases. [Copyright &y& Elsevier]

The article offers information about Interleukin-17 (IL-17), which has been emerged as an important factor in the pathogenesis of psoriasis. It states that AMG 827, a human monoclonal antibody, binds with human IL-17 receptor antagonist (IL-17RA) and prevents the biological activity of IL-17 antagonists. It also presents several charts and graphs which shows that single doses of AMG 827 lead to rapid improvement in psoriasis area and severity index (PASI) responses.

Abstract: The oblique projection is used widely in imaging of the lower vascular tree. Much of the evidence justifying the oblique projection is anecdotal. This study compares the sensitivity of the anteroposterior (AP) projection alone in lower limb vascular catheter angiography to that combined with the oblique projection. 110 digitally subtracted angiograms were analysed initially on AP and subsequently on oblique views. Oblique imaging increases confidence, demonstrates stenoses not seen on AP and changes the diagnosis. This supports the use of the oblique projection in lower limb vascular interventional imaging. [ABSTRACT FROM AUTHOR]

Abstract: Interventional radiology is continuing to reshape current practice in many specialties of clinical care. It is a relatively new and innovative branch of medicine in which physicians treat diseases non-operatively through small catheters guided to the target by fluoroscopic and other imaging modalities. The aim is to provide image-guided, minimally invasive alternatives to traditional surgical and medical procedures in suitable cohorts of patients. Procedures which previously required major surgery can now be performed by interventional radiologists, sometimes on an outpatient basis, with little patient discomfort. In this review, we highlight the importance of interventional radiology in treating a comprehensive range of obstetric and gynaecological pathologies. [Copyright &y& Elsevier]