Improvement In Skin Disease Research Articles

Validation of Cutaneous Dermatomyositis Disease Area and Severity Index Activity Score and Other Efficacy Outcomes as Measures of Skin Disease in Dermatomyositis in the Lenabasum Phase 3 Trial

In the past decade, there have been six industry-sponsored phase 3 trials in adult patients with dermatomyositis (DM), primarily focusing on improving muscle weakness. However, skin disease is a cardinal manifestation of DM. This study evaluated the sensitivity of Cutaneous Dermatomyositis Disease Area and Severity Index Activity score, Cutaneous Dermatomyositis Activity Investigator Global Assessment, Total Improvement Score, and other outcome measures used in DM clinical trials to detect improvement in DM skin disease activity. Data analyzed from the lenabasum phase 3 trial in DM showed that improvement in Cutaneous Dermatomyositis Disease Area and Severity Index Activity score increased proportionately with the degree of patient- or physician-reported improvement in skin disease, consistently measuring improvement when clinically meaningful improvement was reported at weeks 16-52. In contrast, Cutaneous Dermatomyositis Activity Investigator Global Assessment measured little change from baseline with reported no improvement in skin disease but also a similar change from baseline with slight improvement. No Skindex-29+3 subscale performed well at reflecting increasing degrees of improvement in skin disease. Extramuscular Global Assessment and Total Improvement Score generally showed increasing levels of improvement as the degree of patient- and physician-reported improvement in skin disease increased, but these are composite measures and are not specific to improvement in DM skin disease. To measure clinically meaningful improvement in skin disease in a DM trial, Cutaneous Dermatomyositis Disease Area and Severity Index Activity score is the more sensitive outcome measure across time points.

Efficacy of Integrated Online Mindfulness and Self-compassion Training for Adults With Atopic Dermatitis

Quality of life (QOL) of patients with atopic dermatitis (AD) is reported to be the lowest among skin diseases. To our knowledge, mindfulness and self-compassion training has not been evaluated for adults with AD. To evaluate the efficacy of mindfulness and self-compassion training in improving the QOL for adults with AD. This randomized clinical trial conducted from March 2019 through October 2022 included adults with AD whose Dermatology Life Quality Index (DLQI) score, a skin disease-specific QOL measure, was greater than 6 (corresponding to moderate or greater impairment). Participants were recruited from multiple outpatient institutes in Japan and through the study's social media outlets and website. Participants were randomized 1:1 to receive eight 90-minute weekly group sessions of online mindfulness and self-compassion training or to a waiting list. Both groups were allowed to receive any dermatologic treatment except dupilumab. The primary outcome was the change in the DLQI score from baseline to week 13. Secondary outcomes included eczema severity, itch- and scratching-related visual analog scales, self-compassion and all of its subscales, mindfulness, psychological symptoms, and participants' adherence to dermatologist-advised treatments. The study randomized 107 adults to the intervention group (n = 56) or the waiting list (n = 51). The overall participant mean (SD) age was 36.3 (10.5) years, 85 (79.4%) were women, and the mean (SD) AD duration was 26.6 (11.7) years. Among participants from the intervention group, 55 (98.2%) attended 6 or more of the 8 sessions, and 105 of all participants (98.1%) completed the assessment at 13 weeks. The intervention group demonstrated greater improvement in the DLQI score at 13 weeks (between-group difference estimate, -6.34; 95% CI, -8.27 to -4.41; P < .001). The standardized effect size (Cohen d) at 13 weeks was -1.06 (95% CI, -1.39 to -0.74). All secondary outcomes showed greater improvements in the intervention group than in the waiting list group. In this randomized clinical trial of adults with AD, integrated online mindfulness and self-compassion training in addition to usual care resulted in greater improvement in skin disease-specific QOL and other patient-reported outcomes, including eczema severity. These findings suggest that mindfulness and self-compassion training is an effective treatment option for adults with AD. https://umin.ac.jp/ctr Identifier: UMIN000036277.

Preliminary definition of cutaneous flare in dermatomyositis: A retrospective review

To the Editor: The Cutaneous Dermatomyositis Disease Activity and Severity Index (CDASI) is a reliable, validated outcome measure that correlates with quality of life and disease progression.1 Whereas a decrease in activity score correlates well with an improvement in skin disease, the CDASI activity (CDASI-A) score has not been used to quantitatively measure a significant increase in skin activity or a cutaneous flare.

Sleep Apnea and Skin.

Skin disease is associated with obstructive sleep apnea (OSA) both epidemiologically and mechanistically. In this review we highlight conditions which have a well-established link to obstructive sleep apnea, such as psoriasis and atopic dermatitis. We describe putative mechanistic links between OSA and skin disease involving inflammatory pathways, obesity, mechanical upper airways obstruction, and hypoxia. In the context of these mechanisms we describe specific skin conditions, and other conditions which are associated with both skin manifestations (including hair/nail findings) and OSA. The risks/ benefits of CPAP in the context of skin disease are also reviewed. We conclude that further research is needed to understand the mechanisms behind the associations between OSA and skin disease. Given the frequent co-occurrence of OSA and skin conditions, there would be great benefit for OSA clinical trials to consider improvement in skin disease as an outcome measure.

CHRONIC ECZEMA MANAGED WITH AYURVEDIC TREATMENT - A CASE STUDY

Background: Atopic dermatitis, also known as atopic eczema, is a chronic inflammatory skin condition characterized by pruritic, erythematous, and scaly skin lesions often localized to the flexural surfaces of the body. A genetic defect in the filaggrin protein is thought to cause atopic dermatitis by disrupting the ep-idermis. This disruption, in turn, results in contact between immune cells in the dermis and antigens from the external environment leading to intense itching, scratching, and inflammation. Scratching can then lead to further disruption and inflammation of the epidermal skin barrier; this has been described as the itch scratch cycle. According to Ayurveda, it is Raktapradoshajavikara, in which Tridosha are involved, with dominance of Kapha. The management available in current mainstream medicine is unsatisfactory; Various Ayurvedic treatments have been in use for these manifestations. Case Presentation: A 55 years old female patient presented with complaints of itching in both legs, some-times in elbows, patches in both legs since 4 years. She has also known case of HTN since 10 years. Management &amp; Outcome: Patient was admitted in Vasant Prabha Ayurvedic Hospital and was put on Ayurvedic treatment that consisted of whole body Abhyanga, Bashpaswedana, rectal drug administration (Niruhbasti) and other medicaments. She stayed for 30 days in the hospital. This case highlights the im-portance of Ayurvedic treatment in providing fast improvement in skin disease. What benefits the lady could not get in last four years have been achieved by her in just 30 days.

Anti-acne vulgaris effect including skin barrier improvement and 5\u03b1-reductase inhibition by tellimagrandin I from Carpinus tschonoskii

BackgroundCarpinus tschonoskii (CT) has been previously studied for various activities in the improvement of skin diseases. In the present study, we examined the in vitro anti-acne vulgaris (AV) effect of CT leaves (CTL) and tellimagrandin I (TI), one of the main ellagitannins from CT, including skin barrier improvement and 5α-reductase inhibitory activity.MethodsTo test the anti-AV activities of CTL and TI, firstly, anti-oxidative and anti-inflammatory activities including DPPH radical scavenging activity, nitric oxide (NO) inhibitory activity, and cytokines [interleukin (IL)-6 and IL-8] were tested. Skin barrier improvement experiments were tested using developing cornified envelope (CE) formation, and filaggrin mRNA expression level was determined by RT-PCR. The 5α-reductase inhibitory activity was determined by measuring the testosterone levels in rat liver microsomes.ResultsCTL and TI showed potent anti-oxidative activity and anti-inflammatory activities. Especially, the cytokine production inhibitory activities of TI were found to be similar to the positive control, epigallocatechin gallate (EGCG). CTL and TI enhanced the CE formation and filaggrin mRNA expression levels and showed potent activities compared to that in the positive control, 1.5 mM Ca2+. In additionally, CTL and TI showed 5α-reductase inhibitory activities in a dose-dependent manner.ConclusionThe results showed that CTL and TI inhibit AV endogenous factors such as 5α-reductase and inflammatory cytokines and affect exogenous factors such as developing skin barrier function (CE and filaggrin levels). Therefore, CTL and TI may be plant-derived agent, promising in the treatment of acne vulgaris.

Association Between Soluble Lectinlike Oxidized Low-Density Lipoprotein Receptor-1 and Coronary Artery Disease in Psoriasis

Psoriasis, a chronic inflammatory skin disease associated with accelerated noncalcified coronary burden (NCB) by coronary computed tomography angiography (CCTA), accelerates lipoprotein oxidation in the form of oxidized modified lipoproteins. A transmembrane scavenger receptor for these oxidized modified lipoproteins is lectinlike oxidized low-density lipoprotein receptor-1 (LOX-1), which has been reported to be associated with coronary artery disease. It is unknown whether this receptor is associated with coronary artery disease in psoriasis. To assess the association between soluble LOX-1 (sLOX-1) and NCB in psoriasis over time. In a cohort study at the National Institutes of Health, 175 consecutive patients with psoriasis were referred from outpatient dermatology practices between January 1, 2013, and October 1, 2017. A total of 138 consecutively recruited patients with psoriasis were followed up at 1 year. Circulating soluble lectinlike oxidized low-density lipoprotein receptor-1 levels were measured blindly by field scientists running undiluted serum using an enzyme-linked immunosorbent assay. Coronary computed tomography angiography scans were performed to quantify NCB in all 3 major epicardial coronary arteries by a reader blinded to patient demographics, visit, and treatment status. Among the 175 patients with psoriasis, the mean (SD) age was 49.7 (12.6) years and 91 were men (55%). The cohort had relatively low median cardiovascular risk by Framingham risk score (median, 2.0 [interquartile range (IQR), 1.0-6.0]) and had a mean (SD) body mass index (calculated as weight in kilograms divided by height in meters squared) suggestive of overweight profiles (29.6 [6.0]). Elevated sLOX-1 levels were found in patients with psoriasis compared with age- and sex-matched controls (median, 210.3 [IQR, 110.9-336.2] vs 83.7 [IQR, 40.1-151.0]; P < .001), and were associated with Psoriasis Area Severity Index (PASI) score (β = 0.23; 95% CI, 0.082-0.374; P = .003). Moreover, sLOX-1 was associated with NCB independent of hyperlipidemia status (β = 0.11; 95% CI, 0.016-0.200; P = .023), an association which persisted after adjusting for traditional cardiovascular risk factors, statin use, and biologic psoriasis treatment (β = 0.10; 95% CI, 0.014-0.193; P = .03). At 1 year, in those who had clinical improvement in PASI (eg, >50% improvement), a reduction in sLOX-1 (median, 311.1 [IQR, 160.0-648.8] vs median, 224.2 [IQR, 149.1 - 427.4]; P = .01) was associated with a reduction in NCB (β = 0.14; 95% CI, 0.028-0.246; P = .02). Soluble lectinlike oxidized low-density lipoprotein receptor-1 levels were elevated in patients with psoriasis and were associated with severity of skin disease. Moreover, sLOX-1 associated with NCB independent of hyperlipidemia status, suggesting that inflammatory sLOX-1 induction may modulate lipid-rich NCB in psoriasis. Improvement of skin disease was associated with a reduction of sLOX-1 at 1 year, demonstrating the potential role of sLOX-1 in inflammatory atherogenesis in psoriasis.

Durable Responses with Pembrolizumab in Relapsed/Refractory Mycosis Fungoides and Sézary Syndrome: Final Results from a Phase 2 Multicenter Study

Background: Current treatment of advanced stage Mycosis fungoides (MF) and Sézary syndrome (SS) remains unsatisfactory. Complete responses (CR) are typically <10% and partial responses (PR) tend to be short-lived. Antibodies targeting PD1 expressed by healthy tumor-infiltrating T cells can induce long-lasting and deep remissions in cancer patients by activating the host immune response. However, the malignant T-cells of MF/SS also express PD-1. Additionally, genomic alterations involving PD-1, PD-L1, and PD-L2 have been reported in MF/SS, suggesting an important role for the PD-1/PD-L1 axis. We hypothesized that PD-1 checkpoint blockade would be an effective treatment in targeting a T cell malignancy that itself expresses PD-1. Here, we report the efficacy of pembrolizumab in relapsed/refractory MF/SS and correlative biomarker studies.Methods: This single-arm, multicenter study by the Cancer Immunotherapy Trials Network (CITN) enrolled 24 patients with MF/SS stages IB-IV, with at least one prior systemic therapy. Pembrolizumab was administered at 2 mg/kg every 3 weeks for up to two years. The primary endpoint was overall response rate (ORR) using global response criteria according to the ISCL/EORTC consensus guidelines. Skin responses were measured by mSWAT. Secondary endpoints were safety/tolerability, time to response (TTR), duration of response (DOR) and progression-free survival (PFS). Correlative studies included immunohistochemistry (IHC), mass cytometry, whole exome sequencing, gene expression profiling, and serum cytokine analysis.Results: Patients had advanced stage disease (23/24 with stage IIB-IV MF/SS), and were heavily pretreated (median of 4 prior systemic therapies). The ORR was 38% with 2 CR and 7 PR. Of the 9 responding patients, 6 had ≥90% improvement in skin disease by mSWAT. The median TTR was 11 weeks. Responses were durable, with 8 of 9 responses ongoing at last follow up (median DOR 64 weeks, range 32-153 weeks). One responding patient progressed 2 months after discontinuing treatment due to an adverse event (AE). The median PFS was not reached. Overall, the toxicity profile was similar to prior studies of pembrolizumab. Four patients discontinued treatment due to treatment related serious AEs of duodenitis, pneumonitis, hepatitis, and corneal ulcer. Skin flare reactions were observed early in the treatment course in 40% of patients with SS, but none with MF. The skin flare reactions did not result in any treatment discontinuation, and did not correlate with subsequent response to treatment.There was no significant association between response and clinical characteristics including stage, disease type (MF vs. SS), or number of prior therapies. IHC assessment of PD-1, PD-L1, and PD-L2 did not predict response. Treatment resulted in an increase of PD-L1 expression by both IHC and nanoString analysis. A nanoString18 gene signature of tumor inflammation that is predictive of response to pembrolizumab in other tumor types was not predictive in this cohort. High dimensional mass cytometry enabled precise identification and phenotyping of malignant T cells. There was a positive correlation between PD-1 expression on the malignant T cells and development of the skin flare reaction. Whole exome sequencing revealed genomic disruptions of PD-1 signaling including copy loss of PD-1. No associations were found between outcomes and genomic events involving the PD1/PD-L1 axis, total mutation number, or neoantigen numbers.Conclusions: The 38% ORR rate in this heavily pretreated population was 38% with a highly encouraging DOR of 64 weeks. No predictive biomarkers have emerged thus far, but additional studies are ongoing. Additional combination studies with pembrolizumab are warranted to improve response rates. [Display omitted] DisclosuresKhodadoust:Innate Pharma: Research Funding. Porcu:Innate Pharma: Consultancy. Foss:Miragen: Consultancy, Speakers Bureau; Seattle genetics: Consultancy; Spectrum: Consultancy; Mallinkrodt: Consultancy. Moskowitz:Bristol Myers-Squibb: Consultancy, Research Funding; Seattle Genetics: Consultancy, Honoraria, Research Funding; Incyte: Research Funding; Merck: Research Funding; Takeda: Honoraria; ADC Therapeutics: Research Funding. Shustov:Seattle Genetics: Research Funding. Sokol:Seattle Genetics: Consultancy; Mallinckrodt Pharmaceuticals: Consultancy; Spectrum Pharmaceuticals: Consultancy. Yearley:Merck: Employment. Horwitz:Mundipharma: Consultancy; Celgene: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; ADC Therapeutics: Consultancy, Research Funding; Kyowa-Hakka-Kirin: Consultancy, Research Funding; Forty Seven: Consultancy, Research Funding; Millennium/Takeda: Consultancy, Research Funding; Infinity/Verastem: Consultancy, Research Funding; Aileron Therapeutics: Consultancy, Research Funding; Portola: Consultancy; Trillium: Consultancy; Innate Pharma: Consultancy; Spectrum: Research Funding; Corvus: Consultancy. Kim:miRagen: Research Funding; Horizon Pharma: Consultancy, Research Funding; Neumedicine: Consultancy, Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Galderma: Research Funding; Soligenix: Research Funding; Eisai: Membership on an entity's Board of Directors or advisory committees, Research Funding; Tetralogic: Research Funding; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees; Portola: Research Funding; Merck: Research Funding; Medivir: Membership on an entity's Board of Directors or advisory committees; Kyowa-Kirin-Pharma: Membership on an entity's Board of Directors or advisory committees, Research Funding; Innate Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Forty Seven Inc: Research Funding.

Chronic Stress-Related Neural Activity Associates With Subclinical Cardiovascular Disease in Psoriasis: A Prospective Cohort Study

ObjectivesThis study hypothesized that there is an association between chronic stress (as indexed by resting amygdalar activity [AmygA]), hematopoietic system activity (HMPA), and subclinical cardiovascular indexes (aortic vascular inflammation [VI] and noncalcified coronary plaque burden [NCB]) in psoriasis (PSO). The study also hypothesized that treatment of PSO would improve these parameters. BackgroundPSO is a stress-related chronic inflammatory condition that is associated with increased prevalence of subclinical cardiovascular disease (CVD). In individuals without PSO, stress has been linked to CVD through a serial biological pathway that involves the amygdala, hematopoietic tissues, and atherosclerotic plaques. MethodsA total of 164 consecutive patients with PSO and 47 healthy volunteers underwent 18-fluorodeoxyglucose positron emission tomography/computed tomography scans for assessment of AmygA, HMPA, and VI, as well as coronary computed tomography angiography scans for quantifying NCB. Furthermore, a consecutive subset of 30 patients with severe PSO (Psoriasis Area Severity Index Score >10) were followed at 1 year to assess the relationship between skin disease improvement and AmygA, HMPA, VI, and NCB. ResultsThe PSO cohort was middle-aged (mean age: 50 years), had low cardiovascular risk (Framingham risk score: median: 3) and had mild to moderate PSO activity (median Psoriasis Area Severity Index Score: 5.6). AmygA was higher in patients with PSO compared to volunteer participants. AmygA was associated with HMPA (bone marrow activity: β = 0.20, p = 0.01) and subclinical CVD (VI: β = 0.31, p < 0.001; NCB: β = 0.27, p < 0.001) The AmygA−CVD association was in part mediated by HMPA (VI: 20.9%, NCB: 36.7%). Following 1 year of PSO treatment in those with severe disease, improvement in skin disease was accompanied by a reduction in AmygA, bone marrow activity, and VI, with no progression of NCB. ConclusionsIn PSO, a chronic inflammatory disease state, AmygA, which is a manifestation of chronic stress, substantially contributes to the risk of subclinical CVD. Additional studies that use psychometric measures of stress are required to explore therapeutic impact.

164 Long-term (four year) 28-joint count disease activity score (C-reactive protein) remission and improvements in skin disease with apremilast: phase III results from PALACE3

164 Long-term (four year) 28-joint count disease activity score (C-reactive protein) remission and improvements in skin disease with apremilast: phase III results from PALACE3

Pembrolizumab for Treatment of Relapsed/Refractory Mycosis Fungoides and Sezary Syndrome: Clinical Efficacy in a Citn Multicenter Phase 2 Study

Pembrolizumab for Treatment of Relapsed/Refractory Mycosis Fungoides and Sezary Syndrome: Clinical Efficacy in a Citn Multicenter Phase 2 Study

Switching from a biological therapy to another biologic agent in psoriatic patients: the experience of PsOMarche group.

Switching is a "hot" topic and the main reasons for switching prior biologic agent are for a primary failure, a secondary failure or drug intolerance, patient's dissatisfaction, physician decision. The aim of the study was to assess the optimization of the switching from a biologic agent to another. Five Dermatological Units have participated to PsOMarche working group have studied thirty-eight patients affected moderate to severe chronic plaque psoriasis at time 0 (patient recruitment at time of switching from biological therapy to another), 8 weeks (T8), 16 weeks (T16). Twenty-eight males and 10 females were included in the study. At T0, 18 of 22 patients treated with etanercept had been switched to adalimumab and 4 to ustekinumab. Among 10 patients treated with adalimumab, 5 had been switched to ustekinumab, 2 to golimumab and 3 to certolizumab pegol. One patient treated with Infliximab and 5 patients treated with ustekinumab had been switched to adalimumab. Switching had been performed for primary inefficacy in 9 patients (23.6%) and a secondary failure was evidenced in 29 patients (73.4%). PASI75 was achieved in 53% and in 89.4% of patients after 8 weeks and 16 weeks of switching to the second biologic agent respectively; similarly, PsoDISK score significantly decreased at T8 and T16. The experience of PsOMarche group have shown that the switching to a biologic agent to another is a valuable treatment choice in patients with moderate to severe psoriasis experiencing a treatment failure with one biologic therapy, leading to a good improvement in skin disease and in patient's quality of life.

Efficacy of adalimumab across subgroups of patients with moderate‐to‐severe chronic plaque psoriasis of the hands and/or feet: post hoc analysis of REACH

BackgroundThe Randomized Controlled Evaluation of Adalimumab in Treatment of Chronic Plaque Psoriasis of the Hands and Feet (REACH) trial demonstrated that adalimumab was efficacious and well-tolerated for the treatment of hand and/or foot psoriasis through 28 weeks.ObjectiveTo evaluate the effects of patient baseline characteristics on efficacy of adalimumab treatment of hand and/or foot psoriasis.MethodsPatients with moderate-to-severe chronic plaque psoriasis of the hands and/or feet were randomized 2: 1 to adalimumab or placebo during the 16 week, double-blind period of REACH. Primary endpoint was percentage of patients achieving Physician’s Global Assessment of the hands and/or feet of clear/almost clear at week 16. Post hoc analyses evaluated effects of baseline patient characteristics on the primary endpoint. Patients with nail psoriasis at baseline were assessed for association of Nail Psoriasis Severity Index (NAPSI) 50 response with efficacy outcomes at week 16.ResultsSeventy-two patients (49 adalimumab: 23 placebo) were analysed. Greater percentages of adalimumab-treated patients achieved the primary endpoint vs. placebo across all subgroups. Among 31 patients with nail psoriasis, a greater percentage of adalimumab-treated patients achieved NAPSI 50 (56.5%) vs. placebo (12.5%) at week 16. In adalimumab-treated patients, greater percentages of NAPSI 50 Responders vs. Non-responders achieved the primary endpoint, and had greater improvements in erythema, scaling, induration and fissuring, Dermatology Life Quality Index, and pain scores.ConclusionsAdalimumab was efficacious in treating chronic plaque psoriasis of the hands and/or feet over 16 weeks, regardless of baseline characteristics. Marked improvement in nail psoriasis among adalimumab-treated patients correlated with significant improvements in skin disease and patient-reported outcomes.

The Allosteric CXCR1/2 Inhibitor DF2156A Improves Experimental Epidermolysis Bullosa Acquisita

Cytokines are an integral part of host response. However, aberrant cytokine responses are linked to chronic inflammatory diseases, including autoimmune bullous dermatoses (AIBD). AIBD are characterized by autoantibodies against cutaneous structural proteins, mucocutaneous tissue injury, and increased mortality. From the variety of differently expressed cytokines in AIBD, CXCR2 ligands, such as IL-8, seem to be promising therapeutic targets, as these have profound activating effects on neutrophils, which are indispensable for induction of skin lesions in different experimental models of AIBD. Therefore, we analyzed the contribution of CXCR2 ligands in experimental epidermolysis bullosa acquisita (EBA), an AIBD with autoimmunity to type VII collagen (COL7). We first evaluated the impact of the allosteric CXCR1/2 inhibitor DF2156A on neutrophil activation in vitro. The compound significantly reduced IL-8- and combined IL-8/immune complex-induced reactive oxygen species (ROS) release from neutrophils. Next, we noticed an increased expression of CXCL1 and CXCL2 in the skin of mice with experimental EBA. Interestingly, genetic (CXCR2-deficient mice) or pharmacologic inhibition (DF2156A) of CXCR2 function had only moderate and strain-dependent inhibitory effects in an antibody transfer model of EBA. In contrast, in a chronic, immunization-induced EBA mouse model, DF2156A showed profound therapeutic effects, which were comparable to high doses of systemic corticosteroids. Improvement of skin disease by blocking CXCR2 ligand function was independent of changes in circulating and tissue-bound anti-COL7 antibodies, excluding effects on adaptive immune cells. In summary, we here provide evidence that modulation of CXCR1/2 has therapeutic effects in EBA, a prototypical organ-specific autoimmune disease.

Sustained improvement in skin disease–specific quality of life in patients with moderate to severe psoriasis receiving ustekinumab maintenance therapy: Long-term results from PHOENIX 1

Sustained improvement in skin disease–specific quality of life in patients with moderate to severe psoriasis receiving ustekinumab maintenance therapy: Long-term results from PHOENIX 1

Suppression of skin and kidney disease by inhibition of spleen tyrosine kinase in lupus‐prone mice

Spleen tyrosine kinase (Syk) is involved in membrane-mediated signaling in various cells, including immune cells. It is overexpressed in T cells from patients with systemic lupus erythematosus (SLE), and its inhibition has been shown to improve T cell function as well as to improve disease manifestations in (NZB x NZW)F(1) lupus-prone mice and in patients with rheumatoid arthritis. While clinical trials examining Syk inhibition in patients with SLE are being considered, the aim of our experiments was to determine whether the therapeutic effects of Syk inhibition extend to other strains of lupus-prone mice and whether they result in improvement in skin disease and modification of established disease. Female MRL/lpr or BAK/BAX mice were studied. Starting either at age 4 weeks (before disease) or at age 16 weeks (after established disease) and continuing for up to 16 weeks, mice were fed chow containing the Syk inhibitor R788 or control chow. We found that inhibition of Syk in MRL/lpr and BAK/BAX mice prevented the development of skin disease and significantly reduced established skin disease. Similarly, Syk inhibition reduced the size of the spleen and lymph nodes, suppressed the development of renal disease, and suppressed established renal disease. Discontinuation of treatment resulted in extended suppression of skin disease for at least 8 weeks and suppression of renal disease for 4 weeks. Syk inhibition suppresses the development of lupus skin and kidney disease in lupus-prone mice, suppresses established disease in lupus-prone mice, and may represent a valuable treatment for patients with SLE.

Adalimumab for long-term treatment of psoriatic arthritis: 2-year data from the Adalimumab Effectiveness in Psoriatic Arthritis Trial (ADEPT)

Objective:To evaluate the long-term effectiveness and tolerability of adalimumab in the treatment of psoriatic arthritis (PsA).Methods:Patients with PsA who completed a 24-week, double-blind study of adalimumab versus placebo were eligible...

Mycophenolate Mofetil as an Effective Corticosteroid-Sparing Therapy for Recalcitrant Dermatomyositis

Dermatomyositis (DM) is a multisystem idiopathic inflammatory disorder that most commonly affects the muscles and skin. Systemic corticosteroids are the mainstay of therapy but are limited by their long-term adverse effects. We sought to evaluate the effectiveness of oral mycophenolate mofetil in patients with cutaneous lesions of DM recalcitrant to other therapies through an open-label retrospective medical chart review of patients in a university-affiliated private practice setting. Twelve patients with DM who had skin lesions recalcitrant to traditional therapies or who developed toxic effects from traditional therapies began mycophenolate mofetil treatment at doses ranging from 500 mg to 1 g twice a day. Response was based on improvement in skin disease as judged clinically, an increase in strength, and/or an ability to decrease or discontinue concomitant therapies. Improvement was seen in 10 of the 12 patients, most within 4 to 8 weeks. Most patients tolerated mycophenolate mofetil treatment without problem; however, 1 patient developed a B-cell lymphoma of the central nervous system, and another developed abnormal levels of hepatic enzymes along with urinary symptoms. Resolution of these toxic reactions occurred with cessation of mycophenolate mofetil treatment in each patient. Mycophenolate mofetil may be an effective corticosteroid-sparing therapy for the treatment of some patients with DM.

Chemotherapy with etoposide, vincristine, doxorubicin, bolus cyclophosphamide, and oral prednisone in patients with refractory cutaneous T-cell lymphoma

This Phase II study was undertaken to assess the efficacy and toxicity of chemotherapy with etoposide, vincristine, doxorubicin, bolus cyclophosphamide, and oral prednisone (EPOCH regimen) in patients with advanced, refractory cutaneous T-cell lymphoma (CTCL). Fifteen patients were treated with a 96-hour continuous infusion of etoposide, vincristine, doxorubicin, bolus cyclophosphamide, and oral prednisone, followed by granulocyte-colony stimulating factor support and trimethoprim/sulfamethoxazole prophylaxis. The median age of the patients was 53 years (range, 17-82 years). Six patients had Sézary syndrome (SS), four patients had visceral involvement, and four patients had anaplastic large cell morphology, three with Ki-1 (CD30) positivity. All patients had disease that was refractory to prior chemotherapy or electron beam irradiation and eight of these patients had received cyclophosphamide, doxorubicin, vincristine, and prednisone. Seven patients had received prior interferon therapy and nine patients had received fludarabine and/or 2-CDA. After a median of 5 cycles (range, 1-9 cycles), 4 patients achieved a complete response (27%) and 8 patients achieved a partial response (53%) for an overall response rate of 80% (95% confidence interval, 52-96%). Three patients with visceral involvement, two of three patients with anaplastic large cell morphology, and one patient with human T-cell lymphoma virus leukemia/lymphoma did not respond. All 12 responders had improvement in skin disease; 2 of 6 patients with SS had complete disappearance of circulating Sézary cells. The median progression free survival was 8.0 months (range, 3-22 months). After a median follow-up of 11.4 months (range, 2-56+ months), the median patient survival was 13.5 months. Grade 3 or 4 hematologic toxicity occurred in 8 patients (61%); 5 of these 8 patients had febrile neutropenia. Six patients developed staphylococcal bacteremia, two patients had disseminated herpes infection, and one patient had Pneumocystis carinii pneumonia. Grade 3 neurotoxicity occurred in one patient. Two patients had a significant decrease in left ventricular ejection fraction and one patient had supraventricular tachycardia. EPOCH chemotherapy has a high response rate with acceptable toxicity in patients with advanced and refractory CTCL.

Treatment of Acute Graft-Versus-Host Disease With Anti-CD3 Monoclonal Antibodies

A dose-escalation trial was carried out to determine the efficacy and safety of using an IgG2a anti-CD3 monoclonal antibody to treat acute graft-v-host disease (GVHD) in marrow transplant recipients. Two patients received the antibody as the initial treatment of GVHD, and 22 patients received the antibody after failure of initial treatment with corticosteroids, cyclosporine, antithymocyte globulin (ATG), or combined ATG and cyclosporine. Antibody was administered at four dose levels, beginning at approximately 0.015 mg/kg/d and increasing by threefold increments. The initial doses of antibody were nearly always associated with fever and chills, and treatment had to be discontinued in one patient because of intolerable side effects. Improvement in skin disease could be reliably achieved at a dose of 0.15 mg/kg/d, but threefold higher doses appeared to be necessary for improvement in the liver or gut. In no case was there complete resolution of all manifestations of disease, and all patients surviving after antibody treatment required additional immunosuppressive treatment. Four patients developed Epstein-Barr virus (EBV)-associated lymphoproliferative disorders within seven to 18 days after starting antibody therapy. The overall risk of this complication in patients not given anti-CD3 monoclonal antibody is less than 1%. Anti-CD3 antibody represents an effective immunosuppressive agent for treatment of acute GVHD, but this treatment is associated with a substantial risk of EBV-associated lymphoproliferative disorders.