Adalimumab for nail psoriasis: Efficacy and safety from the first 26 weeks of a phase 3, randomized, placebo-controlled trial.

BACKGROUND: Previous clinical trials have not evaluated improvement in nail psoriasis as a primary end point. OBJECTIVE: This phase 3 trial evaluated the safety and efficacy of adalimumab in patients with moderate-to-severe fingernail psoriasis and moderate-to-severe plaque psoriasis. METHODS: Patients were randomized 1:1 to 40 mg adalimumab every other week or placebo. The primary efficacy end point was at least 75% improvement in total-fingernail modified Nail Psoriasis Severity Index (NAPSI75) response rate at week 26. Ranked secondary end point scores evaluated at week 26 were total-fingernail NAPSI and modified NAPSI, nail pain, Nail Psoriasis Physical Functioning Severity, Brigham Scalp Nail Inverse Palmo-Plantar Psoriasis Index, and Physician's Global Assessment (fingernail psoriasis). RESULTS: Of the 217 randomized patients (108 received placebo and 109 received adalimumab), 188 (86.6%) completed 26 weeks of treatment (period A) or escaped early to the open-label period. The study met the primary end point (response rate of 3.4% with placebo vs 46.6% with adalimumab [P < .001]) and all ranked secondary end points. The serious adverse event rates (placebo vs adalimumab) in period A were 4.6% versus 7.3%; the serious infections rates were 1.9% versus 3.7%. LIMITATIONS: Patients with less than 5% BSA involvement were not eligible for enrollment. CONCLUSIONS: After 26 weeks of adalimumab treatment, significant improvements were seen in the primary and all ranked secondary end points and in signs and symptoms of moderate-to-severe nail psoriasis versus with placebo and no new safety risks were identified.

Early Improvements with Guselkumab Associate with Sustained Control of Psoriatic Arthritis: Post hoc Analyses of Two Phase 3 Trials.

INTRODUCTION: Patterns of treatment response can inform clinical decision-making. This study assessed the course and impact of achieving minimal clinically important improvement (MCII) in clinical measures and patient-reported outcomes (PROs) with guselkumab in patients with active psoriatic arthritis (PsA). METHODS: Post hoc analyses evaluated 1120 patients with PsA receiving guselkumab every 4 or 8 weeks (Q4W/Q8W) or placebo from DISCOVER-1 (31% tumor necrosis factor inhibitor-experienced) and DISCOVER-2 (biologic-naïve). Achievement of MCII in clinical Disease Activity Index for PsA (cDAPSA), patient global assessment (PtGA) of arthritis, PtGA of psoriasis, patient-reported pain, Functional Assessment of Chronic Illness Therapy-Fatigue, Health Assessment Questionnaire-Disability Index, 36-item Short-Form Health Survey Physical Component Summary score, PtGA Arthritis + Psoriasis, and PsA Disease Activity Score (PASDAS) was compared between the guselkumab and placebo groups using Cox regression. Logistic regression adjusting for baseline factors evaluated associations between early (W4/W8) MCII achievement and stringent response (≥%50/%70 improvement in American College of Rheumatology response criteria, cDAPSA low disease activity [LDA], PASDAS LDA, and minimal disease activity) at W24/W52 among guselkumab-randomized patients. RESULTS: Among patients with highly active PsA (baseline cDAPSA = 44.1-45.0, PASDAS = 6.4-6.5), times to MCII were significantly faster for guselkumab vs. placebo (hazard ratios 1.3-2.5; P < 0.05). Across measures, at first timepoint assessed, MCII rates were significantly higher with guselkumab (Q4W/Q8W 28-68%/29-65%) vs. placebo (19-47%; both P < 0.05). Early (W4/W8) MCII with guselkumab associated with higher odds of achieving stringent responses at W24/W52 (odds ratios 1.4-17.2/1.4-5.4). CONCLUSIONS: In a mixed PsA population, significant proportions of patients treated with guselkumab achieved early (W4/W8) MCII across clinical and PRO measures, which associated with a higher likelihood of attaining clinically relevant improvements and low levels of disease activity at W24/W52. TRIAL REGISTRATION: DISCOVER-1 (NCT03162796). DISCOVER-2 (NCT03158285).

Depression in psoriatic arthritis: Related to socio-demographics, comorbid loads or disease activity?

AIM: Psychological distress commonly occurs in patients with psoriatic arthritis (PsA). The primary objective of this study was to determine the prevalence of depression in PsA. The secondary objective was to explore its associated factors, including socio-demographics, disease activity data and comorbidities. METHODS: Patients with PsA fulfilling the Classification Criteria for Psoriatic Arthritis were consecutively recruited from local rheumatology clinics. Depression was assessed by a self-administered Chinese-Cantonese version of the Hospital Anxiety and Depression Scale (HADS). RESULTS: Two hundred and eight eligible patients with PsA were recruited, with 82 females and 126 males. Depression was found in 62 (29.8%) of them. The univariate model identified these associated factors: (1) Psoriasis Area and Severity Index score; (2) disease activity measurement, that is tender and swollen joint count, erythrocyte sedimentation rate, C-reactive protein, Disease Activity in Psoriatic Arthritis (DAPSA) score, Leeds Enthesitis Index and tender dactylitis count; (3) quality of life measurement, that is Health Assessment Questionnaire - Disability Index (HAQ-DI), pain and general health perception; (4) PsA duration; and (5) body mass index. The final regression model identified DAPSA and HAQ-DI were closely associated with depression, P = .007 and P = .02 respectively. Moderate and strong correlations with HADS score were found with DAPSA (Kendall's tau-b coefficient [τb] = 0.25) and HAQ-DI (τb = 0.4) respectively. No associations with depression were found between age, living and employment status, gender, demographics, inflammatory markers, disease duration, skin involvement and comorbidities, in term of Charlson's Comorbidity Index. CONCLUSION: Depression was prevalent among PsA patients and it was closely correlated with disease activity and physical function impairment. Achieving low disease activity and maintaining physical function in patients with PsA may mitigate the psychological burden. The present study also highlighted the unmet needs of strategies to identify this common phenomenon.

Modulation of psoriatic-like skin inflammation by traditional Indian medicine Divya-Kayakalp-Vati and Oil through attenuation of pro-inflammatory cytokines.

Background and aim: Psoriasis (Ps) is a chronic skin inflammatory disorder, that progresses to scaly-red dermal plaque formations associated with inflammation. Divya-Kayakalp-Vati (DKV) and Divya-Kayakalp-Oil (DKO) are traditional Ayurveda herbo-mineral formulations, that are prescribed for the treatment of inflammatory dermal ailments. In the present study, we evaluated the efficacy of Divya-Kayakalp-Vati and Divya-Kayakalp-Oil (DKV-O) combined treatment in ameliorating Ps-like skin inflammation under in-vitro and in-vivo conditions. Experimental procedure: Efficacy of DKV-O was analyzed in λ-carrageenan-treated Wistar rats paw edema and 12-O-tetradecanoylphorbol 13-acetate (TPA)-treated CD-1 mouse ear edema models through physiological and histopathological analysis. Mode of action for the DKV-O was studied in LPS-stimulated THP-1 cells through pro-inflammatory cytokine analysis. Observed effects were correlated to the phytochemicals constituents of DKV-O analyzed using the HPLC method. Result and conclusion: DKV and DKO formulations were individually found to contain phytochemicals Gallic acid, Catechin, Berberine, Curcumin, Phenol and Benzoic acid. DKV-O treatment significantly reduced the paw volume and edema in Wistar rats stimulated through λ-carrageenan-treatment. Furthermore, DKV-O treatment significantly reduced the ear edema and enhanced biopsy weight, epidermal thickness, inflammatory lesions and influx of neutrophils stimulated by TPA-treatment in CD-1 mice. DKV alone ameliorated the LPS-stimulated release of Interleukin (IL)-6, IL-17A, IL-23, and Tumor Necrosis Factor-alpha cytokines in the THP-1 cells.Taken together, DKV-O showed good efficacy in ameliorating acute systemic inflammation stimulated by effectors such as, λ-carrageenan and TPA in animal models. Hence, Divya-Kayakalp-Vati and Divya-Kayakalp-Oil co-treatment can be further explored as an anti-inflammatory treatment against dermal diseases like psoriasis and atopic dermatitis.

Fatigue in psoriatic arthritis: Is it related to disease activity?

AIM: Fatigue is commonly associated with psoriatic arthritis (PsA). However, information about its prevalence and associated factors is sparse. The primary objective here was to find the prevalence and magnitude of PsA fatigue. The secondary objective was to explore its associated risk factors, particularly emphasis on the effect of disease activity control. METHODS: PsA patients who fulfilled Classification Criteria For Psoriatic Arthritis were consecutively recruited from local rheumatology clinics. Fatigue was assessed by a 13-item self-administered questionnaire (Functional Assessment of Chronic Illness Therapy - Fatigue [FACIT-F]) (0-52). Data collected and analyzed included: demographic data, disease activity data, comorbidities and medications use. RESULTS: There were 231 eligible PsA patients recruited. The mean FACIT-F score was 37.5 ± 9.1. Severe fatigue, defined as FACIT-F score < 30, was found in 49 (22.1%) of them. The univariate model identified these associated factors of fatigue: tender and swollen joint count, dactylitis count, Psoriasis Area and Severity Index (PASI) score, pain and general health perception, Disease Activity in Psoriatic Arthritis (DAPSA) score, Health Assessment Questionnaire, the use of cyclosporine, sulphasalazine and biologic agents. The final regression model identified DAPSA and PASI were closely associated with severe fatigue (P = .003 and P = .04 respectively). No associations with fatigue were found between age, gender, disease duration, comorbidities and medication use. However, there were weak correlations between the magnitude of FACIT-F score, DAPSA and PASI with r = -.3 and r = -.26 respectively. CONCLUSION: Severe fatigue was common in PsA patients, and its magnitude was closely correlated with DAPSA and PASI score, indicating its multifactorial nature. Achieving DAPSA and PASI remission could significantly alleviate the fatigue intensity to a certain extent. However, treatment for PsA-related fatigue should adopt a multidisciplinary approach in addition to disease activity control.

The Brain-Skin Connection and the Pathogenesis of Psoriasis: A Review with a Focus on the Serotonergic System.

Psoriasis is a common non-communicable chronic immune-mediated skin disease, affecting approximately 125 million people in the world. Its pathogenesis results from a combination of genetic and environmental factors. The pathogenesis of psoriasis seems to be driven by the interaction between innate immune cells, adaptive immune cells and keratinocytes, in a process mediated by cytokines (including interleukins (IL)-6, IL-17 and IL-22, interferon and tumor necrosis factor) and other signaling molecules. This leads to an inflammatory process with increased proliferation of epidermal cells, neo-angiogenesis and infiltration of dendritic cells in the skin. Dysfunctional de novo glucocorticoid synthesis in psoriatic keratinocytes and the skin microbiome have also been suggested as mediators in the pathogenesis of this disease. To understand psoriasis, it is essential to comprehend the processes underlying the skin immunity and neuroendocrinology. This review paper focuses on the skin as a neuroendocrine organ and summarizes what is known about the skin immune system, the brain-skin connection and the role played by the serotonergic system in skin. Subsequently, the alterations of neuroimmune processes and of the serotonergic system in psoriatic skin are discussed, as well as, briefly, the genetic basis of psoriasis.

Human Embryonic Stem Cells-Derived Mesenchymal Stem Cells Reduce the Symptom of Psoriasis in Imiquimod-Induced Skin Model.

BACKGROUND: Mesenchymal stem cells (MSCs) can be used for a wide range of therapeutic applications because of not only their differentiation potential but also their ability to secrete bioactive factors. Recently, several studies have suggested the use of human embryonic stem cell-derived MSCs (hE-MSCs) as an alternative for regenerative cellular therapy due to mass production of MSCs from a single donor. METHODS: We generated hE-MSCs from embryonic stem cell lines, SNUhES3, and analyzed immune properties of these cells. Also, we evaluated the in-vivo therapeutic potential of hE-MSCs in immune-mediated inflammatory skin disease. RESULTS: The cell showed the suppression of immunity associated with allogenic peripheral blood mononuclear cells in mixed lymphocyte response assay. We also detected that cytokines and growth factor related to the immune response were secreted from these cells. To assessed the in-vivo therapeutic potential of hE-MSCs in immune-mediated inflammatory skin disease, we used imiquimod (IMQ)-induced skin psoriasis mouse model. The score of clinical skin was significantly reduced in the hE-MSCs treated group compared with control IMQ group. In histological analysis, the IMQ-induced epidermal thickness was significantly decreased by hE-MSCs treatment. It was correlated with splenomegaly induced by IMQ which was also improved in the hE-MSCs. Moreover, IMQ-induced inflammatory cytokines; Th1 cytokines (TNF-α, IFN-α, IFN-γ,and IL-27) and Th17 cytokines (IL-17A and IL-23), in the serum and skin showed marked inhibition by hE-MSCs. CONCLUSION: These results suggested that hE-MSCs have a potency of immune modulation in psoriasis, which might be the key factor for the improved psoriasis.

Hyperuricemia in Asian psoriatic arthritis patients.

AIM: It is generally accepted that hyperuricemia is commonly associated with psoriatic arthritis (PsA). However, variations in ethnicity, diet and habitat may contribute to differences in prevalence and risk factors for hyperuricemia in PsA patients. Moreover, Asian specific data is deficient. The primary objective of the present study was to determine the prevalence of hyperuricemia among PsA patients. The secondary objective was to explore its associated risk factors. METHODS: This was a multi-center, cross-sectional observational study of 160 PsA patients from local Rheumatology clinics. Serum uric acid (SUA) level and other clinical parameters were measured and hyperuricemia was defined as SUA level greater or equal to 360 umol/L in females and 420 umol/L in males. RESULTS: Forty-nine of 160 patients (30.6%) had hyperuricemia, of which 32 were men, 17 were women. Among those with hyperuricemia, mean SUA level was 500.7 ± 95.9 umol/L and 427.8 ± 83.1 umol/L in males and females, respectively. Univariate analysis found: (i) overweight status; (ii) obesity; (iii) Psoriasis Area and Severity Index; (iv) body surface area; (v) severe skin involvement, as being potentially associated with hyperuricemia. Regression model identified overweight status increased the likelihood of hyperuricemia in PsA, with an odds ratio of 4.4 (95% CI: 2.0-9.5). Furthermore, there was moderately positive correlation (r = 0.37) between body mass index (BMI) and SUA level. No associations were found between arthritis conditions and duration, lipid profile, creatinine clearance; and hyperuricemia. CONCLUSION: A significant proportion of PsA patients had asymptomatic hyperuricemia. It was closely related with BMI, which represented metabolic dysregulation; but not with severity of skin disease, joint involvement or renal function.