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1.
Trends Biotechnol ; 2024 Mar 27.
Article in English | MEDLINE | ID: mdl-38538499

ABSTRACT

Can drug and vaccine regulatory agencies leverage their experience during the coronavirus disease 2019 (COVID-19) pandemic to advance from reactive regulation to adaptive regulation and beyond to anticipatory regulation to prevent or curb future pandemics?

2.
J Am Acad Dermatol ; 90(6): 1170-1181, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38331098

ABSTRACT

BACKGROUND: For psoriatic patients who need to receive nonlive or live vaccines, evidence-based recommendations are needed regarding whether to pause or continue systemic therapies for psoriasis and/or psoriatic arthritis. OBJECTIVE: To evaluate literature regarding vaccine efficacy and safety and to generate consensus-based recommendations for adults receiving systemic therapies for psoriasis and/or psoriatic arthritis receiving nonlive or live vaccines. METHODS: Using a modified Delphi process, 22 consensus statements were developed by the National Psoriasis Foundation Medical Board and COVID-19 Task Force, and infectious disease experts. RESULTS: Key recommendations include continuing most oral and biologic therapies without modification for patients receiving nonlive vaccines; consider interruption of methotrexate for nonlive vaccines. For patients receiving live vaccines, discontinue most oral and biologic medications before and after administration of live vaccine. Specific recommendations include discontinuing most biologic therapies, except for abatacept, for 2-3 half-lives before live vaccine administration and deferring next dose 2-4 weeks after live vaccination. LIMITATIONS: Studies regarding infection rates after vaccination are lacking. CONCLUSION: Interruption of antipsoriatic oral and biologic therapies is generally not necessary for patients receiving nonlive vaccines. Temporary interruption of oral and biologic therapies before and after administration of live vaccines is recommended in most cases.


Subject(s)
Arthritis, Psoriatic , Biological Products , Consensus , Delphi Technique , Psoriasis , Humans , Psoriasis/drug therapy , Arthritis, Psoriatic/drug therapy , Biological Products/therapeutic use , Biological Products/administration & dosage , Administration, Oral , Vaccination/standards , Adult , COVID-19/prevention & control , COVID-19 Vaccines/administration & dosage , SARS-CoV-2 , Methotrexate/therapeutic use , Methotrexate/administration & dosage , Dermatologic Agents/administration & dosage , Dermatologic Agents/therapeutic use
3.
JAAD Int ; 12: 32-36, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37274387

ABSTRACT

Telemedicine emerged as an alternative care delivery system used to offer effective long-term management to patients with chronic, inflammatory conditions such as psoriatic disease. Teledermatology can provide reliable clinical information through thorough history-taking and virtual evaluations that include patient-provided images and disease activity assessment tools that may help accurately diagnose and manage patients with psoriasis. The integration of validated screening tools for psoriatic arthritis and effective teledermatology practices may improve access to specialists, thus avoiding preventable delays in the diagnosis and treatment of patients with psoriatic arthritis. Although the provision of telehealthcare should not completely replace high quality, in-person dermatologic or rheumatologic visits, the convenience and collaborative nature of teledermatology may lead to expanded access and expedited care in the appropriate setting, whether it be in a virtual or in-person visit.

4.
J Rheumatol ; 50(2): 258-264, 2023 02.
Article in English | MEDLINE | ID: mdl-36319005

ABSTRACT

OBJECTIVE: Enthesitis is a key pathological and clinical feature of psoriatic arthritis (PsA) in children and adults. Enthesitis is typically assessed clinically using several validated enthesitis scoring systems that have been used in clinical trials. Enthesitis treatment response has been reported as change in the total enthesitis score or the proportion of patients who achieved complete resolution. The majority of trials in PsA did not require patients to have enthesitis at study entry since enthesitis was evaluated only as a secondary outcome. Despite the inherent limitations of the clinical assessment of enthesitis, imaging of the entheses using ultrasound or magnetic resonance imaging has rarely been used in clinical trials to assess response to treatment of enthesitis. This systematic review summarizes existing evidence regarding pharmaceutical and nonpharmaceutical interventions for enthesitis in patients with PsA to facilitate an evidence-based update of the Group for Research and Assessment in Psoriasis and Psoriatic Arthritis (GRAPPA) treatment recommendations for PsA. METHODS: We performed a systematic literature review to identify 41 randomized clinical trials that reported enthesitis treatment response in patients with PsA. For each intervention, the response effect size was summarized and the quality of evidence was graded. Recommendations were then formulated for the various pharmacological and nonpharmacological therapies. RESULTS: We included 41 randomized clinical trials in our review and graded each intervention. CONCLUSION: Several classes of systemic conventional and advanced therapies and local measures were recommended for active enthesitis in patients with PsA.


Subject(s)
Arthritis, Psoriatic , Enthesopathy , Psoriasis , Adult , Child , Humans , Arthritis, Psoriatic/diagnostic imaging , Arthritis, Psoriatic/drug therapy , Enthesopathy/diagnostic imaging , Enthesopathy/drug therapy , Ultrasonography , Magnetic Resonance Imaging
5.
Front Immunol ; 13: 909760, 2022.
Article in English | MEDLINE | ID: mdl-35720288

ABSTRACT

Background and Objectives: Psoriasis is a heterogeneous inflammatory disease that involves the skin, joints, liver, heart, and other organs. Psoriatic arthritis (PsA) is associated with cardiovascular disease (CVD), but the relative contributions of inflammatory and metabolic dysregulation to CVD are incompletely understood. We set out to discover novel potential contributors to CVD in PsA patients by comprehensively phenotyping a cohort of PsA patients using these advanced technologies. Methods: In this cross-sectional analysis of a cohort study, we investigated associations of systemic inflammation and metabolic dysregulation with Coronary CT angiography (CCTA)-proven coronary artery disease (CAD) in 39 subjects with PsA. We measured traditional CVD risk factors [blood pressure, Body Mass Index (BMI), diabetes, age, sex, smoking], serum markers of systemic inflammation (hsCRP, GlycA) and metabolic dysfunction (cholesterol efflux capacity), and inflammatory cytokines (IL-1ß, IL-6, IL-12/IL-23, IL-17A, TNF-α, IFN-γ). We also incorporated radiographic measures of metabolic dysfunction (visceral and subcutaneous adipose volume) and tissue-specific inflammation (positron emission tomography-computed tomography, PET-CT). To quantify relative contributions of FDG (fluorodeoxyglucose) uptake and adiposity to coronary plaque, we performed multiple linear regression, controlling for Framingham risk score (FRS) and FRS + visceral adiposity. Results: Compared with non-psoriatic volunteers, subjects with PsA had elevated markers of metabolic and inflammatory disease, which was more pronounced in subjects with moderate-to-severe skin disease. This included visceral (p = 0.005) and subcutaneous (p = 0.004) adiposity, BMI (p = 0.001), hemoglobin A1C (p = 0.037), high sensitivity C-reactive protein (p = 0.005), IL-6 (p = 0.003), IFN-γ (p = 0.006), and liver FDG uptake (p = 0.03). In subjects with PsA, visceral adiposity correlated significantly with subclinical CAD (standardized ß = 0.681, p = 0.002), as did FDG uptake in bone marrow (standardized ß = 0.488, p = 0.008), liver (standardized ß = 0.619, p < 0.001), spleen (standardized ß = 0.523, p = 0.004), and subcutaneous adipose (standardized ß = 0.524, p = 0.003). Interpretation: Together, these findings reveal inflammatory and metabolic potential contributors to subclinical CAD in PsA, including adipose inflammation, and suggesting novel targets for CVD prevention and treatment in PsA.


Subject(s)
Arthritis, Psoriatic , Cardiovascular Diseases , Coronary Artery Disease , Arthritis, Psoriatic/complications , Arthritis, Psoriatic/diagnostic imaging , Biomarkers , Cohort Studies , Coronary Artery Disease/diagnostic imaging , Cross-Sectional Studies , Fluorodeoxyglucose F18 , Humans , Inflammation , Interleukin-6 , Positron Emission Tomography Computed Tomography
6.
J Am Acad Dermatol ; 84(5): 1329-1338, 2021 May.
Article in English | MEDLINE | ID: mdl-33383084

ABSTRACT

BACKGROUND: Psoriasis is associated with a heightened risk of cardiovascular disease and higher prevalence of metabolic syndrome. OBJECTIVE: Investigate the effect of metabolic syndrome and its factors on early coronary artery disease assessed as noncalcified coronary burden by coronary computed tomography angiography in psoriasis. METHODS: This cross-sectional study consisted of 260 participants with psoriasis and coronary computed tomography angiography characterization. Metabolic syndrome was defined according to the harmonized International Diabetes Federation criteria. RESULTS: Of the 260 participants, 80 had metabolic syndrome (31%). The metabolic syndrome group had a higher burden of cardiometabolic disease, systemic inflammation, noncalcified coronary burden, and high-risk coronary plaque. After adjusting for Framingham risk score, lipid-lowering therapy, and biologic use, metabolic syndrome (ß = .31; P < .001) and its individual factors of waist circumference (ß = .33; P < .001), triglyceride levels (ß = .17; P = .005), blood pressure (ß = .18; P = .005), and fasting glucose (ß = .17; P = .009) were significantly associated with noncalcified coronary burden. After adjusting for all other metabolic syndrome factors, blood pressure and waist circumference remained significantly associated with noncalcified coronary burden. LIMITATIONS: Observational nature with limited ability to control for confounders. CONCLUSIONS: In psoriasis, individuals with metabolic syndrome had more cardiovascular disease risk factors, systemic inflammation, and noncalcified coronary burden. Efforts to increase metabolic syndrome awareness in psoriasis should be undertaken to reduce the heightened cardiovascular disease risk.


Subject(s)
Coronary Artery Disease/epidemiology , Metabolic Syndrome/epidemiology , Psoriasis/complications , Adult , Blood Pressure , Cardiometabolic Risk Factors , Computed Tomography Angiography , Coronary Angiography , Coronary Artery Disease/diagnosis , Coronary Artery Disease/etiology , Coronary Artery Disease/metabolism , Cross-Sectional Studies , Female , Humans , Longitudinal Studies , Male , Metabolic Syndrome/blood , Metabolic Syndrome/diagnosis , Metabolic Syndrome/metabolism , Middle Aged , Prospective Studies , Psoriasis/blood , Psoriasis/metabolism , Risk Assessment/statistics & numerical data , Tomography, X-Ray Computed , Triglycerides/blood , Waist Circumference
7.
JCI Insight ; 5(22)2020 11 19.
Article in English | MEDLINE | ID: mdl-33104056

ABSTRACT

BACKGROUNDPsoriasis is a chronic inflammatory skin disease associated with increased obesity, noncalcified coronary artery burden (NCB), and incident myocardial infarction. Here, we sought to assess the relationship among inflammation, visceral adipose tissue (VAT), and NCB. Furthermore, we evaluated whether improvement in VAT would be associated with reduction in NCB over time in psoriasis.METHODSConsecutive psoriasis patients underwent coronary CT angiography to quantify NCB and abdominal CT to calculate VAT at baseline (n = 237), 1 year (n = 176), and 4 years (n = 50).RESULTSPatients with high levels of high-sensitivity C-reactive protein (hs-CRP) had significantly greater visceral adiposity (17,952.9 ± 849.2 cc3 vs. 13370.7 ± 806.8 cc3, P < 0.001) and noncalcified coronary burden (1.26 ± 0.03 vs. 1.07 ± 0.02 mm2) than those with low levels of hs-CRP. Those with higher levels of VAT had more systemic inflammation (hs-CRP, median [IQR], 2.5 mg/L [1.0-5.3 mg/L] vs. 1.2 mg/L [0.6-2.9 mg/L]), with approximately 50% higher NCB (1.42 ± 0.6 mm2 vs. 0.91 ± 0.2 mm2, P < 0.001). VAT associated with NCB in fully adjusted models (ß = 0.47, P < 0.001). At 1-year follow-up, patients who had worsening hs-CRP had an increase in VAT (14,748.7 ± 878.1 cc3 to 15,158.7 ± 881.5 cc3; P = 0.03), whereas those who had improved hs-CRP improved their VAT (16,876.1 ± 915.2 cc3 to 16310.4 ± 889.6 cc3; P = 0.04). At 1 year, there was 10.3% reduction in NCB in those who had decreased VAT (ß = 0.26, P < 0.0001), which persisted in a subset of patients at 4 years (ß = 0.39, P = 0.003).CONCLUSIONSInflammation drives development of VAT, increased cardiometabolic risk, and NCB in psoriasis. Reduction of inflammation associated with reduction in VAT and associated with longitudinal improvement in NCB. These findings demonstrate the important role of inflammation in the development of VAT in humans and its effect on early atherogenesis.TRIAL REGISTRATIONClinicalTrials.gov NCT01778569.FUNDINGThis study was supported by the National Heart, Lung, and Blood Institute Intramural Research Program (HL006193-05), the NIH Medical Research Scholars Program, a public-private partnership supported jointly by the NIH and contributions to the Foundation for the NIH from the Doris Duke Charitable Foundation (no. 2014194), the American Association for Dental Research, the Colgate-Palmolive Company, Genentech, and Elsevier as well as private donors.


Subject(s)
Biomarkers/metabolism , Coronary Artery Disease/pathology , Inflammation/complications , Intra-Abdominal Fat/pathology , Psoriasis/physiopathology , Coronary Artery Disease/etiology , Coronary Artery Disease/metabolism , Female , Humans , Male , Middle Aged , Prospective Studies , Risk Factors
8.
Am J Clin Dermatol ; 20(6): 873-880, 2019 Dec.
Article in English | MEDLINE | ID: mdl-31612380

ABSTRACT

BACKGROUND: Information on the factors that influence treatment management decisions for psoriatic arthritis (PsA) is limited. OBJECTIVE: Our objective was to evaluate the impact of clinical specialty setting and geographic region on the management of patients with PsA in the USA. METHODS: LOOP was a multicenter, cross-sectional, observational study conducted across 44 sites in the USA. Patients were aged ≥ 18 years with a suspected or established diagnosis of PsA and were routinely visiting a rheumatologist or dermatologist. All patients enrolled in the study were assessed by both a rheumatologist and a dermatologist. Primary outcomes were the times from symptom onset to PsA diagnosis; PsA diagnosis to first conventional synthetic disease-modifying antirheumatic drug (csDMARD); PsA diagnosis to first biologic DMARD (bDMARD); and first csDMARD to first bDMARD. RESULTS: Of 681 patients enrolled in the study, 513 had a confirmed diagnosis of PsA and were included in this analysis. More patients were recruited by rheumatologists (71.3%) than by dermatologists (28.7%). The median time from symptom onset to diagnosis of PsA was significantly shorter for patients enrolled by rheumatologists than for those enrolled by dermatologists (1.0 vs. 2.6 years; p < 0.001). Disease activity and burden were generally similar across enrolling specialties. However, patients in western areas of the USA had less severe disease than those in central or eastern areas, including measures of joint involvement, enthesitis, and dactylitis. CONCLUSIONS: There was a substantial delay in the time from symptom onset to diagnosis in this study population, and this was significantly longer for patients enrolled in the dermatology versus the rheumatology setting. This supports the need for collaboration across specialties to ensure faster recognition and treatment of PsA.


Subject(s)
Arthritis, Psoriatic/drug therapy , Biological Products/therapeutic use , Practice Patterns, Physicians'/statistics & numerical data , Time-to-Treatment/statistics & numerical data , Adult , Aged , Antirheumatic Agents , Arthritis, Psoriatic/diagnosis , Cross-Sectional Studies , Dermatologists/statistics & numerical data , Female , Geography , Humans , Intersectoral Collaboration , Male , Middle Aged , Rheumatologists/statistics & numerical data , Severity of Illness Index , Time Factors , United States
9.
Arthritis Rheumatol ; 71(1): 5-32, 2019 01.
Article in English | MEDLINE | ID: mdl-30499246

ABSTRACT

OBJECTIVE: To develop an evidence-based guideline for the pharmacologic and nonpharmacologic treatment of psoriatic arthritis (PsA), as a collaboration between the American College of Rheumatology (ACR) and the National Psoriasis Foundation (NPF). METHODS: We identified critical outcomes in PsA and clinically relevant PICO (population/intervention/comparator/outcomes) questions. A Literature Review Team performed a systematic literature review to summarize evidence supporting the benefits and harms of available pharmacologic and nonpharmacologic therapies for PsA. GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology was used to rate the quality of the evidence. A voting panel, including rheumatologists, dermatologists, other health professionals, and patients, achieved consensus on the direction and the strength of the recommendations. RESULTS: The guideline covers the management of active PsA in patients who are treatment-naive and those who continue to have active PsA despite treatment, and addresses the use of oral small molecules, tumor necrosis factor inhibitors, interleukin-12/23 inhibitors (IL-12/23i), IL-17 inhibitors, CTLA4-Ig (abatacept), and a JAK inhibitor (tofacitinib). We also developed recommendations for psoriatic spondylitis, predominant enthesitis, and treatment in the presence of concomitant inflammatory bowel disease, diabetes, or serious infections. We formulated recommendations for a treat-to-target strategy, vaccinations, and nonpharmacologic therapies. Six percent of the recommendations were strong and 94% conditional, indicating the importance of active discussion between the health care provider and the patient to choose the optimal treatment. CONCLUSION: The 2018 ACR/NPF PsA guideline serves as a tool for health care providers and patients in the selection of appropriate therapy in common clinical scenarios. Best treatment decisions consider each individual patient situation. The guideline is not meant to be proscriptive and should not be used to limit treatment options for patients with PsA.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Antirheumatic Agents/therapeutic use , Arthritis, Psoriatic/therapy , Glucocorticoids/therapeutic use , Immunosuppressive Agents/therapeutic use , Physical Therapy Modalities , Abatacept/therapeutic use , Adalimumab/therapeutic use , Antibodies, Monoclonal/therapeutic use , Antibodies, Monoclonal, Humanized/therapeutic use , Arthritis, Psoriatic/epidemiology , Comorbidity , Diabetes Mellitus/epidemiology , Diabetes Mellitus/therapy , Enthesopathy/therapy , Etanercept/therapeutic use , Evidence-Based Medicine , Exercise , Humans , Inflammatory Bowel Diseases/epidemiology , Inflammatory Bowel Diseases/therapy , Infliximab/therapeutic use , Interleukin-12/antagonists & inhibitors , Interleukin-17/antagonists & inhibitors , Interleukin-23/antagonists & inhibitors , Occupational Therapy , Piperidines/therapeutic use , Pyrimidines/therapeutic use , Pyrroles/therapeutic use , Rheumatology , Smoking Cessation , Societies, Medical , Spondylitis/therapy , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Ustekinumab/therapeutic use , Weight Loss
10.
Arthritis Care Res (Hoboken) ; 71(1): 2-29, 2019 01.
Article in English | MEDLINE | ID: mdl-30499259

ABSTRACT

OBJECTIVE: To develop an evidence-based guideline for the pharmacologic and nonpharmacologic treatment of psoriatic arthritis (PsA), as a collaboration between the American College of Rheumatology (ACR) and the National Psoriasis Foundation (NPF). METHODS: We identified critical outcomes in PsA and clinically relevant PICO (population/intervention/comparator/outcomes) questions. A Literature Review Team performed a systematic literature review to summarize evidence supporting the benefits and harms of available pharmacologic and nonpharmacologic therapies for PsA. GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology was used to rate the quality of the evidence. A voting panel, including rheumatologists, dermatologists, other health professionals, and patients, achieved consensus on the direction and the strength of the recommendations. RESULTS: The guideline covers the management of active PsA in patients who are treatment-naive and those who continue to have active PsA despite treatment, and addresses the use of oral small molecules, tumor necrosis factor inhibitors, interleukin-12/23 inhibitors (IL-12/23i), IL-17 inhibitors, CTLA4-Ig (abatacept), and a JAK inhibitor (tofacitinib). We also developed recommendations for psoriatic spondylitis, predominant enthesitis, and treatment in the presence of concomitant inflammatory bowel disease, diabetes, or serious infections. We formulated recommendations for a treat-to-target strategy, vaccinations, and nonpharmacologic therapies. Six percent of the recommendations were strong and 94% conditional, indicating the importance of active discussion between the health care provider and the patient to choose the optimal treatment. CONCLUSION: The 2018 ACR/NPF PsA guideline serves as a tool for health care providers and patients in the selection of appropriate therapy in common clinical scenarios. Best treatment decisions consider each individual patient situation. The guideline is not meant to be proscriptive and should not be used to limit treatment options for patients with PsA.


Subject(s)
Arthritis, Psoriatic/therapy , Clinical Decision-Making , Practice Guidelines as Topic/standards , Rheumatology/standards , Antirheumatic Agents/administration & dosage , Arthritis, Psoriatic/diagnosis , Arthritis, Psoriatic/epidemiology , Biological Products/administration & dosage , Clinical Decision-Making/methods , Drug Therapy, Combination , Humans , Immunosuppressive Agents/administration & dosage , Rheumatology/methods , Treatment Outcome , United States/epidemiology
11.
JAMA Dermatol ; 154(8): 934-950, 2018 08 01.
Article in English | MEDLINE | ID: mdl-29926091

ABSTRACT

Importance: Psoriasis is a chronic, inflammatory skin disease and has significant associated morbidity and effect on quality of life. It is important to determine whether dietary interventions help reduce disease severity in patients with psoriatic diseases. Objective: To make evidence-based dietary recommendations for adults with psoriasis and/or psoriatic arthritis from the Medical Board of the National Psoriasis Foundation. Evidence Review: We used literature from prior systematic reviews as well as additional primary literature from the MEDLINE database from January 1, 2014, to August 31, 2017, that evaluated the impact of diet on psoriasis. We included observational and interventional studies of patients with psoriasis or psoriatic arthritis. The quality of included studies was assessed using the Newcastle-Ottawa scale for observational studies and the Cochrane Risk of Bias Tool for interventional studies. We made evidence-based dietary recommendations, which were voted on by the National Psoriasis Foundation Medical Board. Findings: We identified 55 studies meeting the inclusion criteria for this review. These studies represent 77 557 unique participants of which 4534 have psoriasis. Based on the literature, we strongly recommend dietary weight reduction with a hypocaloric diet in overweight and obese patients with psoriasis. We weakly recommend a gluten-free diet only in patients who test positive for serologic markers of gluten sensitivity. Based on low-quality data, select foods, nutrients, and dietary patterns may affect psoriasis. For patients with psoriatic arthritis, we weakly recommend vitamin D supplementation and dietary weight reduction with a hypocaloric diet in overweight and obese patients. Dietary interventions should always be used in conjunction with standard medical therapies for psoriasis and psoriatic arthritis. Conclusions and Relevance: Adults with psoriasis and/or psoriatic arthritis can supplement their standard medical therapies with dietary interventions to reduce disease severity. These dietary recommendations from the National Psoriasis Foundation Medical Board will help guide clinicians regarding the utility of dietary interventions in adults with psoriatic diseases.


Subject(s)
Arthritis, Psoriatic/diet therapy , Diet , Psoriasis/diet therapy , Adult , Arthritis, Psoriatic/pathology , Diet, Reducing , Humans , Obesity/complications , Obesity/diet therapy , Overweight/complications , Overweight/diet therapy , Psoriasis/pathology , Quality of Life , Recommended Dietary Allowances , Severity of Illness Index , Weight Loss
12.
Health Aff (Millwood) ; 37(5): 724-731, 2018 05.
Article in English | MEDLINE | ID: mdl-29733717

ABSTRACT

Precision medicines can benefit patients by increasing the probability of a successful treatment response in selected patient populations. The potential for more immediate signals of efficacy during clinical trials suggests such medicines will reach the market more rapidly than traditional drugs will. Using data from the Food and Drug Administration (FDA), we examined the regulatory review and pivotal trial characteristics of precision medicines. We found that in the period January 2013-June 2017, precision medicines were developed and reviewed almost two years faster than nonprecision medicines. In addition, approximately 48 percent of the precision medicines in our study qualified for the FDA's breakthrough therapy designation. Precision medicines were also approved based on fewer pivotal trials with fewer patients, and the trials were less likely to be randomized, blinded, or controlled with either an active or placebo comparator.


Subject(s)
Biological Products/administration & dosage , Drug Approval , Precision Medicine/statistics & numerical data , United States Food and Drug Administration , Clinical Trials as Topic , Cross-Sectional Studies , Databases, Factual , Female , Humans , Male , Molecular Targeted Therapy , Pharmaceutical Preparations , Precision Medicine/methods , Statistics, Nonparametric , United States
13.
Arthritis Rheumatol ; 70(3): 408-416, 2018 03.
Article in English | MEDLINE | ID: mdl-29088580

ABSTRACT

OBJECTIVE: To assess the effect of tumor necrosis factor inhibitors (TNFi) on subclinical cardiovascular disease in patients with psoriatic disease. METHODS: We performed a 2-stage study. In stage 1, carotid total plaque area was assessed in patients with psoriasis or psoriatic arthritis (PsA) (n = 319) by ultrasound at baseline and after 2-3 years. The annual progression rate of atherosclerosis was the outcome of interest. In stage 2, PsA patients receiving TNFi (n = 21) and age- and sex-matched PsA patients not receiving any biologic agent (n = 13) underwent 18 F-fluorodeoxyglucose-positron emission tomography/computed tomography at baseline and 1 year to assess vascular inflammation, measured as target-to-background ratio (TBR). In both stages, multivariable regression analyses adjusted for cardiovascular risk factors and use of statins were performed. RESULTS: In stage 1, men had significantly higher atherosclerosis progression than women (P < 0.001). TNFi was associated with reduced atherosclerosis progression in men after controlling for cardiovascular risk and use of statins (adjusted ß = -2.20 [95% confidence interval -3.41, -1.00], P < 0.001). There was no association between TNFi and atherosclerosis progression in women (P = 0.74). In stage 2, patients receiving TNFi had reduced TBR at 1 year (P = 0.03). Those not receiving TNFi had no significant change in TBR (P = 0.32). The improvement in aortic vascular inflammation in the TNFi group was independent of cardiovascular risk factors (adjusted ß = -0.41 [95% confidence interval -0.74, -0.08], P = 0.02). CONCLUSION: Our findings indicate that TNFi treatment is associated with reduced progression of carotid plaques in men and improvement in vascular inflammation in both men and women with psoriatic disease.


Subject(s)
Antirheumatic Agents/therapeutic use , Atherosclerosis/etiology , Plaque, Atherosclerotic/etiology , Psoriasis/drug therapy , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Adult , Aged , Atherosclerosis/diagnostic imaging , Atherosclerosis/drug therapy , Canada , Cohort Studies , Disease Progression , Female , Fluorodeoxyglucose F18 , Humans , Male , Middle Aged , Plaque, Atherosclerotic/diagnostic imaging , Plaque, Atherosclerotic/drug therapy , Positron Emission Tomography Computed Tomography/methods , Prospective Studies , Psoriasis/complications , Risk Factors
14.
Arthritis Rheumatol ; 68(5): 1060-71, 2016 05.
Article in English | MEDLINE | ID: mdl-26749174

ABSTRACT

OBJECTIVE: To update the 2009 Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) treatment recommendations for the spectrum of manifestations affecting patients with psoriatic arthritis (PsA). METHODS: GRAPPA rheumatologists, dermatologists, and PsA patients drafted overarching principles for the management of PsA, based on consensus achieved at face-to-face meetings and via online surveys. We conducted literature reviews regarding treatment for the key domains of PsA (arthritis, spondylitis, enthesitis, dactylitis, skin disease, and nail disease) and convened a new group to identify pertinent comorbidities and their effect on treatment. Finally, we drafted treatment recommendations for each of the clinical manifestations and assessed the level of agreement for the overarching principles and treatment recommendations among GRAPPA members, using an online questionnaire. RESULTS: Six overarching principles had ≥80% agreement among both health care professionals (n = 135) and patient research partners (n = 10). We developed treatment recommendations and a schema incorporating these principles for arthritis, spondylitis, enthesitis, dactylitis, skin disease, nail disease, and comorbidities in the setting of PsA, using the Grading of Recommendations, Assessment, Development and Evaluation process. Agreement of >80% was reached for approval of the individual recommendations and the overall schema. CONCLUSION: We present overarching principles and updated treatment recommendations for the key manifestations of PsA, including related comorbidities, based on a literature review and consensus of GRAPPA members (rheumatologists, dermatologists, other health care providers, and patient research partners). Further updates are anticipated as the therapeutic landscape in PsA evolves.


Subject(s)
Adrenal Cortex Hormones/therapeutic use , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Antirheumatic Agents/therapeutic use , Arthritis, Psoriatic/therapy , Physical Therapy Modalities , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Administration, Oral , Antibodies, Monoclonal/therapeutic use , Antibodies, Monoclonal, Humanized , Humans , Injections, Intra-Articular , Ustekinumab/therapeutic use
15.
Trends Biotechnol ; 34(1): 70-83, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26620970

ABSTRACT

Challenges in demonstrating interchangeability and safety, as well as the ongoing evolution of regulations governing biosimilars, have meant that the development of the biosimilars industry has not been, and will not be, a carbon copy of the generics industry. Complexity in the development process reduces the cost advantages for biosimilars that generics offer over originators. There has been a marked difference in the number of biosimilars approved by the European Medicines Agency (EMA) and US FDA due to a lack of consensus and the different rates of progress in establishing both law and stable evidence-based regulatory guidelines for biosimilars. In this review, we provide a précis of the history and status of the regulatory regimes in the USA and Europe. Included is an assessment of market and nonmarket factors that may continue to influence the development of the biosimilars industry.


Subject(s)
Biosimilar Pharmaceuticals , Drug Industry/legislation & jurisprudence , Legislation, Drug/trends
16.
Curr Opin Rheumatol ; 27(2): 111-7, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25603036

ABSTRACT

PURPOSE OF REVIEW: Enthesitis and dactylitis are cardinal manifestations of psoriatic arthritis (PsA), but a limited understanding of underlying pathophysiologic mechanisms has hindered development of targeted therapies. This gap is of clinical relevance because these manifestations are clinically relevant to patients. Herein, we discuss new exciting findings in animal models with enthesitis and dactylitis, summarize developments in clinical and imaging assessments and review recent clinical trial data on the efficacy of targeted therapies for enthesitis and dactylitis. RECENT FINDINGS: Several different animal models reveal that cytokines in the interleukin-23/Th17 pathway and mechanical stress are key events in the development of enthesitis and dactylitis. Elevated levels of interleukin-23, generated in the gut, joint or skin, trigger subsequent tissue inflammation. Both enthesitis and dactylitis involve heterogeneous tissues, associate with specific Class I Major Histocompatibility Complex alleles, and enthesitis may be critical for the development of PsA, although a causal pathway remains unproven. Diagnosis is based on clinical and imaging assessments; however, Power Doppler ultrasound (PDUS) is more sensitive for diagnosis and longitudinal follow-up of enthesitis. Agents targeting tumor necrosis factor, interleukin-12/23, interleukin-17, interleukin-17 receptor (interleukin-17R) and PDE4 are effective therapies for psoriatic enthesitis and dactylitis. SUMMARY: Novel preclinical models established, for the first time, the importance of the interleukin-23/Th17 pathway and mechanical stress in pathogenesis of dactylitis and enthesitis. Advances in imaging, particular (PDUS), may improve sensitivity and specificity for diagnosis and longitudinal assessments. Many targeted therapies are effective for enthesitis and dactylitis.


Subject(s)
Arthritis, Psoriatic/complications , Fingers , Tendinopathy/etiology , Animals , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Arthritis, Psoriatic/immunology , Cytokines/immunology , Disease Models, Animal , Humans , Mice , Tendinopathy/diagnosis , Tendinopathy/drug therapy , Tendinopathy/immunology
17.
J Rheumatol ; 41(11): 2290-4, 2014 Nov.
Article in English | MEDLINE | ID: mdl-25362713

ABSTRACT

Enthesitis is a characteristic feature of psoriatic arthritis (PsA) and is important in disease pathogenesis and classification. Use of clinical outcome measures for enthesitis is heterogeneous, and only 1 measure has been specifically developed and validated in PsA. Ultrasound and magnetic resonance imaging assessments of enthesitis may have advantages over clinical examination but are insufficiently studied. As part of an update of treatment recommendations by the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA), we performed a systematic literature review and identified randomized controlled trials with enthesitis outcomes in PsA. For each treatment agent we calculated treatment effect sizes (where applicable) and graded the level of evidence.


Subject(s)
Antirheumatic Agents/administration & dosage , Arthritis, Psoriatic/drug therapy , Practice Guidelines as Topic , Rheumatic Diseases/diagnosis , Rheumatic Diseases/drug therapy , Adrenal Cortex Hormones/therapeutic use , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Arthritis, Psoriatic/diagnosis , Biological Products/therapeutic use , Female , Humans , Joint Capsule/drug effects , Joint Capsule/physiopathology , Ligaments, Articular/drug effects , Ligaments, Articular/physiopathology , Male , Prognosis , Randomized Controlled Trials as Topic , Risk Assessment , Severity of Illness Index , Societies, Medical/standards , Tendinopathy/drug therapy , Tendinopathy/physiopathology , Treatment Outcome
18.
Arthritis Res Ther ; 16(4): R161, 2014 Jul 30.
Article in English | MEDLINE | ID: mdl-25078679

ABSTRACT

INTRODUCTION: Psoriasis and psoriatic arthritis (PsA) increase cardiovascular disease (CVD) risk, but surrogate markers for CVD in these disorders are inadequate. Because the presence of sacroiliitis may portend more severe PsA, we hypothesized that sacroiliitis defined by computed tomography (CT) would be associated with increased vascular inflammation defined by 18-fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT), which is an established measure of CVD. METHODS: Participants (n = 65) underwent whole-body FDG-PET/CT. Metabolic activity of the aorta was measured using the maximal standardized uptake value (SUVmax), a measure of atherosclerotic plaque activity. The primary outcome was aortic vascular inflammation. Linear regression (with ß-coefficients (ß) and P-values reported for PsA and sacroiliitis) was used to adjust for CVD risk factors to determine associations of PsA or sacroiliitis with vascular inflammation. Likelihood ratio testing was performed to evaluate the contribution of sacroiliitis to vascular disease estimation compared to the effects of PsA and traditional CVD risk factors. RESULTS: Vascular inflammation (measured as SUVmax) was greater (P < 0.001) in patients with sacroiliitis (mean ± SD = 7.33 ± 2.09) defined by CT compared to those without sacroiliitis (6.39 ± 1.49, P = 0.038). There were associations between PsA and aortic inflammation (ß = 0.124, P < 0.001) and between sacroiliitis and aortic inflammation (ß = 0.270, P < 0.001) after adjusting for CVD risk factors. Sacroiliitis predicted vascular inflammation beyond PsA and CVD risk factors (χ2 = 124.6, P < 0.001). CONCLUSIONS: Sacroiliitis is associated with increased vascular inflammation detected by FDG-PET/CT, suggesting that sacroiliac joint disease may identify patients at greater risk for CVD. Large, ongoing prospective studies are required to confirm these findings.


Subject(s)
Aortitis/diagnostic imaging , Arthritis, Psoriatic/diagnostic imaging , Sacroiliitis/diagnostic imaging , Adult , Aged , Aortitis/etiology , Arthritis, Psoriatic/complications , Female , Fluorodeoxyglucose F18 , Humans , Male , Middle Aged , Multimodal Imaging , Positron-Emission Tomography , Radiopharmaceuticals , Risk Factors , Sacroiliitis/complications , Tomography, X-Ray Computed
19.
Semin Arthritis Rheum ; 43(4): 577, 2014 Feb.
Article in English | MEDLINE | ID: mdl-24485351

ABSTRACT

The challenge of providing uniformly effective rheumatoid arthritis care has thus far defied a simple solution. Variations in care range from the appropriate adjustment or switching of therapy subsequent to increased disease activity to the selection of therapeutic agent chosen following failure. This program is designed to improve the understanding of advances in immunopathologic discoveries that provide valuable aid in individualized treatment plans and the appropriate patient selection of available DMARDS and biologic therapeutics. Also, expert rheumatologists will discuss the latest data of head-to-head trials and recommendations for clinical effectiveness. This CME program will bring rheumatologists and other health care professionals up to date in managing their patients with rheumatoid arthritis.


Subject(s)
Antirheumatic Agents/therapeutic use , Arthritis, Rheumatoid/drug therapy , Biological Products/therapeutic use , Humans
20.
Stem Cells Transl Med ; 1(12): 909-20, 2012 Dec.
Article in English | MEDLINE | ID: mdl-23283552

ABSTRACT

A wide range of regulatory standards applicable to production and use of tissues, cells, and other biologics (or biologicals), as advanced therapies, indicates considerable interest in the regulation of these products. The objective of this study was to analyze and compare high-tier documents within the Australian, European, and U.S. biologic drug regulatory environments using qualitative methodology. Eighteen high-tier documents from the European Medicines Agency (EMA), U.S. Food and Drug Administration (FDA), and Therapeutic Goods Administration (TGA) regulatory frameworks were subject to automated text analysis. Selected documents were consistent with the legal requirements for manufacturing and use of biologic drugs in humans and fall into six different categories. Concepts, themes, and their co-occurrence were identified and compared. The most frequent concepts in TGA, FDA, and EMA frameworks were "biological," "product," and "medicinal," respectively. This was consistent with the previous manual terminology search. Good Manufacturing Practice documents, across frameworks, identified "quality" and "appropriate" as main concepts, whereas in Good Clinical Practice (GCP) documents it was "clinical," followed by "trial," "subjects," "sponsor," and "data." GCP documents displayed considerably higher concordance between different regulatory frameworks, as demonstrated by a smaller number of concepts, similar size, and similar distance between them. Although high-tier documents often use different terminology, they share concepts and themes. This paper may be a modest contribution to the recognition of similarities and differences between analyzed regulatory documents. It may also fill the literature gap and provide some foundation for future comparative research of biologic drug regulations on a global level.


Subject(s)
Documentation/standards , Software/standards , Stem Cell Transplantation/legislation & jurisprudence , Stem Cell Transplantation/standards , United States Food and Drug Administration/legislation & jurisprudence , United States Food and Drug Administration/standards , Animals , Australia , Biological Products/standards , Europe , Humans , Terminology as Topic , United States
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