No abstract
BackgroundInformation on the factors that influence treatment management decisions for psoriatic arthritis (PsA) is limited.ObjectiveOur objective was to evaluate the impact of clinical specialty setting and geographic region on the management of patients with PsA in the USA.MethodsLOOP 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.ResultsOf 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.ConclusionsThere 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.Electronic supplementary materialThe online version of this article (10.1007/s40257-019-00470-6) contains supplementary material, which is available to authorized users.
Background Brodalumab is a fully human anti-interleukin-17 receptor A monoclonal antibody efficacious for the treatment of adults with moderate-to-severe plaque psoriasis. Objective This study summarizes malignancy rates in psoriasis clinical studies of brodalumab. Methods Data were pooled from one phase II study and three large, multicenter, phase III randomized studies of brodalumab for the treatment of psoriasis, including two studies with randomization to brodalumab, ustekinumab, or placebo. Data from the 52-week (brodalumab and ustekinumab) and long-term (brodalumab) pools were summarized as exposure-adjusted or follow-up time-adjusted event rates per 100 patient-years (PY). Results Exposure-adjusted event rates per 100 PY at 52 weeks were lower with brodalumab (n = 4019; 3446 total PY of exposure) than with ustekinumab (n = 613; 495 total PY of exposure), including adjudicated malignancies (0.9 vs 2.6) and Surveillance, Epidemiology, and End Results (SEER)-adjudicated malignancies (0.3 vs 0.4). The exposure-adjusted event rate of adjudicated malignancies in the brodalumab group remained stable in the long-term analysis (0.9 [82 events]). Conclusions Rates of malignancy among brodalumab-treated patients with psoriasis were generally low. Trial registry ClinicalTrials.gov identifier NCT00975637; NCT01101100; NCT01708590 (AMAGINE-1); NCT01708603 (AMAGINE-2); NCT01708629 (AMAGINE-3).
While biologic therapies for psoriasis are effective for many patients, some patients may lose response, have inadequate control of disease, or develop intolerance to certain biologic agents. It may therefore be beneficial for patients whose psoriasis fails to respond to one biologic to switch to a different biologic therapy, in particular one with a different mechanism of action. However, it remains unclear how prior biologic exposure or lack of response affects the efficacy and safety of subsequent biologics in patients with moderate-to-severe psoriasis.
A 60-year-old man presented to the Emergency Department (ED) with large, painful, indurated plaques on the right thigh, left abdomen, left chest, and right chest, which began without any preceding trauma on the right thigh 3 weeks prior to presentation in the ED. He was initially treated with cefazolin 1 g three times daily as home infusions. When the lesions continued to progress, he was admitted to the hospital and placed on amoxicillin/clavulanate and vancomycin. He had a single episode of fever of 102 degrees F, but his white blood cell count and differential remained normal. An initial biopsy showed a dermal inflammatory infiltrate composed primarily of neutrophils and eosinophils with rare flame figures in the dermis. There was minimal fat seen in this biopsy. A differential diagnosis of Wells or Sweet's syndrome was entertained, and he was placed on 60 mg/day prednisone with no resolution of his symptoms. The patient's past medical history included hypertension, hyperlipidemia, peripheral neuropathy, and hiatal hernia. His family history was significant for emphysema in both parents and coronary artery disease in his father. Both of his parents smoked cigarettes. His grandfather, who was a coal miner, also had emphysema. Whilst on antibiotics and prednisone, the plaques on the patient's right thigh, right abdomen, and left chest expanded and ulcerated, draining an oily liquid (Figs 1 and 2). An incisional biopsy was obtained from his thigh. Histopathology showed a septal and lobular panniculitis with fat necrosis, neutrophils, and histiocytes (Fig. 3). Special stains for organisms were negative. Tissue sent for bacterial and fungal culture had no growth. Amylase and lipase levels were normal. Rheumatoid factor, antinuclear antibody (ANA), antineutrophil cytoplasmic antibody (ANCA), cryoglobulins, and antiphospholipid antibodies were all normal. The alpha1-antitrypsin level was low at 25 mg/dL (ref. 75-135). The alpha1-antitrypsin phenotype was PiZZ. The patient had a normal glucose-6-phosphate dehydrogenase level and was placed on dapsone 200 mg/day. The inflammation resolved and, over the course of several months, the involved areas healed with scarring. The patient denied any pulmonary complaints but, during his hospitalization, was found incidentally to have an oxygen saturation of 88% on room air. He was sent for evaluation by a pulmonologist, and pulmonary function tests revealed a mixed restrictive and obstructive pattern with a forced expiratory volume in 1 to forced vital capacity (FEV(1)/FVC) ratio of 63% of predicted. He had never smoked. He was placed on supplemental oxygen but, as his pulmonary disease has been stable, he has not been treated with intravenous antitrypsin inhibitor.
We have recently shown that C5b-6 binds to the erythrocyte membrane via an ionic interaction with sialic acid before the addition of C7 and subsequent membrane insertion. In this study we assessed the role of anionic lipids in the binding of the terminal complement proteins to the membrane and the efficiency of subsequent hemolysis. Human erythrocytes were modified by insertion of dipalmitoyl phosphatidylcholine (DPPC), dipalmitoyl phosphatidylserine (DPPS), dipalmitoyl phosphatidylethanolamine (DPPE), or dipalmitoyl phosphatidic acid (DPPA). Lipid incorporation and the hemolytic assays were done in the presence of 100 μmol/L sodium orthovanadate to prevent enzymatic redistribution of lipid. We found that the neutral lipids, DPPC and DPPE, did not affect C5b-7 uptake or hemolysis by C5b-9. In contrast, the two acidic phospholipids, DPPS and DPPA, caused a dose-dependent increase in both lysis and C5b-7 uptake. We conclude that the presence of anionic lipids on the exterior face of the membrane increases C5b-7 uptake and subsequent hemolysis. It is known that sickle cell erythrocytes have increased exposure of phosphatidylserine on their external face and are abnormally sensitive to lysis by C5b-9. The data presented here provide a plausible mechanism for this increased sensitivity.
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