Management of moderate to severe psoriasis with brodalumab-Real-world evidence from the LIBERO study.

BACKGROUND: Brodalumab, a fully human monoclonal immunoglobulin IgG2 antibody that binds the human interleukin 17 receptor subunit A, is available for the treatment of moderate-to-severe plaque psoriasis in Europe since September 2017, but so far there are only a few studies on its use in real-world conditions. OBJECTIVES: To assess the management of moderate-to-severe psoriasis with brodalumab 210 mg in daily practice after 12 and 52 weeks (W). In addition, patient profiles and treatment pathways are described. METHODS: LIBERO is a prospective, multicenter, non-interventional study including adult patients with plaque psoriasis treated with brodalumab 210 mg. RESULTS: In total, 638 patients (65% male, mean age: 49.3 ± 14.4 years) from 148 sites in Germany were enrolled. The majority suffered from severe (51.1%) or very severe (13.1%) psoriasis according to physician global assessment (PGA0-5). When starting with brodalumab, 58.5% were biologic naïve and 41.5% were previously treated with another biologic, mainly adalimumab (18.5%) and secukinumab (17.9%). About 74.0% of patients met the primary endpoint of an absolute PASI ≤3 at ~W12 (n = 618, LOCF). The mean PASI was reduced significantly as of ~W2 from 17.2 (±11.7) to 9.7 (±8.8) and improved further to 3.3 (±6.3) at ~W12 (p < 0.001). At ~W52 85.5% of patients reached a PGA0/1-response (primary endpoint) and 54.1% patients were assessed as completely clear (PGA0) (both n = 399, as observed). Effectiveness of brodalumab was confirmed in relevant subgroup analysis by previous treatment regimen. Most frequently reported adverse events were nasopharyngitis (4.6%), psoriasis (4.6%) and arthralgia (4.1%), new safety signals were not detected. CONCLUSION: This representative, non-interventional study confirms the short- and long-term effectiveness and safety profile of brodalumab in the management of psoriasis in daily practice as well as in relevant treatment pathways.

Daily subcutaneous injections of peptide induce CD4+ CD25+ T regulatory cells.

Peptide immunotherapy is being explored to modulate varied disease states; however, the mechanism of action remains poorly understood. In this study, we investigated the ability of a subcutaneous peptide immunization schedule to induce of CD4(+) CD25(+) T regulatory cells. DO11.10 T cell receptor (TCR) transgenic mice on a Rag 2(-/-) background were injected subcutaneously with varied doses of purified ovalbumin (OVA(323-339)) peptide daily for 16 days. While these mice have no CD4(+) CD25(+) T regulatory cells, following this injection schedule up to 30% of the CD4(+) cells were found to express CD25. Real-time quantitative polymerase chain reaction (QPCR) analysis of the induced CD4(+) CD25(+) T cells revealed increased expression of forkhead box P3 (FoxP3), suggesting that these cells may have a regulatory function. Proliferation and suppression assays in vitro utilizing the induced CD4(+) CD25(+) T cells revealed a profound anergic phenotype in addition to potent suppressive capability. Importantly, co-injection of the induced CD4(+) CD25(+) T cells with 5,6-carboxy-succinimidyl-fluorescence-ester (CFSE)-labelled naive CD4(+) T cells (responder cells) into BALB/c recipient mice reduced proliferation and differentiation of the responder cells in response to challenge with OVA(323-339) peptide plus adjuvant. We conclude that repeated subcutaneous exposure to low-dose peptide leads to de novo induction of CD4(+) CD25(+) FoxP3(+) T regulatory cells with potent in vitro and in vivo suppressive capability, thereby suggesting that one mechanism of peptide immunotherapy appears to be induction of CD4(+) CD25(+) Foxp3(+) T regulatory cells.

[Morphology of diabetic neuropathy]. / Morphologie der diabetischen Neuropathie.

The morphological findings in peripheral nerves in diabetic subjects are reviewed. Diabetes is probably the most frequent cause of neuropathy. However it does not constitute a single nosological entity but is comprised of a variety of clinical and morphological changes. These are considered to be the consequences of metabolic derangements resulting from chronic hyperglycemia. Distal symmetrical neuropathies, which are most common, are characterized by axonal degeneration and segmental demyelination with loss of nerve fibres and fibrosis. Remyelination and axonal sprouting occur. Microvascular changes consist of thickening and hyalinization of the walls of the vessels. On electron microscopy these vessels appear thickened and show reduplication of the basal lamina that surrounds the endothelial cells and pericytes. The morphological bases of proximal symmetrical motor neuropathy, as well as of focal and multifocal neuropathies are briefly described. The synopsis of current knowledge can be helpful in diagnosis and differential diagnosis of disorders of the peripheral nervous system.

[Ultrastructural findings in testicular feminization]. / Ultrastrukturelle Befunde bei testikulärer Feminisierung.

On the basis of light and electron microscopic findings problems of the morphology of gonads in testicular feminization syndrome (TF) are discussed. Within the tubules 3 cell types (light, dark, intermediate) can be distinguished which are regarded as different functional forms of Sertoli cells. Germ cells were not observed definitely. There are, however, remarkable difficulties in morphological distinction between undifferentiated Sertoli and germ cells. It is underlined that fine structure of gonads and cellular composition of tubules as well as the amount of interstitial cells depend on the age of the individuum and on the form of TF (complete and incomplete).