Perkembangan Terkini Terapi Sistemik Psoriasis

Natalia Rania Sutanto; Windy Keumala Budianti

doi:10.36452/jkdoktmeditek.v27i2.2043

Perkembangan Terkini Terapi Sistemik Psoriasis

Jurnal Kedokteran Meditek ◽

10.36452/jkdoktmeditek.v27i2.2043 ◽

2021 ◽

Vol 27 (2) ◽

pp. 136-146

Author(s):

Natalia Rania Sutanto ◽

Windy Keumala Budianti

Keyword(s):

Small Molecules ◽

Tnf Α

Psoriasis merupakan penyakit inflamasi kulit akibat aktivasi terhadap sistem imun bawaan dan adaptif. Etiopatogenesis psoriasis merupakan proses kompleks dan multifaktorial, yang dipengaruhi oleh faktor genetik dan lingkungan seperti stres, trauma, dan infeksi. Pada pasien dengan psoriasis kategori sedang hingga berat dan lesi lokalisata di area skalp, wajah, kuku, telapak tangan dan kaki, serta genital merupakan indikasi untuk pemberian terapi dengan obat sistemik. Saat ini terdapat berbagai pilihan terapi sistemik yang tersedia yaitu obat sistemik konvensional, terapi small molecules, obat biologik, dan biosimilarnya yang terdiri atas inhibitor TNF-α, inhibitor IL-12/23, inhibitor IL-17, dan inhibitor IL-23. Selama dekade terakhir, tata laksana psoriasis telah mengalami pergeseran paradigma yaitu obat biologik dan biosimilarnya mulai menjadi pilihan utama karena telah terbukti memiliki efektivitas baik, dengan efek samping minimal. Tinjauan pustaka ini membahas perkembangan terapi sistemik psoriasis terkini sehingga diharapkan dapat memberikan acuan untuk memilih terapi yang tepat, efektif, dan aman untuk pasien psoriasis.

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TNF-α: the shape of small molecules to come?

Drug Discovery Today ◽

10.1016/j.drudis.2021.06.018 ◽

2021 ◽

Author(s):

Alexander Dömling ◽

Xin Li

Keyword(s):

Small Molecules ◽

Tnf Α ◽

To Come

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A New Application of Parallel Synthesis Strategy for Discovery of Amide-Linked Small Molecules as Potent Chondroprotective Agents in TNF-α-Stimulated Chondrocytes

PLoS ONE ◽

10.1371/journal.pone.0149317 ◽

2016 ◽

Vol 11 (3) ◽

pp. e0149317 ◽

Cited By ~ 3

Author(s):

Chia-Chung Lee ◽

Yang Lo ◽

Ling-Jun Ho ◽

Jenn-Haung Lai ◽

Shiu-Bii Lien ◽

...

Keyword(s):

Small Molecules ◽

Parallel Synthesis ◽

Synthesis Strategy ◽

Tnf Α

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Correction: A New Application of Parallel Synthesis Strategy for Discovery of Amide-Linked Small Molecules as Potent Chondroprotective Agents in TNF-α-Stimulated Chondrocytes

PLoS ONE ◽

10.1371/journal.pone.0154067 ◽

2016 ◽

Vol 11 (4) ◽

pp. e0154067

Author(s):

Keyword(s):

Small Molecules ◽

Parallel Synthesis ◽

Synthesis Strategy ◽

Tnf Α

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Baricitinib restrains the immune dysregulation in COVID-19 patients

10.1101/2020.06.26.20135319 ◽

2020 ◽

Cited By ~ 5

Author(s):

Vincenzo Bronte ◽

Stefano Ugel ◽

Elisa Tinazzi ◽

Antonio Vella ◽

Francesco De Sanctis ◽

...

Keyword(s):

Small Molecules ◽

Target Therapy ◽

Serum Levels ◽

Progressive Increase ◽

Good Prognosis ◽

Rapid Reduction ◽

Jak2 Inhibitor ◽

Immune Mediators ◽

Tnf Α ◽

Necrosis Factor

AbstractSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the ongoing pandemic coronavirus disease 2019 (COVID-19). The majority of patients with COVID-19 have a good prognosis, but variable percentages in different countries develop pneumonia associated with lymphocytopenia and severe inflammatory response due to uncontrolled release of cytokines. These immune mediators are transcriptionally regulated by JAK-STAT molecular pathways, which can be disabled by small molecules. Here, we provide evidences on the efficacy of baricitinib, a JAK1/JAK2 inhibitor, in correcting the immune abnormalities observed in patients hospitalized with COVID-19. Indeed, we demonstrate a significant reduction in serum levels of interleukin (IL)-6, IL-1β and tumor necrosis factor (TNF)α, a rapid recovery in circulating T and B cell frequencies and an increased antibody production against SARS-CoV-2 spike protein in baricitinib-treated patients. Moreover, treated patients underwent a rapid reduction in oxygen flow need and progressive increase in the P/F. Our work provides the basis on developing effective treatments against COVID-19 pathogenesis using on-target therapy.

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Efficacy of biological therapies and small molecules in moderate to severe ulcerative colitis: systematic review and network meta-analysis

Gut ◽

10.1136/gutjnl-2021-326390 ◽

2021 ◽

pp. gutjnl-2021-326390

Author(s):

Nicholas E Burr ◽

David J Gracie ◽

Christopher J Black ◽

Alexander C Ford

Keyword(s):

Ulcerative Colitis ◽

Adverse Events ◽

Small Molecules ◽

Clinical Remission ◽

Meta Analysis ◽

Biological Therapies ◽

Serious Adverse Events ◽

Once Daily ◽

Tnf Α ◽

Reported Data

ObjectiveBiological therapies and small molecules continue to be evaluated in moderate to severely active ulcerative colitis, but are often studied in placebo-controlled trials, meaning their relative efficacy and safety is unknown. We examined this in a network meta-analysis.DesignWe searched the literature to October 2021 to identify eligible trials. We judged efficacy using clinical remission, endoscopic improvement, or clinical response, and according to previous exposure or non-exposure to antitumour necrosis factor (TNF)-α therapy. We also assessed safety. We used a random effects model and reported data as pooled relative risks (RRs) with 95% CIs. Interventions were ranked according to their P-score.ResultsWe identified 28 trials (12 504 patients). Based on failure to achieve clinical remission, upadacitinib 45 mg once daily ranked first versus placebo (RR 0.73; 95% CI 0.68 to 0.80, P-score 0.98), with infliximab 5 mg/kg and 10 mg/kg second and third, respectively. Upadacitinib ranked first for clinical remission in both patients naïve to anti-TNF-α drugs (RR 0.69; 95% CI 0.61 to 0.78, P-score 0.99) and previously exposed (RR 0.78; 95% CI 0.72 to 0.85, P-score 0.99). Upadacitinib was superior to almost all other drugs in these analyses. Based on failure to achieve endoscopic improvement infliximab 10 mg/kg ranked first (RR 0.61; 95% CI 0.51 to 0.72, P-score 0.97), with upadacitinib 45 mg once daily, second, and infliximab 5 mg/kg third. Upadacitinib was more likely to lead to adverse events, but serious adverse events were no more frequent, and withdrawals due to adverse events were significantly lower than with placebo. Infections were significantly more likely with tofacitinib than placebo (RR 1.41; 95% CI 1.03 to 1.91).ConclusionIn a network meta-analysis, upadacitinib 45 mg once daily ranked first for clinical remission in all patients, patients naïve to anti-TNF-α drugs and patients previously exposed. Infliximab 10 mg/kg ranked first for endoscopic improvement. Most drugs were safe and well tolerated.

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Gap junctions in the prothoracic glands of the tobacco hornworm, Manduca sexta

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100123933 ◽

1992 ◽

Vol 50 (1) ◽

pp. 706-707

Author(s):

Ji-da Dai ◽

M. Joseph Costello ◽

Lawrence I. Gilbert

Keyword(s):

Gap Junctions ◽

Small Molecules ◽

Manduca Sexta ◽

Freeze Fracture ◽

Cell Communication ◽

Cellular Level ◽

Thin Sections ◽

Prothoracic Glands ◽

Polyhydroxylated Steroids ◽

Stimulation Of

Insect molting and metamorphosis are elicited by a class of polyhydroxylated steroids, ecdysteroids, that originate in the prothoracic glands (PGs). Prothoracicotropic hormone stimulation of steroidogenesis by the PGs at the cellular level involves both calcium and cAMP. Cell-to-cell communication mediated by gap junctions may play a key role in regulating signal transduction by controlling the transmission of small molecules and ions between adjacent cells. This is the first report of gap junctions in the PGs, the evidence obtained by means of SEM, thin sections and freeze-fracture replicas.

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Fusion and Fission Processes in Exocytosis: Possible Roles for Synexin and Osmotic Lysis in the Two Events

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s1431927600002634 ◽

1980 ◽

Vol 38 ◽

pp. 594-597

Author(s):

H.B. Pollard ◽

C.E. Creutz ◽

C.J. Pazoles ◽

J.H. Scott

Keyword(s):

Small Molecules ◽

Chromaffin Cells ◽

Adrenal Glands ◽

General Concept ◽

Extracellular Calcium ◽

Large Protein ◽

Granule Membrane ◽

Osmotic Lysis ◽

Per Se ◽

Chemical Evidence

Exocytosis is a general concept describing secretion of enzymes, hormones and transmitters that are otherwise sequestered in intracellular granules. Chemical evidence for this concept was first gathered from studies on chromaffin cells in perfused adrenal glands, in which it was found that granule contents, including both large protein and small molecules such as adrenaline and ATP, were released together while the granule membrane was retained in the cell. A number of exhaustive reviews of this early work have been published and are summarized in Reference 1. The critical experiments demonstrating the importance of extracellular calcium for exocytosis per se were also first performed in this system (2,3), further indicating the substantial service given by chromaffin cells to those interested in secretory phenomena over the years.

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Elevated level of circulatory sTLT1 induces inflammation through SYK/MEK/ERK signalling in coronary artery disease

Clinical Science ◽

10.1042/cs20190999 ◽

2019 ◽

Vol 133 (22) ◽

pp. 2283-2299

Author(s):

Apabrita Ayan Das ◽

Devasmita Chakravarty ◽

Debmalya Bhunia ◽

Surajit Ghosh ◽

Prakash C. Mandal ◽

...

Keyword(s):

Risk Factors ◽

Coronary Artery Disease ◽

Coronary Artery ◽

Chronic Inflammation ◽

Ex Vivo ◽

Human Subjects ◽

Critical Role ◽

Atherosclerotic Cardiovascular Disease ◽

Tnf Α ◽

Artery Disease

Abstract The role of inflammation in all phases of atherosclerotic process is well established and soluble TREM-like transcript 1 (sTLT1) is reported to be associated with chronic inflammation. Yet, no information is available about the involvement of sTLT1 in atherosclerotic cardiovascular disease. Present study was undertaken to determine the pathophysiological significance of sTLT1 in atherosclerosis by employing an observational study on human subjects (n=117) followed by experiments in human macrophages and atherosclerotic apolipoprotein E (apoE)−/− mice. Plasma level of sTLT1 was found to be significantly (P<0.05) higher in clinical (2342 ± 184 pg/ml) and subclinical cases (1773 ± 118 pg/ml) than healthy controls (461 ± 57 pg/ml). Moreover, statistical analyses further indicated that sTLT1 was not only associated with common risk factors for Coronary Artery Disease (CAD) in both clinical and subclinical groups but also strongly correlated with disease severity. Ex vivo studies on macrophages showed that sTLT1 interacts with Fcɣ receptor I (FcɣRI) to activate spleen tyrosine kinase (SYK)-mediated downstream MAP kinase signalling cascade to activate nuclear factor-κ B (NF-kB). Activation of NF-kB induces secretion of tumour necrosis factor-α (TNF-α) from macrophage cells that plays pivotal role in governing the persistence of chronic inflammation. Atherosclerotic apoE−/− mice also showed high levels of sTLT1 and TNF-α in nearly occluded aortic stage indicating the contribution of sTLT1 in inflammation. Our results clearly demonstrate that sTLT1 is clinically related to the risk factors of CAD. We also showed that binding of sTLT1 with macrophage membrane receptor, FcɣR1 initiates inflammatory signals in macrophages suggesting its critical role in thrombus development and atherosclerosis.

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