Lichen Planus

Lichen planus (LP) is a T cell-mediated disease affecting the stratified squamous epithelia of the skin and/or mucus membrane. Histologically, the disease is characterized by a lichenoid inflammatory infiltrate and vacuolar degeneration of the basal layer of the epidermis. LP has three major subtypes: Cutaneous, mucosal and appendageal LP. Rarely, it may affect the nails in the absence of skin and/or mucosal changes. LP may also be induced by several drugs, typically anti-hypertensive medication or be associated with infections, particularly viral hepatitis. The diagnosis is based on the clinical presentation and characteristic histological findings. Although the disease is often self-limiting, the intractable pruritus and painful mucosal erosions result in significant morbidity. The current first-line treatment are topical and/or systemic corticosteroids. In addition, immunosuppressants may be used as corticosteroid-sparing agents. These, however are often not sufficient to control disease. Janus kinase inhibitors and biologics (anti-IL-12/23, anti-IL17) have emerged as novel future treatment options. Thus, one may expect a dramatic change of the treatment landscape of LP in the near future.

Download Full-text

Emerging strategies in peripheral T-cell lymphoma

Hematology ◽

10.1182/hematology.2019000012 ◽

2019 ◽

Vol 2019 (1) ◽

pp. 41-46

Author(s):

Neha Mehta-Shah

Keyword(s):

T Cell ◽

Kinase Inhibitors ◽

Residual Disease ◽

Treatment Options ◽

Brentuximab Vedotin ◽

Janus Kinase ◽

Combination Strategies ◽

T Cell Lymphomas ◽

Personalized Approach ◽

Overall Survival Benefit

Abstract Peripheral T-cell lymphomas (PTCLs) are a heterogenous group of aggressive non-Hodgkin lymphomas that are less chemosensitive than their B-cell counterparts. Until recently, standard therapy did not distinguish between subtypes, and deeper understanding of the biology of these diseases was lacking. The availability of targeted therapy and more sophisticated subtype classification has translated into the development of novel treatment options for these rare diseases. This includes the development of a brentuximab vedotin-based upfront chemotherapy regimen that confers an overall survival benefit for a subset of patients. Clinical trials of targeted agents, as well as development of better preclinical models of PTCL, are leading to therapeutic advances in the field, including the development of phosphoinositide-3-kinase inhibitors, histone deacetylase inhibitor-based strategies, CD30-directed strategies, Janus kinase inhibitors, and spleen-associated tyrosine kinase inhibitors. Better understanding of the biology of these diseases based on gene expression profiling, minimal residual disease evaluation, and modeling in patient-derived xenografts should help define mechanisms of response and resistance to therapy. Given the complex biology of these heterogeneous lymphomas, well-tolerated combination strategies targeted toward specific subtypes of PTCL can lead to advances in the field. Similar to the story of brentuximab vedotin, development of effective therapies in the salvage setting will likely lead to improved upfront strategies in PTCLs, and ultimately a more personalized approach.

Download Full-text

Integrative transcriptome analyses empower the anti-COVID-19 drug arsenal

10.21203/rs.3.rs-37528/v1 ◽

2020 ◽

Author(s):

Nehme El-Hachem ◽

Edward Eid ◽

Georges Nemer ◽

Ghassan Dbaibo ◽

Nelly Rubeiz ◽

...

Keyword(s):

Kinase Inhibitors ◽

Clinical Investigation ◽

Expression Profiles ◽

Treatment Options ◽

Janus Kinase ◽

Normal Lung ◽

Drug Induced ◽

Significant Treatment ◽

Treatment Protocols ◽

Pharmaceutical Industries

Abstract The beginning of the twenty-first century has been marked by three distinct waves of zoonotic coronavirus outbreaks into the human population. The current pandemic COVID-19 (Coronavirus disease 2019) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). With a rapid infection rate, it is a global threat endangering the livelihoods of millions worldwide. Currently, and despite the collaborative efforts of governments, researchers, and the pharmaceutical industries, there are no substantially significant treatment protocols for the disease. To address the need for such an immediate call of action, we leveraged the largest dataset of drug-induced transcriptomic perturbations, public SARS-CoV-2 transcriptomic datasets, and expression profiles from normal lung transcriptomes. Our unbiased systems biology approach not only shed light on previously unexplored molecular details of SARS-CoV-2 infection (e.g., interferon signaling, inflammation and ACE2 co-expression hallmarks in normal and infected lungs) but most importantly prioritized more than 50 repurposable drug candidates (e.g., Corticosteroids, Janus kinase and Bruton kinase inhibitors). Further clinical investigation of these FDA approved candidates as monotherapy or in combination with an antiviral regimen (e.g., Remdesivir) could be promising treatment options against COVID-19.

Download Full-text

Comparative effectiveness of antitumour necrosis factor agents, biologics with an alternative mode of action and tofacitinib in an observational cohort of patients with rheumatoid arthritis in Switzerland

RMD Open ◽

10.1136/rmdopen-2020-001174 ◽

2020 ◽

Vol 6 (1) ◽

pp. e001174 ◽

Cited By ~ 2

Author(s):

A Finckh ◽

C Tellenbach ◽

L Herzog ◽

A Scherer ◽

B Moeller ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Kinase Inhibitors ◽

Treatment Options ◽

Clinical Effectiveness ◽

Janus Kinase ◽

Alternative Mode ◽

Janus Kinase Inhibitors ◽

Younger Age ◽

Observational Cohort ◽

Synthetic Dmards

BackgroundMultiple biologic and targeted synthetic disease-modifying rheumatic drugs (b/tsDMARDs) are approved for the management of rheumatoid arthritis (RA), including TNF inhibitors (TNFi), bDMARDs with other modes of action (bDMARD-OMA) and Janus kinase inhibitors (JAKi). Combination of b/tsDMARDs with conventional synthetic DMARDs (csDMARDs) is recommended, yet monotherapy is common in practice.ObjectiveTo compare drug maintenance and clinical effectiveness of three alternative treatment options for RA management.MethodsThis observational cohort study was nested within the Swiss RA Registry. TNFi, bDMARD-OMA (abatacept or anti-IL6 agents) or the JAKi tofacitinib (Tofa) initiated in adult RA patients were included. The primary outcome was overall drug retention. We further analysed secondary effectiveness outcomes and whether concomitant csDMARDs modified effectiveness, adjusting for potential confounding factors.Results4023 treatment courses of 2600 patients were included, 1862 on TNFi, 1355 on bDMARD-OMA and 806 on Tofa. TNFi was more frequently used as a first b/tsDMARDs, at a younger age and with shorter disease duration. Overall drug maintenance was significantly lower with TNFi compared with Tofa [HR 1.29 (95% CI 1.14 to 1.47)], but similar between bDMARD-OMA and Tofa [HR 1.09 (95% CI 0.96 to 1.24)]. TNFi maintenance was decreased when prescribed without concomitant csDMARDs [HR: 1.27 (95% CI 1.08 to 1.49)], while no difference was observed for bDMARD-OMA or Tofa maintenance with respect to concomitant csDMARDs.ConclusionTofa drug maintenance was comparable with bDMARDs-OMA and somewhat higher than TNFi. Concomitant csDMARDs appear to be required for optimal effectiveness of TNFi, but not for bDMARD-OMA or Tofa.

Download Full-text

An Update for Pharmacologists on New Treatment Options for Inflammatory Bowel Disease: The Clinicians’ Perspective

Frontiers in Pharmacology ◽

10.3389/fphar.2021.655054 ◽

2021 ◽

Vol 12 ◽

Author(s):

Carsten Schmidt ◽

Philip C. Grunert ◽

Andreas Stallmach

Keyword(s):

Inflammatory Bowel Disease ◽

Bowel Disease ◽

Kinase Inhibitors ◽

Treatment Options ◽

Drug Efficacy ◽

Janus Kinase ◽

Current State ◽

Sphingosine 1 Phosphate ◽

Inflammatory Bowel ◽

New Treatment

The introduction of anti-tumor necrosis factor antibodies resulted in a considerable expansion of the options available for the treatment of inflammatory bowel disease. Unfortunately, approximately one third of treated patients do not respond to these modalities, and drug efficacy may be lost over time. These drugs are also associated with contraindications, adverse events, and intolerance. As such, there is an ongoing need for new therapeutic strategies. Despite several recent advances, including antibodies against pro-inflammatory cytokines and cell adhesion molecules, Janus kinase inhibitors, and modulators of sphingosine-1-phosphate receptors, not all problems associated with IBD have been solved. In this manuscript, we review the current state of development of several new treatment options. Ongoing evaluation will require specific proof of efficacy as well as direct comparisons with established treatments. Results from head-to-head comparisons are needed to provide clinicians with critical information on how to formulate effective therapeutic approaches for each patient.

Download Full-text

Experience with ruxolitinib in the treatment of polycythaemia vera

Therapeutic Advances in Hematology ◽

10.1177/2040620717693972 ◽

2017 ◽

Vol 8 (4) ◽

pp. 139-151 ◽

Cited By ~ 6

Author(s):

Samah Alimam ◽

Claire Harrison

Keyword(s):

High Risk ◽

Kinase Inhibitors ◽

Treatment Options ◽

Myeloproliferative Neoplasm ◽

Jak2 V617f ◽

Janus Kinase ◽

Polycythaemia Vera ◽

Thromboembolic Events ◽

Childbearing Age ◽

Related Complication

Polycythaemia vera (PV) is a myeloproliferative neoplasm classically characterized by an erythrocytosis and is associated with a high risk of thromboembolic events, constitutional symptoms burden and risk of transformation to myelofibrosis and acute myeloid leukaemia. Therapy is directed at the haematocrit (HCT) to reduce the risk of thrombotic events and usually comprises low-dose aspirin and phlebotomy to maintain HCT at >45%. Frequently in addition, cytoreductive therapy is indicated in high-risk patients for normalizing haematological parameters to mitigate the occurrence of thromboembolic events. Unfortunately, there is no clear evidence that current therapies reduce the risk of transformation to myelofibrosis and for some a risk of a therapy related complication is unknown for example leukaemia due to hydroxycarbamide (HC). First-line therapy for treating PV remains HC or interferon, the latter most often in younger patients, especially those of childbearing age. However, therapy related intolerance or resistance is a common feature and results in limited treatment options for such patients. The discovery of the JAK2 V617F mutation and consequently targeted therapy with Janus kinase inhibitors, in particular ruxolitinib, has extended the spectrum of agents that can be used as second or third line in PV. The findings of the phase II trial RESPONSE and the preliminary data from RESPONSE 2 trial have identified a role for ruxolitinib in PV patients who are resistant or intolerant to HC. In this article, using clinical cases we demonstrate our experience with ruxolitinib highlighting the clinical benefits and limitations we encountered in clinical practice.

Download Full-text

Hijaking the SARS-CoV-2 Cytokinopathy: Janus Kinase Inhibitors for Moderate to Severe COVID-19

SSRN Electronic Journal ◽

10.2139/ssrn.3606658 ◽

2020 ◽

Author(s):

Christine Won ◽

William Damsky ◽

Inderjit Singh ◽

Phillip Joseph ◽

Astha Chichra ◽

...

Keyword(s):

Kinase Inhibitors ◽

Janus Kinase ◽

Janus Kinase Inhibitors

Download Full-text

Characteristics and Treatment Challenges of Non-Clear Cell Renal Cell Carcinoma

Cancers ◽

10.3390/cancers13153807 ◽

2021 ◽

Vol 13 (15) ◽

pp. 3807

Author(s):

Pierangela Sepe ◽

Arianna Ottini ◽

Chiara Carlotta Pircher ◽

Andrea Franza ◽

Melanie Claps ◽

...

Keyword(s):

Renal Cell ◽

Kinase Inhibitors ◽

Clear Cell ◽

Case Reports ◽

Treatment Options ◽

Single Agent ◽

Growth Factor Receptor ◽

Mtor Inhibitors ◽

Cell Renal Cell Carcinoma ◽

Clear Cell Rcc

Non-clear cell renal cell carcinomas (RCC) comprise several rare and poorly described diseases, often characterized by bad prognosis and with no standard treatments available. The gap in their clinical management is linked to the poor molecular characterization in handling the treatment of non clear-cell RCC with untailored therapies. Due to their rarity, non-clear RCC are in fact under-represented in prospective randomized trials. Thus, treatment choices are based on extrapolating results from clear cell RCC trials, retrospective data, or case reports. Over the last two decades, various options have been considered as the mainstay for the treatment of metastatic RCC (mRCC), including angiogenesis inhibitors, vascular endothelial growth factor receptor inhibitors, other tyrosine kinase inhibitors (TKIs), as well as MET inhibitors and mammalian targeting of rapamycin (mTOR) inhibitors. More recently, the therapeutic armamentarium has been enriched with immunotherapy, alone or in combination with targeted agents that have been shown to significantly improve outcomes of mRCC patients, if compared to TKI single-agent. It has been widely proven that non-clear cell RCC is a morphologically and clinically distinct entity from its clear cell counterpart but more knowledge about its biology is certainly needed. Histology-specific collaborative trials are in fact now emerging to investigate different treatments for non-clear cell RCC. This review summarizes pathogenetic mechanisms of non-clear cell RCC, the evolution of treatment paradigms over the last few decades, with a focus on immunotherapy-based trials, and future potential treatment options.

Download Full-text