The Use of Janus Kinase Inhibitors in Vitiligo: A Review of the Literature

2019 ◽  
Vol 23 (3) ◽  
pp. 298-306 ◽  
Author(s):  
Nicole Relke ◽  
Melinda Gooderham
Keyword(s):  
Kinase Inhibitors ◽  
Case Reports ◽  
Normal Skin ◽  
Unmet Need ◽  
Case Series ◽  
Janus Kinase ◽  
Jak Inhibitors ◽  
Open Label ◽  
Attractive Therapeutic Target ◽  
Favorable Safety

Vitiligo is a common acquired depigmenting disorder characterized by the development of white macules and patches due to the loss of melanocytes. Patients with vitiligo can be stigmatized by society, making the disease a source of psychological stress that can considerably affect quality of life. The goal of vitiligo treatment is to obtain skin repigmentation in the majority of cases, and less commonly to depigment the remaining normal skin. There is no consistent, long-term, durable therapy for vitiligo for all patients, highlighting the unmet need for new safe and effective therapies to control this disease. Recently, JAK inhibitors have been explored as a promising novel treatment option in vitiligo. The JAK and signal transducers and activators of transcription (STAT) pathway is an attractive therapeutic target because IFN-γ–dependent cytokines produced through this pathway have been implicated in the pathogenesis of disease. This literature review describes vitiligo pathophysiology, explains the usefulness of the JAK inhibitors for treatment, and summarizes published case reports, case series, and open-label studies. Research outlined here shows JAK inhibitors in patients with vitiligo have a favorable safety profile and effectively produce repigmentation of lesions, especially with concomitant ultraviolet exposure. Additional studies are required to confirm efficacy, establish safety, and investigate durability of repigmentation.

The Use of Janus Kinase Inhibitors in Alopecia Areata: A Review of the Literature

2019 ◽  
Vol 23 (3) ◽  
pp. 289-297 ◽  
Author(s):  
Erika L. Crowley ◽  
Shamone C. Fine ◽  
Kathleen Kwan Katipunan ◽  
Melinda J. Gooderham
Keyword(s):  
Case Studies ◽  
Health Care Providers ◽  
Alopecia Areata ◽  
Kinase Inhibitors ◽  
Case Reports ◽  
Case Series ◽  
Janus Kinase ◽  
Care Providers ◽  
Jak Inhibitors ◽  
Open Label

Alopecia areata (AA) is a chronic, immune-mediated disorder that targets hair follicle epithelium, thereby restricting hair growth in localized patches. Although several therapies for AA have been tested, responses with traditional therapies have been limited. In recent years, numerous reports have been published of patients with AA responding to Janus kinase (JAK) inhibitors. This literature review aims to describe AA pathophysiology, explore how and why JAK inhibitors can be used for AA treatment, and review published case reports, case series, and open-label studies published to date. Pathogenesis of AA includes interactions between genetic, environmental, and immune factors and is mediated by the cytokines interferon-γ and interleukin (IL)-15. JAK inhibition resulting in hair regrowth in some cases supports that AA is associated with the Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathway. The emergence of JAK inhibitors for AA therapy is changing the way health care providers think about and treat AA. A mixture of animal model studies and human case studies have reported the use of baricitinib (JAK 1/2), ruxolitinib (JAK 1/2), and tofacitinib (JAK 1/3) for the management of AA. JAK inhibition has shown potential as an effective AA therapy when used in case studies, case series, and open-label trials. Formal clinical trials are ongoing and will yield more definitive conclusions about the safety and efficacy of JAK inhibitors.

scholarly journals A Novel Hope for Alopecia Totalis Patients: Case Report

2020 ◽  
Vol 3 (4) ◽  
pp. 150-153
Author(s):  
Manal Elsayed ◽  
Laila Al Otaibi ◽  
Nael Quraishy ◽  
Afzalhussein Yusufali
Keyword(s):  
Case Report ◽  
Adverse Effects ◽  
Case Reports ◽  
Autoimmune Disorder ◽  
Juvenile Chronic Arthritis ◽  
Janus Kinase ◽  
Treatment Modalities ◽  
Jak Inhibitors ◽  
Open Label ◽  
Hair Regrowth

Alopecia areata (AA) is a common autoimmune disorder causing nonscarring patchy hair loss. Alopecia totalis (AT) is a severe variant of AA. Although there are several available treatment modalities for AA, efficacy of most of them is not satisfactory in case of AT. Recently, several case reports and series and small open-label studies have shown efficacy of oral Janus kinase (JAK) inhibitors as treatment for AT. Tofacitinib is one of the JAK inhibitors, which is an approved drug for treatment of rheumatoid and psoriatic arthritis. In this case report, we have treated a 24-year-old girl who had juvenile chronic arthritis and developed AT. She was treated for 3 years with different modalities without satisfactorily results. We treated her with tofacitinib 5 mg orally twice a day and assessed its efficacy and adverse effects if any. We monitored scalp hair regrowth of the patient using the score of severity of alopecia tool. The patient tolerated the treatment well; hair regrowth started from the 4th week and full regrowth attained by the 9th month of the treatment. No serious adverse effects were noticed. Tofacitinib can potentially be considered as an effective and well-tolerated treatment for AT; however, larger studies are needed to address its long-term efficacy.

scholarly journals Janus Kinase Inhibitors and Coronavirus Disease (COVID)-19: Rationale, Clinical Evidence and Safety Issues

2021 ◽  
Vol 14 (8) ◽  
pp. 738
Author(s):  
Milo Gatti ◽  
Eleonora Turrini ◽  
Emanuel Raschi ◽  
Piero Sestili ◽  
Carmela Fimognari
Keyword(s):  
Clinical Evidence ◽  
Kinase Inhibitors ◽  
Invasive Mechanical Ventilation ◽  
Supplemental Oxygen ◽  
Janus Kinase ◽  
European Medicines Agency ◽  
Jak Inhibitors ◽  
Open Label ◽  
Safety Issues ◽  
Hospitalised Patients

We are witnessing a paradigm shift in drug development and clinical practice to fight the novel coronavirus disease (COVID-19), and a number of clinical trials have been or are being testing various pharmacological approaches to counteract viral load and its complications such as cytokine storm. However, data on the effectiveness of antiviral and immune therapies are still inconclusive and inconsistent. As compared to other candidate drugs to treat COVID-19, Janus Kinase (JAK) inhibitors, including baricitinib and ruxolitinib, possess key pharmacological features for a potentially successful repurposing: convenient oral administration, favorable pharmacokinetic profile, multifunctional pharmacodynamics by exerting dual anti-inflammatory and anti-viral effects. Baricitinib, originally approved for rheumatoid arthritis, received Emergency Use Authorization in November 2020 by the Food and Drug Administration in combination with remdesivir for the treatment of COVID-19 in hospitalized patients ≥ 2 years old who require supplemental oxygen, invasive mechanical ventilation, or extracorporeal membrane oxygenation. By July 2021, the European Medicines Agency is also expected to issue the opinion on whether or not to extend its use in hospitalised patients from 10 years of age who require supplemental oxygen. Ruxolitinib, approved for myelofibrosis, was prescribed in patients with COVID-19 within an open-label Emergency Expanded Access Plan. This review will address key milestones in the discovery and use of JAK inhibitors in COVID-19, from artificial intelligence to current clinical evidence, including real world experience, and critically appraise emerging safety issues, namely infections, thrombosis, and liver injury. An outlook to ongoing studies (clinicaltrials.gov) and unpublished pharmacovigilance data is also offered.

Successful treatment of arthritis induced by checkpoint inhibitors with tocilizumab: a case series

2017 ◽  
Vol 76 (12) ◽  
pp. 2061-2064 ◽  
Author(s):  
Sang Taek Kim ◽  
Jean Tayar ◽  
Van Anh Trinh ◽  
Maria Suarez-Almazor ◽  
Salvador Garcia ◽  
...  
Keyword(s):  
Checkpoint Inhibitors ◽  
Case Reports ◽  
Unmet Need ◽  
Case Series ◽  
Receptor Antibody ◽  
Improved Outcomes ◽  
Clinical Scenarios ◽  
Significant Clinical Improvement ◽  
Tnfα Inhibitor ◽  
Factor Α

BackgroundImmune checkpoint inhibitors (ICIs) have significantly improved outcomes for patients with numerous cancers. However, these therapies are associated with immune-related adverse events (irAEs), which are inflammatory side effects potentially affecting any organ. Cases of ICI-induced inflammatory arthritis have also been reported. In general, mild irAEs are treated with corticosteroids, while tumour necrosis factor-α (TNFα) inhibitors are reserved for refractory cases. However, prolonged use of TNFα inhibitor (TNFαi) can induce widespread, significant immunosuppression, which can negatively impact the antitumour efficacy of ICI therapy. Therefore, in clinical scenarios where patients develop severe immunotherapy-induced irAEs, an unmet need exists for alternative therapeutic strategies that are effective and without immune dampening effects.Case reportsThe anti-interleukin (IL)−6 receptor antibody, tocilizumab, is a biological agent Food and Drug Administration approved for the treatment of rheumatoid arthritis and juvenile idiopathic arthritis. Here, we report on three patients who developed severe polyarthritis while receiving ICI therapy and were treated with tocilizumab. All three patients demonstrated significant clinical improvement; one patient maintained a durable antitumour response derived from checkpoint inhibition.ConclusionsThese three cases suggest that anti-IL-6 receptor antibody may be an effective alternative to corticosteroids or TNFαi for the treatment of arthritis irAEs.

scholarly journals Efficacy of nicotine administration on obsessions and compulsions in OCD: a systematic review

2020 ◽  
Vol 19 (1) ◽  
Author(s):  
Daria Piacentino ◽  
Annalisa Maraone ◽  
Valentina Roselli ◽  
Isabella Berardelli ◽  
Massimo Biondi ◽  
...  
Keyword(s):  
Systematic Review ◽  
Ethical Issues ◽  
Case Reports ◽  
Treatment Strategies ◽  
Case Series ◽  
Symptom Improvement ◽  
Open Label ◽  
Cross Sectional ◽  
Positive Effects ◽  
Nicotine Administration

Abstract Background Preliminary studies have tested nicotine as a novel treatment for OCD patients who respond partially/incompletely or not at all to first and second-line treatment strategies, with the former represented by SSRIs or clomipramine, and the latter by switching to another SSRI, or augmentation with atypical antipsychotics, and/or combination with/switching to cognitive–behavioural therapy. Some studies found nicotine-induced reduction of obsessive thoughts and/or compulsive behaviour in OCD patients. We aimed to evaluate the efficacy of nicotine administration in OCD patients. Methods We searched the PubMed, ScienceDirect Scopus, CINHAL, Cochrane, PsycINFO/PsycARTICLES, and EMBASE databases from inception to the present for relevant papers. The ‘Preferred Reporting Items for Systematic Review and Meta-Analyses’ (PRISMA) standards were used. We included all studies focusing on the effects of nicotine administration on OCD patients’ obsessions or compulsions. Studies could be open-label, cross-sectional, randomized controlled trials, case series or case reports. Results A total of five studies could be included. Nicotine administration may ameliorate behavioural features and recurrent thoughts of severe, treatment-resistant OCD patients; however, in one study it was not associated with OC symptom improvement or cognitive enhancement across various executive function subdomains. Conclusions Although encouraging, the initial positive response from the use of nicotine in OCD needs testing in large controlled studies. This, however, raises ethical issues related to nicotine administration, due to its addiction potential, which were not addressed in the limited literature we examined. As an alternative, novel treatments with drugs able to mimic only the positive effects of nicotine could be implemented.

scholarly journals P416 Results of the first paediatric randomised controlled trial of faecal microbiota transplant for ulcerative colitis

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S379-S380
Author(s):  
N Pai ◽  
J Popov ◽  
L Hill ◽  
E Hartung ◽  
K Grzywacz ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Clinical Response ◽  
Healthy Donor ◽  
Activity Index ◽  
Case Reports ◽  
Case Series ◽  
Faecal Microbiota ◽  
Open Label ◽  
Randomised Controlled

Abstract Background The role of faecal microbiota transplant (FMT) for the treatment of ulcerative colitis (UC) has been reported across 4 randomised-controlled trials (RCT) in adults. Promising data have emerged from small, open-label paediatric case series and case reports but a proper blinded, placebo-controlled RCT has not been described in children. We report results from the first multicentre RCT of FMT in paediatric UC patients, conducted over 36 months in Ontario and Quebec, Canada. Methods We enrolled 25 children, ages 4–17 years old with active UC across two tertiary IBD clinics. Patients had active inflammation and remained on stable doses of medication at entry. Blinded participants received enemas containing healthy donor stool (active) or normal saline (placebo), 2×/week for 6 weeks. Faecal calprotectin (fCal), C-reactive protein (CRP), and paediatric ulcerative colitis activity index (PUCAI) scores were compared between groups during intervention, and at four follow-up time points over 30 weeks. Donor and recipient stools were measured for 16s rRNA and metagenomics analyses. Results In intention-to-treat (ITT) analysis, FMT (n = 13) at 6 weeks was more likely to improve clinical response (OR 9.3, 95% CI [0.7, 122.6]), CRP (OR 4.7, 95% CI [0.8, 28.4]), and fCal (OR 13.3, 95% CI [1.1, 166.4]) from baseline compared with placebo (n = 12). FMT at 30 weeks was also more likely than placebo to improve clinical response, CRP, and fCal (Table 1). In ITT analysis of the open-label arm (n = 7), FMT at 6 weeks and 30 weeks decreased CRP (−42.9%, −28.6%), fCal (−28.6%, −42.9%), and PUCAI score (−14.3%, −42.9%) from baseline. Conclusion Serial FMT enemas containing healthy donor microbiota led to greater improvements in serum and stool inflammatory markers, and rates of clinical response, in paediatric patients with active UC compared with placebo. These improvements largely persisted beyond 6 months after final FMT treatment. This study offers the strongest preliminary evidence, from a blinded, placebo-controlled multicentre RCT for the role of FMT in the management of paediatric UC.

Steroid-resistant sarcoidosis: is antagonism of TNF-α the answer?

2007 ◽  
Vol 112 (5) ◽  
pp. 281-289 ◽  
Author(s):  
Bart G. Denys ◽  
Yves Bogaerts ◽  
Kenneth L. Coenegrachts ◽  
An S. De Vriese
Keyword(s):  
Case Reports ◽  
Controlled Trial ◽  
Critical Role ◽  
Case Series ◽  
Experimental Treatment ◽  
Diagnostic Challenge ◽  
Open Label ◽  
Modest Improvement ◽  
Steroid Resistant ◽  
Tnf Α

Steroid-resistant sarcoidosis has conventionally been treated with various drugs, including methotrexate, azathioprine, cyclophosphamide, cyclosporine, antimalarial drugs and thalidomide, with variable success. There is a compelling need for more efficient and safer alternatives to these agents. Several lines of evidence suggest a critical role of TNF-α (tumour necrosis factor-α) in the initiation and organization of sarcoid granulomas. Inhibition of TNF-α with monoclonal antibodies has therefore received attention as a potential treatment option in therapy-resistant sarcoidosis. A number of case reports and small case series describe successful treatment of refractory disease with infliximab. Preliminary evidence from an RCT (randomized controlled trial) with infliximab in pulmonary sarcoidosis suggests a modest improvement in functional and radiological parameters. In contrast, the results with etanercept have been disappointing, perhaps related to differences in the mechanism of TNF-α blockade. The experience with adalimumab in sarcoidosis is too limited to draw conclusions. An open-label study and an RCT evaluating the efficacy of adalimumab in sarcoidosis with pulmonary and cutaneous involvement respectively, have been initiated. Although TNF-α antagonists appear relatively safe, especially when compared with conventional agents, caution is warranted in view of the increased incidence of tuberculosis, which may be a particular diagnostic challenge in patients with sarcoidosis. Pending publication of the RCTs, the use of TNF-α blockade in sarcoidosis should remain in the realm of experimental treatment.

scholarly journals Apremilast as an Off-Label Therapeutic Agent

2021 ◽  
Vol 5 (3) ◽  
pp. 203-227
Author(s):  
Justin Marson ◽  
Mark Lebwohl
Keyword(s):  
Atopic Dermatitis ◽  
Psoriatic Arthritis ◽  
Combination Therapy ◽  
Hidradenitis Suppurativa ◽  
Case Reports ◽  
Case Series ◽  
Open Label ◽  
Off Label ◽  
Inflammatory Dermatoses ◽  
Randomized Control

Objective: To review the literature regarding the efficacy and safety of off-label use of apremilast in combination therapies for psoriasis and psoriatic arthritis and for other currently off-label inflammatory dermatoses. Methods: The Medline database was queried for all relevant articles published between 2014 and 2021 using exploded MeSH terms and keywords pertaining to the following themes: off-label, combination therapy, biologics, biologic therapy, methotrexate, and systemic psoriasis therapy. The Boolean term “AND” was used to find the intersection of these themes with the term “apremilast.” Results: 8 case series and 6 case reports investigated the use of apremilast in combination therapy for psoriasis and psoriatic arthritis. Addition of apremilast improved PASI scores by 31.8-77.4% among case series and 80-100% among case reports with adverse effects primarily consisting of gastrointestinal symptoms. 5 randomized-control trials (RCT), 9 open-label trials, 18 case series, and 30 case reports investigated the use of apremilast for off-label dermatoses. In RCTs, apremilast showed potential efficacy for atopic dermatitis and hidradenitis suppurativa. Open-label trials found apremilast efficacious for atopic dermatitis, allergic contact dermatitis, chronic pruritus, cutaneous sarcoidosis, discoid lupus erythematosus, hidradenitis suppurativa, lichen planus, prurigo nodularis, rosacea, and vitiligo. Limitations: Small sample size and short follow duration up for available randomized-control and open-label trials. Current data from case series/reports potentially limits generalizability of findings. Conclusion: Apremilast's safety profile makes it a potential efficacious, non-biologic systemic agent for monotherapy and combination therapy for a wide range of inflammatory dermatoses.

scholarly journals Activation of Interferon-Stimulated Transcriptomes and ACE2 Isoforms in Human Airway Epithelium Is Curbed by Janus Kinase Inhibitors

2020 ◽  
Author(s):  
Hye Kyung Lee ◽  
Olive Jung ◽  
Lothar Hennighausen
Keyword(s):  
Airway Epithelium ◽  
Kinase Inhibitors ◽  
Regulatory Elements ◽  
Janus Kinase ◽  
Cell Tropism ◽  
Jak Inhibitors ◽  
Janus Kinase Inhibitors ◽  
Angiotensin Converting Enzyme 2 ◽  
Human Airway ◽  
Human Airway Epithelium

Abstract SARS-CoV-2 infection of human airway epithelium activates genetic programs that lead to progressive hyperinflammation in COVID-19 patients. Here we report on genetic programs activated by interferons and the suppression by Janus kinase (JAK) inhibitors. The angiotensin-converting enzyme 2 (ACE2) is the receptor for SARS-CoV-2 and deciphering its regulation is paramount for understanding the cell tropism of SARS-CoV-2 infection. We identified candidate regulatory elements in the ACE2 locus in human primary airway cells and lung tissue. Activating histone and promoter marks and Pol II loading characterize the intronic dACE2 and define novel candidate enhancers distal to the genuine ACE2 promoter and within additional introns. dACE2, and to a lesser extent ACE2, RNA levels increased in primary cells treated with interferons and this induction was mitigated by JAK inhibitors that are used therapeutically in COVID-19 patients. Our analyses provide insight into ACE2 regulatory elements and highlight JAK inhibitors as suitable tools to suppress interferon-activated genetic programs in bronchial cells.

scholarly journals Monitoring the transition of patients on biologics in rheumatoid arthritis: Consensus guidance for pharmacists

2021 ◽  
Vol 19 (3) ◽  
pp. 2377
Author(s):  
Denis Choquette ◽  
Jonathan Chan ◽  
Mohammad Bardi ◽  
Carolyn Whiskin ◽  
Gabriel Torani ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Best Practices ◽  
Kinase Inhibitors ◽  
Unmet Need ◽  
Nominal Group Technique ◽  
Janus Kinase ◽  
Nominal Group ◽  
Nocebo Effect ◽  
Patient Journey ◽  
Janus Kinase Inhibitors

Background: Recent approvals for novel agents such as the small molecule Janus kinase inhibitors (JAKi), combined with the advent of biosimilars has widened the gamut of available therapeutic options in the treatment of rheumatoid arthritis (RA). This combined with the introduction of mandatory non- medical switches to biosimilars in some jurisdictions by both public and private payors has led to a significant increase in the volume of therapeutic changes for patients. Pharmacists are well positioned to ensure effective and safe transitions, however there is a significant unmet need for objective and subjective clinical guidance around therapy as well disease state monitoring in RA that facilitates best practices throughout the patient journey. Objective: In this paper we aim to create a consensus derived monitoring algorithm for pharmacists to facilitate best practices throughout therapeutic transitions from originator biologic to other originator biologics, biosimilars, and Janus kinase inhibitors in RA. Methods: The Nominal Group Technique (NGT) was used to understand if consensus could be found among the participants. Clinically relevant questions were developed to capture solutions to the identified unmet need. The faculty considered the questions as individuals, and privately generated answers/ideas. After discussion and consideration, the participants ranked the ideas and established a consensus. Results: Based on the outcome of the consensus discussions, an algorithm was created to help guide pharmacists through therapeutic transitions in RA. The tool covers important topics such as pre-transition considerations, avoiding the nocebo effect for biosimilars, specific considerations for each drug or class, monitoring efficacy, and when to refer. Conclusions: New classes of anti-rheumatic drugs including JAKi, along with the introduction of biosimilars are presenting more opportunity for therapeutic changes and monitoring in patients with RA. We hope our evidence-based consensus derived guidance tool will assist frontline pharmacists in supporting their patients to a successful therapeutic transition in RA.

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