The Experts below are selected from a list of 987 Experts worldwide ranked by ideXlab platform
Emma D. Deeks - One of the best experts on this subject based on the ideXlab platform.
-
Sarecycline: First Global Approval
2019Co-Authors: Emma D. DeeksAbstract:Compliance with Ethical StandardsDisclosure: The preparation of this review was not supported by any external funding.Conflicts of interest: Emma Deeks is a Salaried Employee of Adis/Springer, is responsible for the article content and declares no relevant conflicts of interest.Additional information about this Adis Drug Review can be found hereAbstractSarecycline (Seysara™) is an oral, once-daily, tetracycline-class drug for which a tablet formulation is approved in the USA for the treatment of inflammatory lesions of non-nodular moderate to severe acne vulgaris in patients aged ≥ 9 years. The drug was developed by Paratek and Allergen and later acquired by Almirall S.A. (a Barcelona-based pharmaceutical company focused on medical dermatology). Sarceycline tablets were approved in early October 2018 and are planned to be available for patients in January 2019. Sarecycline capsules have also been studied in the USA, but no recent reports of development have been identified for this formulation. There are currently no clinical trials underway assessing sarecycline in rosacea. This article summarizes the milestones in the development of sarecycline leading to this first approval for the treatment of inflammatory lesions of non-nodular moderate to severe acne vulgaris.© Springer Nature Switzerland AG 2019
-
GP2015: An Etanercept Biosimilar
2018Co-Authors: Emma D. DeeksAbstract:Compliance with Ethical Standards Disclosure: The preparation of this review was not supported by any external funding. Emma Deeks is a Salaried Employee of Adis/Springer, is responsible for the article content and declares no relevant conflicts of interest. Additional information about this Adis Drug Review can be found here. Abstract GP2015 is the second biosimilar of the reference p75 TNF receptor-Fc fusion protein etanercept. It is approved for use in all indications for which reference etanercept is approved, including rheumatoid arthritis, juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, non-radiographic axial spondyloarthritis, plaque psoriasis and paediatric plaque psoriasis. GP2015 has similar physiochemical and pharmacodynamic properties to those of reference etanercept, and the pharmacokinetic biosimilarity of the agents has been shown in healthy volunteers. GP2015 demonstrated clinical efficacy equivalent to that of reference etanercept in patients with moderate-to-severe plaque psoriasis; the tolerability, safety and immunogenicity profiles of the two agents were also generally similar. Switching between GP2015 and reference etanercept had no impact on clinical efficacy, tolerability or immunogenicity. The role of reference etanercept in the management of inflammatory autoimmune conditions is well established and GP2015 provides an effective biosimilar alternative for patients requiring etanercept therapy. Access to the full article can be found here. © Springer International Publishing AG, part of Springer Nature 2017
-
Fulvestrant: A Review in the First-Line Treatment of Advanced Breast Cancer
2018Co-Authors: Emma D. DeeksAbstract:Compliance with Ethical StandardsFunding: The preparation of this review was not supported by any external funding.Conflicts of interest: Emma Deeks is a Salaried Employee of Adis/Springer, is responsible for the article content and declares no relevant conflicts of interest.Additional information about this Adis Drug Review can be found here.AbstractFulvestrant (Faslodex®), a selective estrogen receptor (ER) down-regulator, is now indicated for the treatment of ER positive/human epidermal growth factor receptor 2 negative advanced breast cancer in postmenopausal women previously untreated with endocrine therapy. In the phase 3 FALCON trial conducted in this setting, intramuscular fulvestrant 500 mg/month (plus an additional dose at 2 weeks) was significantly more effective in prolonging progression-free survival (PFS) than oral anastrozole 1 mg/day (particularly in patients with non-visceral disease), with this benefit seemingly driven by fulvestrant recipients responding significantly longer to treatment. Other efficacy measures, including objective response rate, did not significantly or markedly differ between the two regimens and median overall survival was not yet calculable. Fulvestrant was generally well tolerated in this trial, displaying an overall tolerability profile consistent with its known tolerability in other breast cancer settings. Thus, monotherapy with intramuscular fulvestrant is a generally well tolerated and more effective treatment option than standard-of-care anastrozole for advanced breast cancer in postmenopausal women not previously treated with endocrine therapy. Access to the full article can be found here.© Springer International Publishing AG, part of Springer Nature 2017
-
Neratinib: First Global Approval
2018Co-Authors: Emma D. DeeksAbstract:Compliance with Ethical StandardsFunding: The preparation of this review was not supported by any external funding.Conflicts of interest: During the peer review process the manufacturer of the agent under review was offered an opportunity to comment on the article. Changes resulting from any comments received were made by the author on the basis of scientific completeness and accuracy. Emma Deeks is a Salaried Employee of Adis/Springer, is responsible for the article content and declares no relevant conflicts of interest.Additional information about this Adis Drug Review can be found here.AbstractNeratinib (Nerlynx™) is an oral, irreversible inhibitor of the human epidermal growth factor receptors HER1 (EGFR), HER2 and HER4. The drug originally arose from research by Wyeth (now Pfizer) and is now being developed by Puma Biotechnology primarily for the treatment of HER2-positive (HER+) breast cancer. Neratinib is approved in the USA for the extended adjuvant treatment of patients with HER2+ early-stage breast cancer who have been previously treated with a trastuzumab-based regimen, and is in the preregistration phase for this indication in the EU. Neratinib, as monotherapy and/or combination therapy, is also in phase 3 development for metastatic breast cancer and in phase 1/2 development for advanced breast cancer and other solid tumours, including non-small cell lung cancer, colorectal cancer and glioblastoma. This article summarizes the milestones in the development of neratinib leading to this first approval for breast cancer. Access to the full article can be found here.© Springer International Publishing AG, part of Springer Nature 2017
-
Raltegravir Once Daily: A Review in HIV-1 Infection
2018Co-Authors: Emma D. DeeksAbstract:Compliance with Ethical StandardsFunding: The preparation of this review was not supported by any external funding.Conflicts of interest: Emma Deeks is a Salaried Employee of Adis/Springer, is responsible for the article content and declares no relevant conflicts of interest.Additional information about this Adis Drug Review can be found here.AbstractA once-daily tablet formulation (Isentress® HD; Isentress® 600 mg) of the integrase strand transfer inhibitor raltegravir is now available for the treatment of HIV-1 infection. The 600 mg tablet has improved bioavailability versus the existing twice-daily 400 mg tablet (due, at least in part, to differences in tablet dissolution) and the recommended dosage is 1200 mg (i.e. two 600 mg tablets) once daily. In combination with emtricitabine/tenofovir disoproxil fumarate in treatment-naïve adults, once-daily raltegravir 1200 mg provided virological suppression non-inferior to that seen with twice-daily raltegravir 400 mg over 48 and 96 weeks in the phase 3 ONCEMRK trial. The once-daily raltegravir regimen was also generally well tolerated in this study, displaying a tolerability profile similar to that of the twice-daily regimen. The once-daily tablet simplifies and improves the convenience of raltegravir regimens, although its impact on adherence has yet to be determined. Thus, once-daily raltegravir tablets are a convenient alternative to twice-daily raltegravir tablets for the treatment of HIV-1, further expanding the therapeutic options available to meet the diverse needs of this patient population. Access to the full article can be found here.© Springer International Publishing AG, part of Springer Nature 2017
Shellenberger, Dillon T - One of the best experts on this subject based on the ideXlab platform.
-
Implications and Effectiveness of Half-time Pay for Salaried Employee Overtime
University of Wyoming. Libraries, 2018Co-Authors: Shellenberger, Dillon TAbstract:Half-time pay is an option for Salaried Employees to receive as an overtime benefit. Based on a fluctuating workweek schedule, Employees with varying hours can be compensated for additional hours worked over 40, through the use of half-time pay. If an Employee works less than 40 hours in a week, he/she will still receive the full salary compensation; however, any hours over 40 will receive a wage at half-time of normal pay. My research included examining current policies and analyzing the potentially positive and negative effects of half-time pay for Salaried Employee overtime. Factors such as retention, fairness, and equity were considered when evaluating the potential effectiveness of half-time pay. By considering different management techniques for motivating Employees in the workplace and considering the pros and cons of using half-time pay as an overtime pay method, I make a recommendation of how and when half-time pay should be used. Executed in the right conditions, using half-time pay for a Salaried Employee's overtime can be an effective tool for increasing both Employee motivation and morale
-
Implications and Effectiveness of Half-time Pay for Salaried Employee Overtime
Wyoming Scholars Repository, 2017Co-Authors: Shellenberger, Dillon TAbstract:Half-time pay is an option for Salaried Employees to receive as an overtime benefit. Based on a fluctuating workweek schedule, Employees with varying hours can be compensated for additional hours worked over 40, through the use of half-time pay. If an Employee works less than 40 hours in a week, he/she will still receive the full salary compensation; however, any hours over 40 will receive a wage at half-time of normal pay. My research included examining current policies and analyzing the potentially positive and negative effects of half-time pay for Salaried Employee overtime. Factors such as retention, fairness, and equity were considered when evaluating the potential effectiveness of half-time pay. By considering different management techniques for motivating Employees in the workplace and considering the pros and cons of using half-time pay as an overtime pay method, I make a recommendation of how and when half-time pay should be used. Executed in the right conditions, using half-time pay for a Salaried Employee’s overtime can be an effective tool for increasing both Employee motivation and morale. Keywords: half-time, Salaried Employee, overtime, fluctuating workwee
Hervé Gosselin - One of the best experts on this subject based on the ideXlab platform.
-
Peut-on considerer qu’un nouveau droit du maintien dans l’emploi est en cours d’élaboration ?
'OpenEdition', 2010Co-Authors: Hervé GosselinAbstract:The employer’s obligations regarding the reclassification of a Salaried Employee who cannot remain at his job, is subject to two different legal rules, depending on whether the Employee is declared “able,” subject to adaptation of his workstation, or "disabled" by the occupational physician. This distinction is not relevant ; it is a source of legal insecurity and it orients the judge’s control towards the regularity of the contestation of work disability at the expense of a verification that the employer has done everything necessary to adapt the position or to reclassify the Salaried Employee. However, the growing use of the concept of "result safety obligation" by the Chambre sociale de la Cour de cassation, and the influence of the community antidiscrimination law could be at the origin of a reorientation of this control towards the employer’s obligation to comply with reclassification. In this field, the use of the Employees’ competences by the representative institutions could only encourage the judge to exert this delicate control, which must reconcile the employers’ respect for their very strong obligations and their necessary consideration of management constraints
-
Peut-on considerer qu’un nouveau droit du maintien dans l’emploi est en cours d’élaboration ? Is a new right to maintain one’s employment being developed? ¿Podemos considerar que permanecer en el empleo es un nuevo derecho en vías de ser elaborado ?
Institut de Recherche Robert-Sauvé en Santé et en Sécurité du Travail (IRSST), 2010Co-Authors: Hervé GosselinAbstract:Les obligations qui pèsent sur l’employeur en matière de reclassement d’un salarié qui ne peut plus se maintenir à son poste de travail relèvent de deux régimes juridiques différents, selon que le salarié est déclaré apte sous réserve d’adaptations du poste, ou inapte, par le médecin du travail. Cette distinction n’est pas pertinente, elle est source d’insécurité juridique, et elle oriente trop le contrôle du juge vers la régularité de la contestation de l’inaptitude au détriment d’une vérification que l’employeur a réellement fait tous les efforts nécessaires pour adapter le poste de travail ou reclasser le salarié. Cependant, l’utilisation croissante par la Chambre sociale de la Cour de cassation de la notion d’obligation de sécurité de résultat et l’influence du droit communautaire anti-discrimination pourraient être à l’origine d’une réorientation de ce contrôle vers le respect de l’obligation de reclassement par l’employeur. L’utilisation par les institutions représentatives du personnel de leurs compétences dans ce domaine ne pourrait que favoriser l’exercice par le juge de ce contrôle délicat, qui doit concilier le respect d’une très forte obligation de l’employeur et la prise en compte des contraintes de gestion qui s’imposent à lui.The employer’s obligations regarding the reclassification of a Salaried Employee who cannot remain at his job, is subject to two different legal rules, depending on whether the Employee is declared “able,” subject to adaptation of his workstation, or "disabled" by the occupational physician. This distinction is not relevant ; it is a source of legal insecurity and it orients the judge’s control towards the regularity of the contestation of work disability at the expense of a verification that the employer has done everything necessary to adapt the position or to reclassify the Salaried Employee. However, the growing use of the concept of "result safety obligation" by the Chambre sociale de la Cour de cassation, and the influence of the community antidiscrimination law could be at the origin of a reorientation of this control towards the employer’s obligation to comply with reclassification. In this field, the use of the Employees’ competences by the representative institutions could only encourage the judge to exert this delicate control, which must reconcile the employers’ respect for their very strong obligations and their necessary consideration of management constraints.Las obligaciones que pesan sobre el empleador en materia de reclasificación de un asalariado que ya no puede mantenerse en su puesto de trabajo, se refieren a dos regímenes jurídicos diferentes, dependiendo de si el asalariado es declarado apto, bajo la reserva de las adaptaciones del puesto, o incapacitado por el médico del trabajo. Esa distinción no es pertinente, ya que es fuente de inseguridad jurídica y orienta demasiado el control del juez hacia la regularidad de la impugnación de la incapacidad, en detrimento de la verificación de los esfuerzos necesarios para adaptar el puesto de trabajo o reclasificar al asalariado. Sin embargo, la utilización creciente, por la cámara social del Tribunal supremo, de la noción de “obligación de seguridad del resultado” y la influencia del derecho comunitario anti-discriminación, podrían ser el origen de una reorientación de este control hacia el respeto de la obligación a reclasificar por parte del empleador. La utilización de sus competencias en este campo, por parte de las instituciones representativas del personal, podrían favorecer el ejercicio de este control delicado, por el juez, quien debe conciliar el respeto de una gran obligación del empleador y las inconveniencias administrativas que se le imponen
Hannah A. Blair - One of the best experts on this subject based on the ideXlab platform.
-
Brodalumab: A Review in Moderate to Severe Plaque Psoriasis
2018Co-Authors: Hannah A. BlairAbstract:Compliance with Ethical StandardsFunding: The preparation of this review was not supported by any external funding.Conflicts of interest: Hannah Blair is a Salaried Employee of Adis/Springer, is responsible for the article content and declares no relevant conflicts of interest.Additional information about this Adis Drug Review can be found here.AbstractBrodalumab (Kyntheum) is a human antiinterleukin-17 receptor A (IL-17RA) monoclonal antibody available for use in patients with moderate to severe plaque psoriasis. In the phase III AMAGINE trials in this patient population, 12 weeks of induction therapy with subcutaneous brodalumab was superior to placebo in terms of the proportion of patients with ≥ 75% improvement in the Psoriasis Area and Severity Index score (PASI 75) and the proportion of patients with a static Physician Global Assessment score of 0 or 1. Brodalumab was also superior to ustekinumab for PASI 100 (i.e. complete skin clearance) at week 12. Health-related quality of life (HR-QOL) outcomes improved to a significantly greater extent with brodalumab than with placebo. Moreover, brodalumab was more effective than placebo in patients with difficult-totreat nail or scalp psoriasis. Brodalumab was generally well tolerated, with low rates of immunogenicity. Efficacy was sustained and brodalumab remained well tolerated during up to 52 weeks of maintenance therapy. Thus, subcutaneous brodalumab is a useful addition to the treatment options currently available for patients with moderate to severe plaque psoriasis. Access to the full article can be found here.© Springer International Publishing AG, part of Springer Nature 2018
-
Pemafibrate: First Global Approval
2018Co-Authors: Hannah A. BlairAbstract:Disclosure: The preparation of this review was not supported by any external funding. During the peer review process the manufacturer of the agent under review was offered an opportunity to comment on the article. Changes resulting from any comments received were made by the author on the basis of scientific completeness and accuracy. H. A. Blair is a Salaried Employee of Adis, Springer SBM. Additional information about this Adis Drug Review can be found here.AbstractPemafibrate (Parmodia®) is a novel, highly selective peroxisome proliferator-activated receptor (PPAR)-α modulator (SPPARM). It acts by binding to PPAR-α and regulating the expression of target genes that modulate lipid metabolism, thereby decreasing plasma triglyceride levels and increasing high-density lipoprotein cholesterol levels. Developed by Kowa Company, Ltd., oral pemafibrate has been approved in Japan for the treatment of hyperlipidaemia (including familial hyperlipidaemia). This article summarizes the milestones in the development of pemafibrate leading to this first global approval for hyperlipidaemia. Access to the full article can be found here.© Springer International Publishing AG, part of Springer Nature 2017
-
Daratumumab: A Review in Relapsed or Refractory Multiple Myeloma
2018Co-Authors: Hannah A. BlairAbstract:Compliance with Ethical StandardsFunding: The preparation of this review was not supported by any external funding.Conflicts of interest: Hannah Blair is a Salaried Employee of Adis/Springer, is responsible for the article content and declares no relevant conflicts of interest.Additional information about this Adis Drug Review can be found here.AbstractIntravenous daratumumab (DARZALEX®) is a first-in-class human IgG1κ monoclonal antibody against CD38 available for use in patients with relapsed and/or refractory multiple myeloma. In phase I/II and II trials and a pooled analysis of these studies, daratumumab monotherapy induced an overall response (partial response or better) in approximately one-third of patients; responses were rapid, deep and durable. An overall survival (OS) benefit was seen with daratumumab monotherapy, including in patients with a minimal response or stable disease. In phase III trials, daratumumab in combination with either bortezomib plus dexamethasone or lenalidomide plus dexamethasone significantly prolonged progression-free survival and induced deep and durable responses compared with bortezomib plus dexamethasone or lenalidomide plus dexamethasone. An OS benefit with daratumumab triple combination therapy is yet to be demonstrated (as the OS data were not mature at the time of the last analysis). Daratumumab was generally well tolerated when used as monotherapy and had a generally manageable tolerability profile when used in combination therapy. Infusion-related reactions (IRRs) were the most common adverse events; these were predominantly grade 1 or 2 and mostly occurred during the first infusion. The most common grade 3–4 adverse events associated with daratumumab triple combination therapy were thrombocytopenia, neutropenia and anaemia. Although final OS data are awaited, current evidence indicates that daratumumab is a valuable addition to the treatment options currently available for patients with relapsed or refractory multiple myeloma. Access to the full article can be found here.© Springer International Publishing AG, part of Springer Nature 2017
-
Dimethyl Fumarate: A Review in Plaque Psoriasis
2018Co-Authors: Hannah A. BlairAbstract:Compliance with Ethical StandardsFunding: The preparation of this review was not supported by any external funding.Conflicts of interest: Hannah Blair is a Salaried Employee of Adis/Springer, is responsible for the article content and declares no relevant conflicts of interest.Additional information about this Adis Drug Review can be found here.AbstractFumaric acid esters (FAEs) have been used in the treatment of psoriasis in some European countries for over 20 years, and are recommended in the European guidelines for the management of moderate to severe plaque psoriasis. Dimethyl fumarate (Skilarence®; hereafter referred to as DMF) is an orally administered FAE indicated for the treatment of moderate to severe plaque psoriasis in adults in need of systemic medicinal therapy; unlike other available FAEs, it is not formulated in combination with monoethyl fumarate salts. EU approval was based on results of the phase III BRIDGE trial, and supported by previous publications of FAE preparations, including a combination of FAEs containing dimethyl fumarate and monoethyl fumarate salts (DMF/MEF; Fumaderm®). In the BRIDGE trial, DMF was superior to placebo in terms of the proportion of patients achieving a ≥ 75% improvement from baseline in the Psoriasis Area and Severity Index (PASI 75) and a Physician Global Assessment score of 0 (clear) or 1 (almost clear) at week 16. DMF was also noninferior to DMF/MEF for PASI 75 at week 16. Patients receiving DMF also reported clinically meaningful improvements in body surface area involvement and health-related quality of life. The safety profile of DMF was similar to that of DMF/MEF, and no major or unexpected safety concerns were identified. The most common adverse events (flushing and gastrointestinal disorders) occurred mainly during the first few weeks of treatment. Currently available data indicate that DMF is an effective oral systemic treatment option for patients with moderate to severe plaque psoriasis. Access to the full article can be found here.© Springer International Publishing AG, part of Springer Nature 2017
Sohita Dhillon - One of the best experts on this subject based on the ideXlab platform.
-
Neratinib in Early-Stage Breast Cancer: A Profile of Its Use in the EU
2018Co-Authors: Sohita DhillonAbstract:Compliance with Ethical StandardsFunding The preparation of this review was not supported by any external funding.Disclosure The preparation of this review was not supported by any external funding. Sohita Dhillon is a Salaried Employee of Adis/Springer, is responsible for the article content and declares no relevant conflicts of interest.Additional information about this Adis Drug Review can be found here. Abstract Neratinib (Nerlynx®) is an oral, irreversible tyrosine kinase inhibitor of human epidermal growth factor receptor 1 (HER1), HER2 and HER4. Neratinib therapy for 12 months significantly reduced the risk of invasive disease recurrence or death relative to placebo at both 2 and 5 years post-randomization in the pivotal ExteNET trial in women with early-stage HER2-positive breast cancer who had completed adjuvant trastuzumab. Subgroup analyses showed that patients with hormone receptor (HRc)-positive disease derived greater benefit with neratinib than patient with HRc-negative disease, and patients who initiated neratinib within 1 year of completing trastuzumab had better outcomes than those who started treatment 1–2 years after trastuzumab. This led to the approval of neratinib in the EU as extended adjuvant therapy for patients with early-stage hormone receptor (HRc)-positive, HER2-positive breast cancer and who are
-
Meningococcal Quadrivalent Tetanus Toxoid Conjugate Vaccine (MenACWY-TT; Nimenrix®): A Review
2018Co-Authors: Sohita DhillonAbstract:Compliance with Ethical StandardsFunding: The preparation of this review was not supported by any external funding. Conflicts of interest: Sohita Dhillon is a Salaried Employee of Adis/Springer, is responsible for the article content and declares no relevant conflicts of interest.Additional information about this Adis Drug Review can be found here.AbstractMenACWY-TT (Nimenrix®) is a quadrivalent meningococcal tetanus toxoid conjugate vaccine licensed in Europe for active immunisation of individuals aged ≥6 weeks against invasive disease caused by Neisseria meningitidis capsular groups A, C, W and Y. MenACWY-TT is the first quadrivalent conjugate vaccine to be approved in Europe for use in infants as young as 6 weeks of age. Numerous phase II–IIIb clinical studies showed that intramuscular MenACWY-TT administered as primary or booster vaccination was highly immunogenic for all four vaccine capsular groups and had an acceptable reactogenicity profile in individuals aged 6 weeks to ≥56 years. MenACWY-TT is as immunogenic and safe as other previously licensed monovalent capsular group C or quadrivalent capsular groups A, C, W and Y meningococcal vaccines and can be coadministered with other routine vaccines without adversely affecting the immunogenicity or safety profiles of either vaccine. Current data indicate that primary and booster vaccination with MenACWY-TT is a valuable and safe option for broadening meningococcal protection against four capsular groups across a broad age range, starting as early as 6 weeks of age. Access to the full article can be found here.© Springer International Publishing AG, part of Springer Nature 2017
-
Semaglutide: First Global Approval
2018Co-Authors: Sohita DhillonAbstract:Compliance with Ethical StandardsFunding: The preparation of this review was not supported by any external funding.Conflicts of interest: During the peer review process the manufacturer of the agent under review was offered an opportunity to comment on the article. Changes resulting from any comments received were made by the authors on the basis of scientific completeness and accuracy. Sohita Dhillon is a Salaried Employee of Adis/Springer, is responsible for the article content and declares no relevant conflicts of interestAdditional information about this Adis Drug Review can be found here.AbstractNovo Nordisk has developed a subcutaneous formulation of semaglutide (Ozempic®), a modified human glucagon-like peptide-1 (GLP-1) analogue, for the treatment of type 2 diabetes mellitus. It has been developed using Novo Nordisk's proprietary protein-acylation technology, and is administered using an injection device. Semaglutide lowers blood glucose by stimulating the release of insulin and also lowers body weight. Once-weekly subcutaneous semaglutide has recently been approved in the US, Puerto Rico and Canada, and has received a positive opinion in the EU for the treatment of patients with type 2 diabetes. It will be launched as the Ozempic® Pen, a pre-filled device. Semaglutide is also under regulatory review in Japan and Switzerland for the treatment of type 2 diabetes. Clinical development for obesity, non-alcoholic steatohepatitis and non-alcoholic fatty liver disease is underway worldwide. This article summarizes the milestones in the development of semaglutide leading to this first approval for type 2 diabetes. Access to the full article can be found here.© Springer International Publishing AG, part of Springer Nature 2018
-
Tofacitinib: A Review in Rheumatoid Arthritis
2018Co-Authors: Sohita DhillonAbstract:Compliance with Ethical StandardsFunding: The preparation of this review was not supported by any external funding.Conflicts of interest: Sohita Dhillon is a Salaried Employee of Adis/Springer, is responsible for the article content and declares no relevant conflicts of interest.Additional information about this Adis Drug Review can be found here.AbstractTofacitinib (Xeljanz®) is a potent, selective JAK inhibitor that preferentially inhibits Janus kinase (JAK) 1 and JAK3. In the EU, oral tofacitinib 5 mg twice daily is indicated for the treatment of moderate to severe active rheumatoid arthritis (RA) in adult patients who have responded inadequately to, or who are intolerant of, one or more DMARDs. Several clinical studies of ≤24 months’ duration showed that tofacitinib monotherapy (as first- or second-line treatment) and combination therapy with a conventional synthetic DMARD (as second- or third-line treatment) was effective in reducing signs and symptoms of disease and improving health-related quality of life (HR-QOL), with benefits sustained during long-term therapy (≤96 months). Tofacitinib monotherapy inhibited progression of structural damage in methotrexate-naïve patients during ≤24 months’ treatment, with beneficial effects also seen in patients receiving tofacitinib plus methotrexate as second-line therapy for 12 months. Tofacitinib was generally well tolerated during ≤114 months’ treatment, with most adverse events of mild or moderate severity. The tolerability profile of tofacitinib was generally similar to that of biological DMARDs (bDMARDs), with infections and infestations the most common (AEs) in tofacitinib recipients. However, the incidence of herpes zoster (HZ) was higher with tofacitinib than in the general RA population, although infections were clinically manageable. When added to background methotrexate, tofacitinib was noninferior to adalimumab in terms of efficacy, and both combination therapies had generally similar tolerability profiles. Although additional comparative studies are needed to more definitively position tofacitinib relative to bDMARDs and other targeted synthetic DMARDs, current evidence indicates that oral tofacitinib is a useful option for the treatment of patients with RA. Access to the full article can be found here.© Springer International Publishing AG, part of Springer Nature 2017
