Oral Janus Kinase Research Articles

Clinical effectiveness and safety of baricitinib for the treatment of juvenile idiopathic arthritis-associated uveitis or chronic anterior antinuclear antibody-positive uveitis: study protocol for an open-label, adalimumab active-controlled phase 3 clinical trial (JUVE-BRIGHT)

BackgroundJuvenile idiopathic arthritis (JIA) is the most common pediatric rheumatic disease and the most common systemic disorder associated with uveitis in childhood. Uveitis is more common in JIA patients who are antinuclear antibody (ANA)-positive, have an early-onset disease, and have oligoarticular arthritis. JIA-associated uveitis (JIA-uveitis) is typically anterior, chronic, bilateral, nongranulomatous, and asymptomatic. Visual outcomes in JIA-uveitis have improved with current screening and treatment options; however, many patients fail to respond or do not achieve long-lasting remission. Baricitinib, an oral selective Janus kinase (JAK)1 and 2 inhibitor, may impact key cytokines implicated in the pathogenesis of JIA-uveitis or ANA-positive uveitis, representing a potential novel treatment option for disease management.MethodsThe multicenter, phase 3 trial will be conducted using an open-label Bayesian design. The study will enroll at least 20 and up to 40 patients aged 2 to <18 years with active JIA-uveitis or chronic ANA-positive uveitis without systemic features. At least 20 patients who have had an inadequate response or intolerance to methotrexate (MTX-IR), but not biologic disease-modifying antirheumatic drugs (bDMARDs), will be randomized (1:1) to open-label baricitinib or adalimumab. Approximately 20 additional patients who are MTX-IR or bDMARD inadequate responders will receive baricitinib treatment. Patients will be treated with once daily oral baricitinib at a fixed dose by age group (4 mg for patients aged ≥6 to <18 years and 2 mg for patients <6 years) or adalimumab (20 mg for patients weighing <30 kg and 40 mg for patients ≥30 kg) as a subcutaneous injection every 2 weeks. Treatment with stable background conventional synthetic DMARDs, low-dose corticosteroids, and/or nonsteroidal anti-inflammatory drugs is allowed. The primary endpoint is the proportion of patients with response at week 24. Patients may continue treatment for up to 5 years.DiscussionThis is the first pediatric clinical trial to assess the clinical effectiveness and safety of a JAK inhibitor in JIA-uveitis or chronic ANA-positive uveitis. A novel Bayesian design is used to assess the efficacy of baricitinib, including an adalimumab reference arm, in this small patient population with unmet medical need.Trial registrationEudraCT 2019-000119-10. Registered on January 4, 2019; NCT04088409. Registered on September 12, 2019

Worldwide post-marketing safety surveillance experience with tofacitinib in ulcerative colitis.

SummaryBackgroundTofacitinib is an oral Janus kinase inhibitor for the treatment of ulcerative colitis (UC). Post‐marketing surveillance (PMS) is an important part of monitoring adverse events (AEs).AimsTo report an analysis of PMS case safety reports for tofacitinib in patients with UCMethodsWorldwide tofacitinib PMS reports received in the Pfizer safety database from 30 May 2018 (first regulatory approval) to 25 August 2020 were analysed. The type and estimated reporting rate (RR) of serious AEs of interest, including infection, gastrointestinal, vascular, respiratory, neoplasm and cardiac events, were reviewed. Patient‐years of exposure (PY) was estimated based on worldwide sales data and the calculated daily regimens of tofacitinib 5 or 10 mg twice daily, immediate‐ or extended‐release formulations.ResultsDuring the 27‐month reporting period, worldwide post‐marketing exposure to tofacitinib was 8916 PY. Overall, 4226 case reports were received and included 12 103 AEs, of which 1839 were serious AEs (SAEs). Among the cases reported, 1141 (27.0%) included an SAE and 18 (0.4%) were fatal. The RR (per 100 PY) for SAEs of interest by Medical Dictionary for Regulatory Activities System Organ Class were 3.28 for infections, 1.26 for vascular disorders, 0.74 for respiratory disorders, 0.55 for neoplasms and 0.50 for cardiac disorders.ConclusionsThe types of AEs were consistent with those reported in tofacitinib clinical trials. Most reported AEs were non‐serious. Limitations of PMS reports and reliance on estimated RRs due to lack of precise values for exposure, required for incidence rate calculation, should be considered when interpreting these results.

Incidence and risk factors for herpes zoster in patients with rheumatoid arthritis receiving upadacitinib: a pooled analysis of six phase III clinical trials

BackgroundUpadacitinib (UPA) is an oral Janus kinase (JAK) inhibitor approved for the treatment of rheumatoid arthritis (RA). JAK inhibitors have been associated with an increased risk of herpes zoster (HZ)...

Janus Kinase Inhibitors: Hope for Biotherapy in Sub-Saharan Africa?

Introduction: Tofacitinib is an oral Janus Kinase (JAK) inhibitor used in the treatment of rheumatoid arthritis (RA) and in many other conditions [1-3]. After promising results in clinical and preclinical trials, Tofacitinib was extensively evaluated in pivotal trials in 2012 and its efficacy on demonstrated structural damage [4]. Thus, Tofacitinib has been approved for the treatment of patients with RA who have an inadequate response to methotrexate [5]. Biologics are used routinely in many countries but remain difficult to access in sub-Saharan Africa [6]. The cost of biotherapies, their side effects, in particular infectious ones, and their presentation in injectable form constitute a brake on the use of these new treatments. The advent of a new therapy administered by bone would represent an excellent alternative for Africa. We thus report the case of a patient who failed conventional treatments and who has benefited from Tofacitinib (Xeljanz 5mg®).

Cost-Effectiveness of Baricitinib Compared With Standard of Care: A Modeling Study in Hospitalized Patients With COVID-19 in the United States

PurposeIn the Phase III COV-BARRIER (Efficacy and Safety of Baricitinib for the Treatment of Hospitalised Adults With COVID-19) trial, treatment with baricitinib, an oral selective Janus kinase 1/2 inhibitor, in addition to standard of care (SOC), was associated with significantly reduced mortality over 28 days in hospitalized patients with coronavirus disease–2019 (COVID-19), with a safety profile similar to that of SOC alone. This study assessed the cost-effectiveness of baricitinib + SOC versus SOC alone (which included systemic corticosteroids and remdesivir) in hospitalized patients with COVID-19 in the United States. MethodsAn economic model was developed to simulate inpatients' stay, discharge to postacute care, and recovery. Costs modeled included payor costs, hospital costs, and indirect costs. Benefits modeled included life-years (LYs) gained, quality-adjusted life-years (QALYs) gained, deaths avoided, and use of mechanical ventilation avoided. The primary analysis was performed from a payor perspective over a lifetime horizon; a secondary analysis was performed from a hospital perspective. The base-case analysis modeled the numeric differences in treatment effectiveness observed in the COV-BARRIER trial. Scenario analyses were also performed in which the clinical benefit of baricitinib was limited to the statistically significant reduction in mortality demonstrated in the trial. FindingsIn the base-case payor perspective model, an incremental total cost of 17,276 US dollars (USD), total QALYs gained of 0.6703, and total LYs gained of 0.837 were found with baricitinib + SOC compared with SOC alone. With the addition of baricitinib, survival was increased by 5.1% and the use of mechanical ventilation was reduced by 1.6%. The base-case incremental cost-effectiveness ratios were 25,774 USD/QALY gained and 20,638 USD/LY gained; a “mortality-only” scenario analysis yielded similar results of 26,862 USD/QALY gained and 21,433 USD/LY gained. From the hospital perspective, combination treatment with baricitinib + SOC was more effective and less costly than was SOC alone in the base case, with an incremental cost of 38,964 USD per death avoided in the mortality-only scenario. ImplicationsIn hospitalized patients with COVID-19 in the United States, the addition of baricitinib to SOC was cost-effective. Cost-effectiveness was demonstrated from both the payor and the hospital perspectives. These findings were robust to sensitivity analysis and to conservative assumptions limiting the clinical benefits of baricitinib to the statistically significant reduction in mortality demonstrated in the COV-BARRIER trial.

Case Report: Home-based Management of Severe COVID-19 with Low-dose Tofacitinib

ABSTRACT.Human lives and nations’ economies have been adversely affected worldwide by the COVID-19 pandemic. The hyperinflammatory state associated with the disease may be related to mortality. Systemic glucocorticoid is the first-line therapy for cytokine storm. Various immunomodulatory drugs such as tocilizumab and baricitinib have been used in those not responding to glucocorticoid monotherapy. Amid the peak crisis of COVID-19 in India, there was an extreme paucity of medications, oxygen, and hospital beds. We describe three patients with COVID-19 who received low-dose tofacitinib (an oral Janus kinase inhibitor) in addition to moderate-dose glucocorticoid. These patients were treated at their homes, as the hospitals were short of beds. Rapid reduction in hypoxemia along with gradual resolution of other signs of the disease were observed. The results are reassuring regarding the feasibility of managing of severe COVID-19 outside the hospital setting when healthcare resources are overwhelmed by pandemic-related caseload.

S710 Efficacy of High Dose Tofacitinib in Refractory Ulcerative Colitis Patients

Introduction: Tofacitinib is an oral small molecule Janus kinase inhibitor approved for the treatment of adults with moderate to severe ulcerative colitis (UC) who have failed or are intolerant to anti-TNF agent-based therapy. However, many patients fail to fully respond to standard dose of therapy. In some cases increasing the therapy dose may help however there is concern of potential side effects. Our study assessed the safety and efficacy of UC patients to tofacitinib with standard dose (SD) and high dose (HD) treatment. HD was defined as immediate release dosing more than 10 mg twice daily or extended release dosing more than 22 mg daily. Methods: This is a retrospective single-center study of all UC patients who were treated with tofacitinib. Clinical response was evaluated using the Mayo score and Ulcerative Colitis Activity Index (UCAI) and endoscopic activity was assessed with endoscopic Mayo scoring. Documentation of tofacitinib doses as well as combined biologic therapy was made. Any adverse events were documented. Results: Seventy UC patients had been treated with tofacitinib, with 21 on HD therapy. Both populations were predominantly female (approximately 60%) with mean age of 41 and 35.6, and predominant left-sided colon disease activity 25(51%) and 15(71%), in the SD and HD groups, respectively. All had previously failed treatment with at least one biologic, with approximately 70% in each group failing 2 or more. Approximately 50% of patients in both groups were treated with tofacitinib monotherapy. Vedolizumab and infliximab were the most common combination biologic agents. All the HD and SD patients who improved achieved clinical remission. The average time to clinical remission was longer in the HD group, which was expected due to the highly refractory nature of their disease. An important consideration is that 15(45%) SD patients and 1(4.8%) HD patient in the clinically improved groups were de-escalated to maintenance dosing or completely off tofacitinib therapy. Adverse events in the study were reported in 3(4%) patients, all occurring in the SD group and included lower extremity DVT formation (with uncontrolled disease activity accompanied by hospitalization), skin rash (face and trunk), and excessive bloating. No adverse events were reported in the HD group. Conclusion: The findings from this study suggest that tofacitinib can benefit UC patients who have failed multiple prior biologics with HD dosing as a potential short term option with low risk of adverse events.Figure 1.: Graphical representation of temporal trends of biologics utilization as a first line therapy in patients with IBD.Table 1.: Adjusted odds ratio and adjusted means for selected variables in patients with IBD and chronic depression compared to patients with IBD and no chronic depression.

050 Impact of Renal Impairment on the Pharmacokinetics of Abrocitinib and Its Metabolites EQ

Abrocitinib, a once-daily oral Janus kinase 1 selective inhibitor, has shown efficacy and safety in previous studies for treating moderate-to-severe atopic dermatitis (AD). Abrocitinib is primarily eliminated via the liver, but its major circulating metabolites are eliminated mainly by renal excretion. In this phase 1, nonrandomized, open-label, single-dose (200 mg) study (NCT03660241), we evaluated the impact of renal impairment on the pharmacokinetics, safety, and tolerability of abrocitinib and its metabolites in 23 subjects with different degrees of renal function (ie, normal renal function, moderate impairment, and severe impairment).

A pooled analysis of serious infections and herpes zoster-related disease in Asian patients with rheumatoid arthritis treated with peficitinib (ASP015K) over a median of 3 years.

To analyse serious infection (SI) and herpes zoster-related disease (HZD) during long-term treatment of rheumatoid arthritis with the oral Janus kinase inhibitor, peficitinib (ASP015K). This was a post hoc analysis of pooled data from one Phase 2b study and two Phase 3 studies and final data from a long-term extension study of peficitinib in Asian rheumatoid arthritis patients. Two pooled datasets were analysed (Phase 3 studies and Phase 2/3 studies). Univariate and multivariate Cox regression analyses explored relationships between exposure-adjusted incidence rate of SI and HZD, peficitinib dose, and baseline factors. Total peficitinib exposure for 1052 patients receiving once-daily peficitinib in the pooled Phase 2/3 Asian studies was 2998.9 patient-years. Exposure-adjusted incidence rates (95% confidence interval) of SI and HZD were 2.7 (2.2, 3.4) and 6.9 (6.0, 8.0) per 100 patient-years, respectively, in pooled Phase 2/3 studies. Advanced age was prognostic for SI and HZD, while baseline prednisolone dose was prognostic for SI. There was no temporal relationship between either adverse event and prolonged peficitinib administration. As expected in this peficitinib-treated population, older patients had increased risk of SI and HZD, and those receiving higher prednisolone doses had increased risk of SI.

Itch as Major Mediator of Effect of Tofacitinib on Health-Related Quality of Life in Psoriatic Arthritis: A Mediation Analysis.

Patients with psoriatic arthritis (PsA) experience impaired health-related quality of life (HRQoL). Tofacitinib is an oral Janus kinase inhibitor for the treatment of PsA, which has been associated with improvements in dermatologic endpoints in patients with PsA. To assess the extent to which tofacitinib affects patient HRQoL via improvements in dermatologic symptoms, including itch, data were pooled from patients with PsA who received tofacitinib in phase III studies (NCT01866668 and NCT01882439). Mediation modeling assessed the indirect effects (via Itch Severity Item [ISI] and Physician’s Global Assessment of Psoriasis [PGA-PsO]) and direct effects (via all other factors) of tofacitinib treatment on dermatology-specific HRQoL (measured by Dermatology Life Quality Index [DLQI]). In the initial model, the treatment effect on DLQI was largely mediated by itch (ISI; p < 0.0001) and PGA-PsO (p < 0.01). The model was re-specified to assess the indirect effects only of itch and PGA-PsO on DLQI. Here, 17.7% of the treatment effect on DLQI was attributable to PGA-PsO (p = 0.0006), and 82.3% to itch (p < 0.0001). Tofacitinib-dependent improvements in DLQI were primarily mediated by itch relief, in addition to improvements in PGA-PsO.

Efficacy and safety of baricitinib for the treatment of hospitalised adults with COVID-19 (COV-BARRIER): a randomised, double-blind, parallel-group, placebo-controlled phase 3 trial

BackgroundBaricitinib is an oral selective Janus kinase 1/2 inhibitor with known anti-inflammatory properties. This study evaluates the efficacy and safety of baricitinib in combination with standard of care for the treatment of hospitalised adults with COVID-19.MethodsIn this phase 3, double-blind, randomised, placebo-controlled trial, participants were enrolled from 101 centres across 12 countries in Asia, Europe, North America, and South America. Hospitalised adults with COVID-19 receiving standard of care were randomly assigned (1:1) to receive once-daily baricitinib (4 mg) or matched placebo for up to 14 days. Standard of care included systemic corticosteroids, such as dexamethasone, and antivirals, including remdesivir. The composite primary endpoint was the proportion who progressed to high-flow oxygen, non-invasive ventilation, invasive mechanical ventilation, or death by day 28, assessed in the intention-to-treat population. All-cause mortality by day 28 was a key secondary endpoint, and all-cause mortality by day 60 was an exploratory endpoint; both were assessed in the intention-to-treat population. Safety analyses were done in the safety population defined as all randomly allocated participants who received at least one dose of study drug and who were not lost to follow-up before the first post-baseline visit. This study is registered with ClinicalTrials.gov, NCT04421027.FindingsBetween June 11, 2020, and Jan 15, 2021, 1525 participants were randomly assigned to the baricitinib group (n=764) or the placebo group (n=761). 1204 (79·3%) of 1518 participants with available data were receiving systemic corticosteroids at baseline, of whom 1099 (91·3%) were on dexamethasone; 287 (18·9%) participants were receiving remdesivir. Overall, 27·8% of participants receiving baricitinib and 30·5% receiving placebo progressed to meet the primary endpoint (odds ratio 0·85 [95% CI 0·67 to 1·08], p=0·18), with an absolute risk difference of −2·7 percentage points (95% CI −7·3 to 1·9). The 28-day all-cause mortality was 8% (n=62) for baricitinib and 13% (n=100) for placebo (hazard ratio [HR] 0·57 [95% CI 0·41–0·78]; nominal p=0·0018), a 38·2% relative reduction in mortality; one additional death was prevented per 20 baricitinib-treated participants. The 60-day all-cause mortality was 10% (n=79) for baricitinib and 15% (n=116) for placebo (HR 0·62 [95% CI 0·47–0·83]; p=0·0050). The frequencies of serious adverse events (110 [15%] of 750 in the baricitinib group vs 135 [18%] of 752 in the placebo group), serious infections (64 [9%] vs 74 [10%]), and venous thromboembolic events (20 [3%] vs 19 [3%]) were similar between the two groups.InterpretationAlthough there was no significant reduction in the frequency of disease progression overall, treatment with baricitinib in addition to standard of care (including dexamethasone) had a similar safety profile to that of standard of care alone, and was associated with reduced mortality in hospitalised adults with COVID-19.FundingEli Lilly and Company.TranslationsFor the French, Japanese, Portuguese, Russian and Spanish translations of the abstract see Supplementary Materials section.

Patient- and physician-reported outcomes from two phase 3 randomized studies (RAJ3 and RAJ4) of peficitinib (ASP015K) in Asian patients with rheumatoid arthritis

BackgroundPeficitinib (ASP015K), a novel oral Janus kinase inhibitor, has demonstrated efficacy and safety in the treatment of patients with rheumatoid arthritis (RA). This study evaluated the effect of peficitinib on patient- and physician-reported outcomes in Asian patients with RA and an inadequate response to prior disease-modifying antirheumatic drugs (DMARDs).MethodsPatients from two randomized, placebo-controlled, double-blind, phase 3 trials (RAJ3 and RAJ4) received once-daily peficitinib 100 mg, peficitinib 150 mg, or placebo, alone or in combination with DMARDs (RAJ3), or in combination with methotrexate (RAJ4). Mean changes in Work Productivity and Activity Impairment (WPAI) questionnaire domain scores from baseline, and percentages of patients achieving minimal clinically important differences (MCIDs) for patient- and physician-reported outcomes (WPAI, Health Assessment Questionnaire – Disability Index [HAQ-DI], and Subject’s Global Assessment of Pain [SGAP]), and Physician’s Global Assessment of disease activity (PGA) were evaluated at weeks 4, 8, 12, and 12/early termination (ET).ResultsData from 1025 patients were analyzed. At week 12/ET in both studies, patients who received peficitinib 100 mg or 150 mg reported significantly improved WPAI domain scores from baseline (except for absenteeism in RAJ4) compared with placebo (both doses, p<0.05). A higher proportion of peficitinib- versus placebo-treated patients achieved MCID in WPAI, HAQ-DI, SGAP, and PGA in studies RAJ3 and RAJ4. Significant differences with peficitinib versus placebo were evident in both studies as early as week 4 in HAQ-DI (peficitinib 150 mg only), SGAP, and PGA, and week 8 in WPAI loss of work productivity and daily activity impairment. At week 12/ET, significantly higher proportions of patients receiving peficitinib versus placebo achieved MCID in HAQ-DI, SGAP, PGA, and WPAI domains of presenteeism (RAJ3 only), loss of work productivity (RAJ3 only), and daily activity impairment (p<0.05 for all comparisons).ConclusionsPeficitinib 100 mg or 150 mg administered daily over 12 weeks resulted in clinically meaningful improvements in outcomes that are important to RA patients, including pain, physical function, and work productivity and activity. These observations were reinforced through similar improvements in physicians’ rating of disease activity.Trial registrationRAJ3: ClinicalTrials.gov, NCT02308163, registered 4 December 2014.RAJ4: ClinicalTrials.gov, NCT02305849, registered 3 December 2014.

25977 Selected infection topics in adult patients with moderate-to-severe atopic dermatitis treated with baricitinib

Background: Patients with moderate-to-severe atopic dermatitis (AD) are at increased risk of infections due to a defective skin barrier and immunologic dysregulation. Baricitinib, an oral Janus kinase (JAK)1/JAK2 inhibitor, is being investigated as a treatment for moderate-to-severe AD. Because baricitinib may increase the risk of developing infections, we assessed incidence rates (IRs) in patients treated with baricitinib vs placebo.

27050 Efficacy of baricitinib 2-mg stratified by baseline body surface area in adults with moderate-to-severe atopic dermatitis

Background: Baricitinib, an oral Janus kinase (JAK)1/JAK2 inhibitor, improved disease severity in adults with moderate-to-severe atopic dermatitis (AD) in multiple Phase 3 trials. The objective of this post-hoc analysis was to evaluate the impact of baseline body surface area (BSA) on clinical responses to baricitinib monotherapy.

27582 Abrocitinib improves work productivity through improvement in pruritus and sleep: Results from the JADE MONO-2 study in patients with moderate-to-severe atopic dermatitis (AD)

Background: Pruritus is the hallmark symptom of AD, which has considerable impact on patient quality of life. However, the relationships between pruritus, sleep, and work productivity in AD have not been established. Abrocitinib, an oral once-daily Janus kinase 1 selective inhibitor, improved these outcomes in patients with moderate-to-severe AD in JADE MONO-2 (NCT03575871).

26691 Rapid and concurrent improvements in the signs and symptoms of atopic dermatitis with baricitinib in the phase 3 study, BREEZE-AD5

Baricitinib (BARI), an oral selective Janus kinase (JAK)1/JAK2 inhibitor, was evaluated in adult patients with moderate-to-severe atopic dermatitis (AD) who were intolerant or inadequate responders to topical therapy in the US- and Canadian-based placebo (PBO)-controlled Phase 3 trial, BREEZE-AD5 (NCT03435081). The objective of this analysis was to assess the onset and magnitude of changes across all disease dimensions (clinician-based and patient-reported outcomes) for the first 4 weeks of treatment in this monotherapy trial. Patients (N = 440) were randomized 1:1:1 to once-daily PBO or BARI (1-mg or 2-mg). At baseline, topical and systemic AD therapies were not allowed but could be used for rescue; data after rescue or discontinuation were considered missing. Least-squares mean change from baseline to Week 1 through Week 4 were compared between treatments using mixed model repeated measure analysis for the following: Eczema Area and Severity Index (EASI), Itch Numeric Rating Scale (NRS), Skin Pain NRS, AD Sleep Scale (ADSS) Item 2 (frequency of nighttime awakenings), Dermatology Life Quality Index (DLQI), and Patient Oriented Eczema Measure (POEM). Statistically significant improvements (P ˂ .05) in EASI, Itch NRS, Skin Pain NRS, ADSS Item 2, POEM, and DLQI were observed by Week 1 for both BARI doses compared with PBO. Statistically significant improvements (P ˂ .05) were maintained to Week 4 for both BARI doses, except with BARI 1 mg vs PBO for ADSS Item 2 (P = .055). BARI resulted in rapid and concurrent improvements in EASI, itch, sleep disturbance, DLQI, and POEM, with statistically significant improvements seen by Week 1.

27560 Interpreting the relationship between pruritus, sleep, and work productivity: Results from JADE MONO-2

Background: Patients with moderate-to-severe atopic dermatitis (AD) treated with abrocitinib, an oral once-daily Janus kinase 1 selective inhibitor, reported greater improvement in pruritus, sleep, and work productivity than placebo-treated patients in JADE MONO-2 (NCT03575871). We investigated the relationship among these outcomes.

26670 The contribution of itch and skin severity improvements to the Dermatology Life Quality Index in patients with atopic dermatitis in a baricitinib phase 3 study, BREEZE-AD5

BREEZE-AD5 (NCT03435081), a placebo (PBO)-controlled, phase 3, monotherapy trial, demonstrated the safety and efficacy of baricitinib (BARI), an oral selective Janus kinase 1/2 (JAK1/JAK2) inhibitor, for the treatment of moderate-to-severe atopic dermatitis in US and Canadian adults with previously inadequate or intolerable responses to topical therapy. This post hoc, multiple mediator analysis of BREEZE-AD5 analyzed whether improvement in itch (measured by the change from baseline in a numeric rating scale) or in skin severity (measured by the change from baseline in Eczema Area and Severity Index [EASI] or in Body Surface Area [BSA]) mediated the treatment effect over PBO on changes in the Dermatology Life Quality Index (DLQI).

Filgotinib in Rheumatoid Arthritis: A Profile of Its Use

Filgotinib (Jyseleca®), an oral Janus kinase (JAK) inhibitor, is approved as monotherapy or in combination with methotrexate to treat moderate to severe active rheumatoid arthritis (RA) in adults who have an inadequate response or intolerance to one or more disease-modifying antirheumatic drugs (DMARDs). In phase 3 trials, once-daily filgotinib was generally well tolerated and associated with an improvement in RA signs and symptoms as well as physical function in patients with an inadequate response to ongoing methotrexate, an inadequate response to ongoing conventional synthetic DMARDs plus an inadequate response or intolerance to prior biologic DMARDs, or limited or no prior exposure to methotrexate. In addition, filgotinib was noninferior to adalimumab in terms of low disease activity response rate (DAS28-CRP ≤ 3.2) in patients with an inadequate response to methotrexate. Filgotinib also appeared to inhibit the radiographic progression of joint damage and led to low disease activity or disease remission (DAS28-CRP < 2.6). Filgotinib showed sustained efficacy, and the safety profile of filgotinib longer term was similar to that in the phase 2 and 3 trials.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40261-021-01055-0.

Tofacitinib: Real-World Data and Treatment Persistence in Rheumatoid Arthritis.

Tofacitinib is an oral Janus kinase (JAK) inhibitor indicated for the treatment of rheumatoid arthritis (RA). The efficacy and safety/tolerability of tofacitinib have been extensively evaluated as monotherapy and combination therapy in multiple, randomised, multicentre studies in patients with RA. Tofacitinib as monotherapy (as first- and second-line treatment) or as combination with methotrexate (MTX) or other csDMARDs as second- and third-line treatment is effective and generally well tolerated in patients with RA. This article focuses on recent real-world evidence investigating the effectiveness, treatment persistence and safety/tolerability of tofacitinib in patients with RA. With this purpose, a literature review was conducted from April 2018 up to October 2020 for the effectiveness, persistence and safety of tofacitinib for the treatment of RA, primarily focusing on real-world studies. These retrospective and prospective and observational studies demonstrate the effectiveness of tofacitinib, thus supporting pivotal data from the clinical trial programme. Treatment persistence was generally comparable to that of biologic disease-modifying anti-rheumatic drugs. Safety findings in these observational studies were consistent with the known safety profile of the approved dose of 5 mg twice daily.