Abstract
Background
This study sought to evaluate the efficacy and safety of tofacitinib in patients with rheumatoid arthritis with distinct treatment histories.
Methods
Pooled phase II/III trial ...data from patients who received tofacitinib 5 or 10 mg twice daily or placebo, as monotherapy or with conventional synthetic (cs) disease-modifying antirheumatic drugs (DMARDs), were analyzed post hoc. Separate evaluations were conducted for populations with a prior inadequate response (IR) to: 1) non-methotrexate (MTX) csDMARDs only (non-MTX csDMARD-IR;
n
= 537); 2) MTX (MTX-IR;
n
= 3113); and 3) biologic (b)DMARDs (bDMARD-IR;
n
= 782). Efficacy outcomes included rates of response (American College of Rheumatology 20/50/70% response criteria) and remission (Disease Activity Score in 28 joints derived from 4 measures, erythrocyte sedimentation rate DAS28-4(ESR) < 2.6) at month 3, and changes from baseline in DAS28-4(ESR) and Health Assessment Questionnaire–Disability Index scores. Safety was assessed up to month 24.
Results
At month 3, efficacy was generally improved with tofacitinib (both doses) vs placebo in each population. Generally, efficacy outcomes with tofacitinib were numerically more favorable in non-MTX csDMARD-IR vs MTX-IR or bDMARD-IR patients. Over 24 months, crude incidence rates for adverse events (AEs), serious AEs, and discontinuations due to AEs were generally numerically lower in non-MTX csDMARD-IR and MTX-IR vs bDMARD-IR populations; rates for AEs of special interest were generally similar across populations.
Conclusions
Tofacitinib provided clinical benefit across patients with rheumatoid arthritis with a range of prior treatment experience but may have greater efficacy and an improved benefit/risk profile in those with fewer prior treatments.
Trial registration
NCT00147498/NCT00413660/NCT00550446/NCT00603512/NCT00687193/NCT00976599/NCT01359150/NCT00847613/NCT00814307/NCT00853385/NCT00960440/NCT01039688/NCT00856544.
Objective. To compare the efficacy and tolerability of tofacitinib, an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA), as monotherapy and combined with disease-modifying ...antirheumatic drugs (DMARDs) versus biological DMARDs (bDMARDs) and other novel DMARDs for second-line moderate-to-severe rheumatoid arthritis (RA) patients by means of a systematic literature review (SLR) and network meta-analysis (NMA). Methods. MEDLINE®, EMBASE®, and Cochrane Central Register of Controlled Trials were searched to identify randomized clinical trials (RCTs) published between 1990 and March 2015. Efficacy data based on American College of Rheumatology (ACR) response criteria, improvements in the Health Assessment Questionnaire Disability Index (HAQ-DI) at 6 months, and discontinuation rates due to adverse events were analyzed by means of Bayesian NMAs. Results. 45 RCTs were identified, the majority of which demonstrated a low risk of bias. Tofacitinib 5 mg twice daily (BID) and 10 mg BID monotherapy exhibited comparable efficacy and discontinuation rates due to adverse events versus other monotherapies. Tofacitinib 5 mg BID and 10 mg BID + DMARDs or methotrexate (MTX) were mostly comparable to other combination therapies in terms of efficacy and discontinuation due to adverse events. Conclusion. In most cases, tofacitinib had similar efficacy and discontinuation rates due to adverse events compared to biologic DMARDs.
ObjectiveTo describe the efficacy of tofacitinib in reducing pain in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) or ankylosing spondylitis (AS) in a post-hoc analysis of ...randomised controlled trials.MethodsData were collected from patients in seven tofacitinib studies: six phase III (four RA, two PsA) and one phase II study (AS), and grouped into five analysis populations based on rheumatic disease diagnosis and category of prior inadequate response (IR) to treatment: conventional synthetic disease-modifying antirheumatic drugs-IR (RA and PsA), tumour necrosis factor inhibitors-IR (RA and PsA), or non-steroidal anti-inflammatory drugs-IR (AS). Only patients who received tofacitinib 5 or 10 mg twice daily or placebo were included. Pain assessments included: Patient’s Assessment of Arthritis Pain, Short-Form Health Survey 36v2 Question (Q)7 and Bodily Pain domain, Ankylosing Spondylitis Quality of Life Q9 and Q14, EuroQol Five Dimensions Pain/Discomfort dimension and Bath Ankylosing Spondylitis Disease Activity Index Q2 and Q3. Data were reported to month 6 (placebo to month 3) in the RA and PsA populations, and week 12 (tofacitinib and placebo) in the AS population.ResultsOverall, 3330 patients were included in this analysis. In the RA and PsA populations, pain improvements in tofacitinib-treated patients compared with placebo were observed at the earliest time point assessed and at month 3 (maintained to month 6). In the AS population, pain improvements compared with placebo were observed at week 12.ConclusionTofacitinib was associated with rapid and sustained improvements across multiple pain measures in patients with inflammatory rheumatic musculoskeletal diseases.
ObjectivesTo report the efficacy, safety and patient-reported outcome measures (PROs) of tofacitinib modified-release 11 mg once daily plus methotrexate in patients with rheumatoid arthritis (RA) ...from the open-label phase of Oral Rheumatoid Arthritis Trial (ORAL) Shift.MethodsORAL Shift was a global, 48-week, phase 3b/4 withdrawal study in patients with moderate to severe RA and an inadequate response to methotrexate. Patients received open-label tofacitinib modified-release 11 mg once daily plus methotrexate; those who achieved low disease activity (LDA; Clinical Disease Activity Index (CDAI)≤10) at week 24 were randomised to receive blinded tofacitinib 11 mg once daily plus placebo (ie, blinded methotrexate withdrawal) or continue with blinded tofacitinib 11 mg once daily plus methotrexate for another 24 weeks. Efficacy, PROs and safety from the open-label phase are reported descriptively.ResultsFollowing screening, 694 patients were enrolled and received tofacitinib plus methotrexate in the open-label phase. At week 24, 527 (84.5%) patients achieved CDAI-defined LDA. Improvements from baseline to weeks 12 and 24 were generally observed for all efficacy outcomes (including measures of disease activity, and response, LDA and remission rates) and PROs. Adverse events (AEs), serious AEs and discontinuations due to AEs were reported by 362 (52.2%), 20 (2.9%) and 41 (5.9%) patients, respectively. No deaths were reported.ConclusionsTofacitinib modified-release 11 mg once daily plus methotrexate conferred improvements in disease activity measures, functional outcomes and PROs, with most (84.5%) patients achieving CDAI-defined LDA after 24 weeks of open-label treatment; the safety profile was generally consistent with the historic safety profile of tofacitinib.Funded by Pfizer Inc; NCT02831855.
Background and Aims
A noninterventional prospective study was performed in Colombia and Peru. The aim was to describe the impact of access to treatment on Patient‐reported outcomes (PRO) in patients ...with Rheumatoid arthritis (RA) after failure to conventional disease‐modifying antirheumatic drugs (DMARDs) in real‐life conditions.
Methods
The impact of access to treatment was measured by access barriers, time to supply (TtS) and interruption evaluating their effect in changes of PROs between baseline and 6‐month follow‐up between February 2017 and November 2019. The association of access to care with disease activity, functional status, health‐related quality of life was assessed using bivariate and multivariable analysis. Results are expressed in least mean difference; TtS in mean number of days for delivery of treatment at baseline. Variability measures were standard deviation and standard error.
Results
One hundred seventy patients were recruited, 70 treated with tofacitinib and 100 with biological DMARDs. Thirty‐nine patients reported access barriers. The mean of TtS was 23 ± 38.83 days. The difference from baseline to 6‐month visit in PROs were affected by access barriers and interruptions. There was not statistically significant difference in the of PRO's score among visits in patients that reported delay of supply of more than 23 days compared to patients with less days of delay.
Conclusion
This study suggested the access to treatment can affect the response to the treatment at 6 months of follow‐up. There seems to be no effect in the PROs for delay of TtS during the studied period.
To evaluate the effect of tofacitinib (TOF) on American College of Rheumatology (ACR) response criteria components in patients with rheumatoid arthritis (RA).
This post hoc analysis pooled data from ...RA phase III randomized controlled trials (RCTs) assessing TOF 5 or 10 mg BID, adalimumab (ADA), or placebo, with conventional synthetic disease-modifying antirheumatic drugs, and a phase IIIb/IV RCT assessing TOF 5 mg BID monotherapy, TOF 5 mg BID with methotrexate (MTX), or ADA with MTX. Outcomes included proportions of patients achieving ACR20/50/70 responses and ≥ 20/50/70% improvement rates in ACR components at week 2 and months 1, 3, and 6; and mean percent improvement in ACR components and Clinical or Simplified Disease Activity Index (CDAI or SDAI) low disease activity or remission rates, at month 3, for ACR20/50/70 responders.
Across treatment groups, ≥ 20/50/70% improvement rates were numerically higher for most physician- vs patient-reported measures. In phase III RCTs, at earlier timepoints, ≥ 50/70% improvements in patient global assessment of disease activity, pain, and physician global assessment were similar. Among ACR20 responders receiving TOF, mean percent improvements for tender and swollen joint counts were > 70% at month 3. CDAI/SDAI remission was achieved at month 3 by 27.8-45.0% of ACR70 responders receiving TOF.
Among ACR20 responders treated with TOF, physician-reported components particularly exceeded 20% response improvement. At month 3, disease state generally did not corroborate ACR70 response criteria. Divergences between physician- and patient-reported measures highlight the importance of identifying appropriate patient-reported outcome targets to manage RA symptoms in clinical practice. (ClinicalTrials.gov: NCT00847613/NCT00856544/NCT00853385/NCT02187055).
Abstract
Objective
Tofacitinib is an oral Janus kinase inhibitor for treatment of RA. We compared tofacitinib modified-release (MR) 11 mg once daily (QD) with tofacitinib immediate-release (IR) 5 mg ...twice daily (BID) in Japanese patients with RA and inadequate response to MTX.
Methods
Phase III, randomized, double-blind, double-dummy, 12-week study. Patients were randomized to tofacitinib MR 11 mg QD (n = 104) or IR 5 mg BID (n = 105), with stable MTX. Compliance was based on returned pill counts. The primary objective was to demonstrate non-inferiority of MR 11 mg QD to IR 5 mg BID. Non-inferiority was declared if the upper bound of the two-sided 95% CI for the difference in change from baseline in DAS28-4(CRP) at week 12 was <0.6.
Results
At week 12, with tofacitinib MR 11 mg QD and IR 5 mg BID, respectively, the change from baseline in least squares mean DAS28-4(CRP) was −2.43 and −2.85; the mean difference was 0.43 (95% CI 0.17, 0.69). Non-inferiority of MR 11 mg QD to IR 5 mg BID was not met. Improvement of DAS28-4(CRP) ⩾1.2 was observed in 89 and 85% of patients, respectively, corresponding to a clinically important, significant change in both groups. The frequency of adverse events (52.9 and 51.4%, respectively) and serious adverse events (4.8 and 3.8%, respectively) was generally similar between treatments. No deaths were reported.
Conclusion
Non-inferiority of MR 11 mg QD to IR 5 mg BID was not met in this study. However, clinically meaningful improvements in RA were observed with both tofacitinib formulations in Japanese patients. The safety profile was similar with both formulations.
Trial registration
ClinicalTrials.gov, http://clinicaltrials.gov, NCT02281552.
The Vitiligo Area Scoring Index (VASI) is a tool for measuring repigmentation after patients undergo vitiligo treatment, offering a standardized, quantitative scale without the need for specialized ...equipment. For large multicentre trials that require multiple raters, VASI must be consistently applied to generate interpretable data; therefore, a method for assessing rater reliability would improve data integrity for large clinical studies of vitiligo. This study aimed to assess a method for determining the reliability of VASI raters by evaluating raters of different levels of experience relative to a gold standard.
Digital evidence Tatjana, Lukic
Zbornik radova (Pravni fakultet u Novom Sadu),
2012, Letnik:
46, Številka:
2
Journal Article
Recenzirano
Odprti dostop
Although computer makes human activities faster and easier, innovating and creating new forms of work and other kinds of activities, it also influenced the criminal activity. The development of ...information technology directly affects the development of computer forensics without which, it can not even imagine the discovering and proving the computer offences and apprehending the perpetrator. Information technology and computer forensic allows us to detect and prove the crimes committed by computer and capture the perpetrators. Computer forensics is a type of forensics which can be defined as a process of collecting, preserving, analyzing and presenting digital evidence in court proceedings. Bearing in mind, that combat against crime, in which computers appear as an asset or object of the offense, requires knowledge of digital evidence as well as specific rules and procedures, the author in this article specifically addresses the issues of digital evidence, forensic (computer) investigation, specific rules and procedures for detecting, fixing and collecting digital evidence and use of this type of evidence in criminal proceedings. The author also delas with international standards regarding digital evidence and cyber-space investigation.
The fight against modern forms of crime such as organized crime, terrorism and other very serious crimes caused not only modification of procedural principles and procedural rules, but also the ...necessity of re-examination of evidence in terms of introducing new evidence in criminal proceedings. Given that the prevention, detection and proving in cases of mentioned offenses represent the systemic issue and that the efficiency is caused by cohesion of preventive and repressive mechanisms in each strategy of preventing and combating serious crimes, the more often raised question, aroused from the practice, is the issue of the use of information gathered by the police or security services as evidence in criminal proceedings. In addition, there is the issue of use of illegal evidence, the ways in which these evidence are defined in some jurisdictions and which are the legal consequences of their use in judicial decision, whether it is based only on them, or on some other evidence beside them. The author addresses the issues of necessity and justification for use of information of security services as evidence in criminal proceedings, their definition and difference with respect to data, experiences and practices in other countries and of course their use as evidence in criminal proceedings of Serbia. Also, the paper addresses the Criminal Intelligence Analytics, exchange of information between the competent authorities at national and international level.
PDF
