scholarly journals Baricitinib improves symptoms in patients with moderate-to-severe atopic dermatitis and inadequate response to topical corticosteroids: patient-reported outcomes from two randomized monotherapy phase III trials

2020 ◽  
pp. 1-10
Author(s):  
K. Reich ◽  
A. M. DeLozier ◽  
F. P. Nunes ◽  
J. P. Thyssen ◽  
L. F. Eichenfield ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
Patient Reported Outcomes ◽  
Phase Iii ◽  
Severe Atopic Dermatitis ◽  
Inadequate Response ◽  
Topical Corticosteroids ◽  
Patient Reported ◽  
Phase Iii Trials

scholarly journals Tofacitinib or adalimumab versus placebo: patient-reported outcomes from OPAL Broaden—a phase III study of active psoriatic arthritis in patients with an inadequate response to conventional synthetic disease-modifying antirheumatic drugs

RMD Open ◽  
2019 ◽  
Vol 5 (1) ◽  
pp. e000806 ◽  
Author(s):  
Vibeke Strand ◽  
Kurt de Vlam ◽  
Jose A Covarrubias-Cobos ◽  
Philip J Mease ◽  
Dafna D Gladman ◽  
...  
Keyword(s):  
Psoriatic Arthritis ◽  
Patient Reported Outcomes ◽  
Short Form ◽  
Janus Kinase ◽  
Phase Iii ◽  
Placebo Patient ◽  
Pain Patient ◽  
Inadequate Response ◽  
Patient Reported ◽  
Disease Modifying

ObjectivesTofacitinib is an oral Janus kinase inhibitor for treatment of psoriatic arthritis (PsA). We evaluated patient-reported outcomes (PROs) in patients with PsA refractory to ≥1 conventional synthetic disease-modifying antirheumatic drug (csDMARD-IR) and tumour necrosis factor inhibitor-naïve in a 12-month, phase III randomised controlled trial (OPAL Broaden [NCT01877668]).MethodsPatients (N=422) received tofacitinib 5 mg or 10 mg twice daily, adalimumab 40 mg subcutaneously every 2 weeks or placebo advancing to tofacitinib 5 mg or 10 mg twice daily at month 3. Least squares mean changes from baseline and percentages of patients reporting improvements ≥minimum clinically important differences (MCID); and scores ≥normative values in: Patient Global Assessment of disease activity (PtGA), Pain, Patient Global Joint and Skin Assessment (PGJS), Short Form-36 Health Survey version 2 (SF-36v2), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue), EuroQol 5-Dimensions-3-level questionnaire (EQ-5D-3L) and Ankylosing Spondylitis Quality of Life (ASQoL) were determined. Nominal p values were cited without multiple comparison adjustments.ResultsAt month 3, PtGA, Pain, PGJS, FACIT-Fatigue, EQ-5D-3L, ASQoL and SF-36v2 Physical Component Summary (PCS), physical functioning (PF), bodily pain (BP) and vitality domain scores exceeded placebo with both tofacitinib doses (p≤0.05); SF-36v2 social functioning with 5 mg twice daily (p≤0.05). Percentages reporting improvements ≥MCID in PtGA, Pain, PGJS, FACIT-Fatigue, ASQoL and SF-36v2 PCS, PF, BP and general health scores exceeded placebo with both tofacitinib doses (p≤0.05) and were similar with adalimumab.ConclusioncsDMARD-IR patients with active PsA reported statistically and clinically meaningful improvements in PROs with tofacitinib compared with placebo at Month 3.

scholarly journals Suggestions for improving the design of clinical trials in multiple sclerosis—results of a systematic analysis of completed phase III trials

2019 ◽  
Vol 10 (4) ◽  
pp. 425-436 ◽  
Author(s):  
Sinje Gehr ◽  
Thomas Kaiser ◽  
Reinhold Kreutz ◽  
Wolf-Dieter Ludwig ◽  
Friedemann Paul
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Trials ◽  
Patient Reported Outcomes ◽  
Progressive Multiple Sclerosis ◽  
Phase Iii ◽  
Primary Progressive Multiple Sclerosis ◽  
Systematic Overview ◽  
Patient Reported ◽  
Phase Iii Trials ◽  
Secondary Endpoints

AbstractThis manuscript reviews the primary and secondary endpoints of pivotal phase III trials with immunomodulatory drugs in multiple sclerosis (MS). Considering the limitations of previous trial designs, we propose new standards for the planning of clinical trials, taking into account latest insights into MS pathophysiology and patient-relevant aspects. Using a systematic overview of published phase III (pivotal) trials performed as part of application for drug market approval, we evaluate the following characteristics: trial duration, number of trial participants, comparators, and endpoints (primary, secondary, magnetic resonance imaging outcome, and patient-reported outcomes). From a patient perspective, the primary and secondary endpoints of clinical trials are only partially relevant. High-quality trial data pertaining to efficacy and safety that stretch beyond the time frame of pivotal trials are almost non-existent. Understanding of long-term benefits and risks of disease-modifying MS therapy is largely lacking. Concrete proposals for the trial designs of relapsing (remitting) multiple sclerosis/clinically isolated syndrome, primary progressive multiple sclerosis, and secondary progressive multiple sclerosis (e.g., study duration, mechanism of action, and choice of endpoints) are presented based on the results of the systematic overview. Given the increasing number of available immunotherapies, the therapeutic strategy in MS has shifted from a mere “relapse-prevention” approach to a personalized provision of medical care as to the choice of the appropriate drugs and their sequential application over the course of the disease. This personalized provision takes patient preferences as well as disease-related factors into consideration such as objective clinical and radiographic findings but also very burdensome symptoms such as fatigue, depression, and cognitive impairment. Future trial designs in MS will have to assign higher relevance to these patient-reported outcomes and will also have to implement surrogate measures that can serve as predictive markers for individual treatment response to new and investigational immunotherapies. This is an indispensable prerequisite to maximize the benefit of individual patients when participating in clinical trials. Moreover, such appropriate trial designs and suitable enrolment criteria that correspond to the mode of action of the study drug will facilitate targeted prevention of adverse events, thus mitigating risks for individual study participants.

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