In this opinion paper, we argue that global health crises are also information crises. Using as an example the coronavirus disease 2019 (COVID‐19) epidemic, we (a) examine challenges associated with ...what we term “global information crises”; (b) recommend changes needed for the field of information science to play a leading role in such crises; and (c) propose actionable items for short‐ and long‐term research, education, and practice in information science.
To assess the safety, pharmacokinetics, and exploratory efficacy of SM04690, a novel Wnt pathway inhibitor, as a potential disease modifying treatment for knee osteoarthritis (OA).
Subjects with ...Kellgren-Lawrence grade 2–3 knee OA were randomized in successive dose-escalation cohorts to receive a knee intra-articular (IA) injection with 0.03, 0.07, or 0.23 mg SM04690, or placebo (PBO) (4:1 ratio). Safety, pharmacokinetics, efficacy (WOMAC Total/Function/Pain, Pain VAS, Physician Global Assessment MDGA, and OMERACT-OARSI Response), OA-related biomarker (P1NP, ß-CTX, and cartilage oligomeric matrix protein COMP), and radiographic/imaging data were collected at baseline and during 24-week follow-up.
61 subjects (SM04690 n = 50; PBO n = 11) enrolled. Two dose limiting toxicities (DLTs), increased pain following injection and paroxysmal tachycardia (also the single serious AE), were reported in the 0.07 mg cohort. A total of 72 AEs were reported; Sixteen (occurring in eight subjects) were considered related to study medication. There were three discontinuations; one due to an AE (0.03 mg cohort). Bone marrow edema (BME) remained constant for most subjects. No doses were excluded from further study due to DLT criteria. Plasma levels of SM04690 were below the limit of detection at all time points. At Week 24, improvements from baseline were seen in all cohorts for the exploratory measures WOMAC Total, WOMAC Function, WOMAC Pain, MDGA, Pain VAS, and OMERACT-OARSI response. Joint space width (JSW) improvement was observed in the 0.07 mg cohort (P = 0.02 vs PBO).
SM04690 appeared safe and well tolerated, with no evidence of systemic exposure. Exploratory efficacy analyses suggested positive trends for measurements of OA pain, function and disease-modifying osteoarthritis drug (DMOAD) properties.
NCT02095548.
Objectives To evaluate the efficacy and safety of certolizumab pegol (CZP) after 24 weeks in RAPID-PsA (NCT01087788), an ongoing Phase 3 trial in patients with psoriatic arthritis (PsA). Methods ...Patients were randomised 1:1:1 to placebo, 200 mg CZP every 2 weeks (Q2W) or 400 mg CZP every 4 weeks (Q4W). Patients could have had exposure to one previous tumour necrosis factor (TNF) inhibitor therapy. Primary endpoints were American College of Rheumatology 20% (ACR20) response at week 12 and modified Total Sharp Score change from baseline at week 24. Secondary endpoints included; Psoriatic Arthritis Response Criteria (PsARC) score, Health Assessment Questionnaire Disability Index (HAQ-DI), Psoriasis Area and Severity Index, Leeds Enthesitis Index, Leeds Dactylitis Index, and Modified Nail Psoriasis Severity Index. Results Of 409 patients randomised, 368 completed 24 weeks of treatment. ACR20 response was significantly greater in CZP 200 mg Q2W and 400 mg Q4W-treated patients than placebo (58.0% and 51.9% vs 24.3% (p<0.001)) at week 12, with improvements observed by week 1. There was a statistically significant improvement in physical function from baseline, measured by HAQ-DI in CZP patients compared with placebo (−0.50 vs −0.19, p<0.001) and more patients treated with CZP 200 mg Q2W and CZP 400 mg achieved an improvement in PsARC at week 24 than placebo (78.3% and 77.0% vs 33.1% (p<0.001)). Sustained improvements were observed in psoriatic skin involvement, enthesitis, dactylitis and nail disease. Higher ACR20 response with CZP was independent of prior TNF inhibitor exposure. No new safety signals were observed. Conclusions Rapid improvements in the signs and symptoms of PsA, including joints, skin, enthesitis, dactylitis and nail disease were observed across both CZP dosing regimens.
Treatment options available to patients with rheumatoid arthritis (RA) are ever-changing, and understanding the similarities and differences of efficacy and safety between different RA therapies is ...of key importance in order to facilitate treatment decisions by both the patient and physician. Very few head-to-head, peer-reviewed trials exist; instead, evidence for efficacy of treatments is often ascertained from placebo-controlled trials, registries and meta-analyses, which often do not sufficiently address the relative effectiveness of two medications.
A targeted review of indirect comparison methods, and ongoing and published clinical studies assessing the efficacy and safety, and the comparative efficacy and safety of biologic disease modifying antirheumatic drugs in RA.
Critical elements that should be considered when designing head-to head trials are described using examples of true head-to-head and placebo-controlled randomized controlled trials (RCTs). The appropriate use of head-to-head trial designs is demonstrated by reviewing different examples of well-designed clinical trials, and an overview is presented of the challenges associated with indirect comparisons. This review also examines the use of studies comparing therapies to placebo, highlighting the difficulties associated with the interpretation of these studies.
For comparative trials to contribute to evidence-based decision making in the treatment of RA, patient populations and treatment regimens as similar as possible to those used in routine clinical practice should be employed and the trial should be appropriately designed to answer the specific question asked.
Background:Tumour necrosis factor α (TNFα) is a proinflammatory cytokine involved in the pathogenesis of rheumatoid arthritis (RA). Treatment with TNFα inhibitors reduces disease activity and ...improves outcomes for patients with RA. This study evaluated the efficacy and safety of certolizumab pegol 400 mg, a novel, poly-(ethylene glycol) (PEG)ylated, Fc-free TNFα inhibitor, as monotherapy in patients with active RA.Methods:In this 24-week, multicentre, randomised, double-blind, placebo-controlled study, 220 patients previously failing ⩾1 disease-modifying antirheumatic drug (DMARD) were randomised 1:1 to receive subcutaneous certolizumab pegol 400 mg (n = 111) or placebo (n = 109) every 4 weeks. The primary endpoint was 20% improvement according to the American College of Rheumatology criteria (ACR20) at week 24. Secondary endpoints included ACR50/70 response, ACR component scores, 28-joint Disease Activity Score Erythrocyte Sedimentation Rate 3 (DAS28(ESR)3), patient-reported outcomes (including physical function, health-related quality of life (HRQoL), pain and fatigue) and safety.Results:At week 24, the ACR20 response rates were 45.5% for certolizumab pegol 400 mg every 4 weeks vs 9.3% for placebo (p<0.001). Differences for certolizumab pegol vs placebo in the ACR20 response were statistically significant as early as week 1 through to week 24 (p<0.001). Significant improvements in ACR50, ACR components, DAS28(ESR)3 and all patient-reported outcomes were also observed early with certolizumab pegol and were sustained throughout the study. Most adverse events were mild or moderate and no deaths or cases of tuberculosis were reported.Conclusions:Treatment with certolizumab pegol 400 mg monotherapy every 4 weeks effectively reduced the signs and symptoms of active RA in patients previously failing ⩾1 DMARD compared with placebo, and demonstrated an acceptable safety profile.Trial registration number:NCT00548834.
New scientific concepts, interpreted broadly, are continuously introduced in the literature, but relatively few concepts have a long‐term impact on society. The identification of such concepts is a ...challenging prediction task that would help multiple parties—including researchers and the general public—focus their attention within the vast scientific literature. In this paper we present a system that predicts the future impact of a scientific concept, represented as a technical term, based on the information available from recently published research articles. We analyze the usefulness of rich features derived from the full text of the articles through a variety of approaches, including rhetorical sentence analysis, information extraction, and time‐series analysis. The results from two large‐scale experiments with 3.8 million full‐text articles and 48 million metadata records support the conclusion that full‐text features are significantly more useful for prediction than metadata‐only features and that the most accurate predictions result from combining the metadata and full‐text features. Surprisingly, these results hold even when the metadata features are available for a much larger number of documents than are available for the full‐text features.
Among the disease-modifying drugs used to treat rheumatoid arthritis, methotrexate is increasingly regarded as the agent of first choice, because of its early onset of action and superior efficacy ...and tolerability.
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Clinical benefit with methotrexate may be seen as early as three weeks after initiating treatment,
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and the maximal improvement is generally achieved by six months.
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Although methotrexate can have toxic effects, making careful monitoring of patients necessary, most rheumatologists believe the benefits outweigh the risks. Methotrexate can diminish the activity of rheumatoid arthritis, but many patients have persistent disease even when treated with methotrexate. When this occurs, rheumatologists usually . . .
Objective
To examine the effect of certolizumab pegol (CZP) on patient‐reported outcomes (PROs) in psoriatic arthritis (PsA) patients with and without prior tumor necrosis factor (TNF) inhibitor ...exposure.
Methods
The ongoing phase III RAPID‐PsA trial was double blind and placebo controlled to week 24. Patients were randomized 1:1:1 to placebo every 2 weeks or CZP 400 mg at weeks 0, 2, and 4, followed by either CZP 200 mg every 2 weeks or CZP 400 mg every 4 weeks. PRO measures evaluated were the Health Assessment Questionnaire (HAQ) disability index (DI), health status (measured by the Short Form 36 SF‐36 health survey), Psoriatic Arthritis Quality of Life (PsAQOL), Fatigue Assessment Scale, patient assessment of pain (visual analog scale), and Dermatology Life Quality Index (DLQI). Post hoc analyses of PROs in patients with and without prior TNF inhibitor exposure were conducted. Change from baseline for all PROs was analyzed for the randomized population using analysis of covariance with last observation carried forward imputation.
Results
A total of 409 patients were randomized. Twenty percent had received a prior TNF inhibitor. Baseline demographics were similar between the treatment groups. At week 24, clinically meaningful differences in HAQ DI, SF‐36, PsAQOL, fatigue, pain, and DLQI were observed in both CZP arms versus placebo (P < 0.001), irrespective of prior TNF inhibitor exposure. More CZP‐treated patients reached SF‐36 general population norms than placebo‐treated patients.
Conclusion
Both CZP dosing schedules provided rapid improvements in PROs across multiple disease aspects in patients with PsA. The benefits of CZP treatment for health‐related quality of life were seen across generic, PsA‐specific, and dermatology‐specific measures and were observed in patients regardless of prior TNF inhibitor exposure.
Background:Repository corticotropin injection (RCI) is a naturally sourced complex mixture of adrenocorticotropic hormone analogs and other pituitary peptides approved for short-term adjunctive ...treatment of rheumatoid arthritis (RA).Objectives:This two-part, international, multicenter, placebo (PBO)-controlled study assessed the efficacy of RCI in persistently active RA patients (pts) using clinical and patient-reported outcome measures (PROMs) (ClinicalTrials.gov NCT02919761).Methods:Adults ≥18 years with persistently active RA (DAS28-ESR >3.2) despite disease-modifying anti-rheumatic drug and glucocorticoid use received open-label RCI (80 U) subcutaneously 2x/week (BIW) for 12 weeks (Part 1). Pts with DAS28-ESR <3.2 at Week (W) 12 entered the double-blind maintenance phase (Part 2) and were randomized to 80 U RCI or PBO BIW through W24. Efficacy endpoints included the proportion of pts who achieved DAS28-ESR <3.2 at W12 (primary) and maintained it through W24 (secondary). Mean changes from baseline (BL) were assessed for select PROMs (exploratory): Patient Global Assessment of Pain (PGAP); Patient Global Assessment of Disease Activity (PGADA); Health Assessment Questionnaire Disability Index (HAQ-DI); Functional Assessment of Chronic Illness Therapy – Fatigue (FACIT-F) scale; and Work Productivity and Activity Impairment (WPAI) questionnaire. Analyses used the modified intent-to-treat population (mITT-P; pts who received ≥1 dose of study drug and contributed any efficacy data).Results:In the mITT-P (N=259), 62.9% (p<0.0001) achieved DAS28-ESR <3.2 at W12 (mean BL DAS28-ESR=6.3). In Part 2 (RCI, n=77; PBO, n=76), more RCI-treated pts maintained DAS28-ESR <3.2 at W24 (62.3%, p=0.035) vs. PBO (43.4%). Clinically significant improvements in PROMs from BL were observed through W12 and sustained to W24 (Table 1), with mean changes exceeding the reported minimal clinically important difference thresholds (MCIDs) for each.Conclusion:RCI for persistently active RA resulted in clinically significant improvements in efficacy endpoints and PROMs for up to 6 months in pts who continued and discontinued RCI after 3 months of initial therapy.References:Acknowledgments:Editorial support was provided by MedLogix Communications, LLC, Itasca, Illinois, under the direction of authors and funded by Mallinckrodt Pharmaceuticals.Disclosure of Interests:Roy Fleischmann Grant/research support from: AbbVie, Akros, Amgen, AstraZeneca, Bristol-Myers Squibb, Boehringer, IngelhCentrexion, Eli Lilly, EMD Serono, Genentech, Gilead, Janssen, Merck, Nektar, Novartis, Pfizer, Regeneron Pharmaceuticals, Inc., Roche, Samsung, Sandoz, Sanofi Genzyme, Selecta, Taiho, UCB, Consultant of: AbbVie, ACEA, Amgen, Bristol-Myers Squibb, Eli Lilly, Gilead, GlaxoSmithKline, Novartis, Pfizer, Sanofi Genzyme, UCB, Daniel Furst Grant/research support from: AbbVie, Actelion, Amgen, BMS, Corbus Pharmaceuticals, the National Institutes of Health, Novartis, Pfizer, and Roche/Genentech, Consultant of: AbbVie, Actelion, Amgen, BMS, Cytori Therapeutics, Corbus Pharmaceuticals, the National Institutes of Health, Novartis, Pfizer, and Roche/Genentech, Speakers bureau: CMC Connect (McCann Health Company), George Wan Employee of: Mallinckrodt Pharmaceuticals, Mary Panaccio Employee of: Mallinckrodt Pharmaceuticals, Jingyu Liu Employee of: Mallinckrodt Pharmaceuticals, Julie Zhu Employee of: Mallinckrodt Pharmaceuticals, Richard Brasington Speakers bureau: Amgen, Mallinckrodt Pharmaceuticals, Novartis, and Pfizer
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