Objectives. The optimal therapeutic trial duration of anti-TNF-α therapy is currently unknown. The British Society for Rheumatology (BSR) guidance states that non-response at 3 months warrants ...re-evaluation of treatment and recommends not to persist beyond 6 months. The National Institute for Health and Clinical Excellence (NICE) specifies treatment continuation if response is achieved by 6 months, yet the European League against Rheumatism (EULAR) and the American College of Rheumatology (ACR) maintain a 3 month cut-off. No evidence exists to support a 6 month therapeutic trial over 3 months. Thus, we undertook a study to evaluate the proportion of patients who failed to meet NICE response criteria at 3 months but obtained this by 6 months, and to identify predictive factors for this. Methods. Patients who commenced anti-TNF-α therapy for RA were studied, counting those who switched to a second or third agent separately for each instigation of therapy (n = 244). Response at 3 and 6 months was defined according to NICE criteria as a ≥1.2 reduction in Disease Activity Score (DAS28). Results. Of the 189 patients with available 3 month DAS28 responses, 149 fulfilled response criteria. Of the 40 who failed, 27 continued treatment, of whom 21 were available for follow-up at 6 months. Out of the 21 patients, 12 (57%; 95% CI 36, 78) achieved a response at this time. This data set was too small to investigate predictors of response at 6 months. Conclusions. A substantial proportion of patients who fail NICE response criteria at 3 months and continue on treatment to 6 months achieve a response. These results support a 6 month therapeutic trial over 3 months.
ObjectiveEvaluate the effect of upadacitinib on pain outcomes in patients with active psoriatic arthritis (PsA) or ankylosing spondylitis (AS) across 3 randomised trials (SELECT-PsA 1 and 2 for PsA; ...SELECT-AXIS 1 for AS).MethodsPatients were randomised to upadacitinib 15 mg once daily or placebo (all 3 studies), or adalimumab 40 mg every other week (SELECT-PsA 1 only). Pain outcomes included proportion of patients achieving ≥30%, ≥50% and ≥70% reduction from baseline in patient global assessment of pain and other end points.ResultsA higher proportion of patients receiving upadacitinib versus placebo achieved ≥30%, ≥50% and ≥70% reduction in pain end points as early as week 2; these improvements with upadacitinib were generally sustained or increased through year 1 (PsA 1/2 studies: 64%/48%, 58%/42% and 38%/22%, respectively; SELECT-AXIS 1 study: 76%, 72% and 54%). Results were similar with adalimumab in PsA 1 (59%, 49% and 32%). Patients who switched from placebo to upadacitinib 15 mg were able to reach a similar level of improvement as the continuous upadacitinib groups by year 1 (PsA 1/2 studies: 46%–60%, 35%–49% and 15%–34%; AS study: 83%, 72% and 46%). Results were similar with other pain end points.ConclusionRapid and sustained improvements in pain outcomes across several end points were consistently shown with upadacitinib over 1 year in patients with active PsA or AS who had either inadequate response to prior non-biologic or biologic disease-modifying antirheumatic drugs (PsA studies) or were biologic-naïve with inadequate response to non-steroidal anti-inflammatory drugs (AS study).
Biologic disease modifying anti-rheumatic drugs have transformed the management of rheumatoid arthritis (RA) since their introduction into clinical practice over a decade ago. Following large-scale ...clinical trials, a number of biologics, with different mechanisms of action, have been licensed for the condition. In this review, we will summarise the current evidence for biologic use in RA with an emphasis on their efficacy and tolerability. In addition, we will provide a commentary on the current limitations and unmet needs in this area and discuss the future of biologic intervention.
Introduction
Patients with rheumatoid arthritis (RA) who are treated with adalimumab (ADA) are offered a proprietary patient support program (PSP, AbbVie Care
®
). The main objective of this study ...was to examine the effectiveness of ADA on RA treatment course over time in the context of PSP utilization.
Methods
PASSION was a 78-week post-marketing observational study of RA patients with an insufficient response to ≥1 DMARD newly initiating ADA in routine clinical care that was conducted in Europe, Israel, Mexico, Puerto Rico, and Australia. One prior biologic DMARD was allowed. The primary endpoint was percentage of patients achieving the minimal clinically important difference (MCID; improvement of ≥0.22 compared to baseline) in Health Assessment Questionnaire (HAQ) Disability Index (HAQ-DI) at week 78. Additionally, multiple clinical and patient-reported outcomes (PROs) were evaluated over time. Patients were categorized based on their participation in the PSP: ever (PSP users) vs. never (PSP non-users). Safety events were monitored throughout the study.
Results
Overall, 42.8% of PSP users achieved the MCID in HAQ-DI at week 78 (improvement of at least 0.22 compared to baseline). From 1025 enrolled, 48.7% of patients were PSP users while treated with ADA. The percentage of patients achieving MCID in the HAQ-DI was higher in PSP users vs. PSP non-users (48.1 vs. 37.8%) at week 78 (
p
< 0.001, NRI). Most of the studied clinical outcomes and PROs showed significant improvements (
p
< 0.05) from baseline to week 78 favoring PSP users over PSP non-users.
Conclusions
In patients with moderate-to-severe RA who initiated ADA, improvements in clinical, functional, and PROs were achieved in real-world settings with significantly greater improvements among PSP users in comparison with PSP non-users.
Funding
AbbVie.
Trial registration
: ClinicalTrials.gov identifier, NCT01383421.
Abstract
Objectives
Small molecule tyrosine kinase inhibitors smTKI, comprising mostly of Janus kinase (JAK) and to a lesser extent, spleen tyrosine kinase (SyK) inhibitors modulate the cytokine ...receptor-mediated intracellular signal cascade, and are an effective treatment for autoimmune diseases and malignancies. As smTKI are novel, long-term safety is uncertain. Due to increasing use, characterization of their true adverse event profile is critical.
Methods
We performed a systematic review and meta-analysis of all published trial data on the pulmonary and serious adverse effects of smTKIs in autoimmune disease. EMBASE, MEDLINE, CENTRAL and Pneumotox databases were searched up to April 2019 for randomized controlled trials, observational studies and post marketing surveillance, comparing any smTKI with placebo or another therapy, or as monotherapy at different doses. Primary outcomes comprised of any respiratory complications including upper and lower respiratory tract infections (URTI, LRTI), influenza, pneumonia, opportunistic respiratory infections, drug-induced interstitial lung disease, pulmonary embolism and lung neoplasm.
Results
We identified 4667 citations for screening, and selected 319 studies for full text review. Seventy-nine studies were analysed, including 47 randomized controlled trials, 25 observational studies and seven post-marketing surveillance studies, comprising 159 652 participants. There were significantly increased risks of URTI risk difference (RD) 0.03; 95% CI: 0.01, 0.05; P = 0.00; 36 studies, 14 724 participants, LRTI (RD 0.01; 95% CI: 0.00, 0.02; P = 0.02; 24 studies, 12 302 participants), influenza (RD 0.01; 95% CI: 0.00, 0.01; P = 0.04; 22 studies, 10 684 participants), and pneumonia (RD 0.00; 95% CI: 0.00, 0.01; P = 0.02; 33 studies, 15 511 participants). No increased risk was found for other respiratory complications, including pulmonary embolism.
Conclusion
SmTKI increases the risk of non-opportunistic respiratory infections compared with placebo. The risk of any serious pulmonary adverse events is low.
ObjectivesDetermine the impact of 24-week risankizumab (RZB) versus placebo (PBO) on patient-reported outcomes (PROs) in patients with psoriatic arthritis (PsA) and inadequate response to one or two ...biologics (Bio-IR) and/or ≥1 conventional synthetic disease-modifying antirheumatic drug (csDMARD-IR).MethodsPatients in the Phase 3 trial, KEEPsAKE 2, were randomised (1:1) to RZB 150 mg or PBO by subcutaneous injection. PROs assessed: 36-Item Short-Form Health Survey (SF-36), Functional Assessment of Chronic Illness Therapy—Fatigue (FACIT-Fatigue), Patient’s Assessment of Pain by visual analogue scale (VAS), Patient’s global assessment of disease activity (PtGA), EuroQoL-5 Dimension-5 Level (EQ-5D-5L) and Work Productivity and Activity Impairment—PsA (WPAI-PsA). Least squares mean change from baseline at week 24 was compared between RZB versus PBO by mixed-effects repeated regression modelling.ResultsAt week 24, RZB versus PBO treatment resulted in significant differences (95% CIs) in mean change from baseline in ranked secondary endpoints SF-36 physical component summary score (3.9 (2.4 to 5.3); p<0.001) and FACIT-Fatigue (2.2 (0.6 to 3.9); p=0.009) and improvements in pain (–8.1 (–12.8 to –3.5)), PtGA (–8.8 (–13.5 to –4.2)) and EQ-5D-5L index (0.08 (0.04 to 0.11)) and VAS (5.9 (1.9 to 9.8)) (all nominal p<0.01). More RZB-treated versus PBO-treated patients reported improvements from baseline at week 24 in 7 of 8 SF-36 subdomains (nominal p<0.05). At week 24, more RZB-treated versus PBO-treated patients reported improvements in 3 of 4 WPAI-PsA domains (nominal p≤0.01).ConclusionOverall, RBZ treatment resulted in improvements in pain, fatigue, health-related quality of life and ability to perform work in Bio-IR and/or csDMARD-IR patients with PsA.Trial registration numberNCT03671148.
Background: Rheumatoid arthritis (RA) is a chronic, inflammatory, systemic disease, which negatively influences patients' quality of life, work productivity and longevity. Current therapies include ...traditional and biologic disease-modifying antirheumatic drugs (DMARDs). Although these are effective for many, a substantial proportion of patients fail to respond to these agents, suffer from loss of efficacy and/or experience unpleasant side effects, highlighting the need for alternatives. Objectives/methods: To address how a greater proportion of RA patients may potentially achieve disease remission, we reviewed data on IL-6 as a therapeutic target. Results/conclusions: IL-6 is an important driver of RA pathogenesis, mediating both articular and systemic effects of the disease. Tocilizumab, an inhibitor of the IL-6 receptor (IL-6R), is beneficial in treating RA in a variety of clinical contexts. Evidence to date supports the use of tocilizumab, as monotherapy or combination therapy, as an effective approach to the treatment of RA. Here, we discuss key efficacy and safety data from the recently published Phase III trials.
Metabolic myopathies: a guide and update for clinicians Burr, Marian L; Roos, Jonathan C; Östör, Andrew JK
Current opinion in rheumatology,
2008-November, 2008-Nov, 2008-11-00, 20081101, Letnik:
20, Številka:
6
Journal Article
PURPOSE OF REVIEWThe present review will focus on the clinical features, and recent advances in the investigation and treatment, of metabolic muscle disease. The aim is to present a summary of this ...vast and complex topic emphasizing key points of relevance to nonspecialists in the field. Salient examples from each category will be highlighted to illustrate characteristic features and potential sources of diagnostic confusion. The general approach to management will then be outlined.
RECENT FINDINGSAwareness of these diseases has grown over recent years, as has appreciation of their variable clinical presentation. Many of the precise genetic and biochemical abnormalities underlying these conditions have been elucidated and novel enzyme defects continue to be discovered. Perhaps the greatest progress, however, has been made in the management of disease. Advances in tandem mass spectrometry techniques have facilitated the introduction of nationwide neonatal screening programmes for a large number of metabolic disorders. Enzyme replacement in Pompe disease has proved successful, improving outcome in a hitherto untreatable condition. Progress towards gene therapy, perhaps the ultimate goal, has been made in animal models.
SUMMARYAlthough individually rare, the metabolic myopathies together constitute a significant group of disabling and potentially life-threatening disorders. Appropriate investigations, timely treatment and genetic counselling are paramount to ameliorate the short and long-term consequences of disease.
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