Assessing the impact of multiple sclerosis disease activity and daclizumab HYP treatment on patient-reported outcomes: Results from the SELECT trial

Background: Disease-modifying therapies (DMT) have been shown to reduce relapses and delay disability in individuals with relapsing-remitting multiple sclerosis (MS). However, these medications can cause adverse events (AE) leading to poor adherence. To better understand their clinical utility, this study examined real-life experiences with DMT in a tertiary MS clinic. Methods: A retrospective chart review (1999-2015) was conducted to evaluate the prevalence of AE and discontinuation rates of Health Canada approved DMT. Results: 445 MS patients who have used at least one DMT in their lifetime were reviewed. Among first-line injectable therapies, interferon beta (IFNβ) 1-α IM users (49.6%) were most likely to report an AE. Flu-like reactions and injection site reactions were the most commonly reported AE. Among first-line oral therapies, BG-12 users (58.5%) were most likely to report an AE. The most common AE were flushing and gastrointestinal upset. DMT that were most frequently discontinued as a result of AE were IFNβ 1-α SC (39.3%), IFNβ 1-α IM (36.8%) and BG-12 (34.6%). Conclusions: The prevalence of AE and discontinuation rate were congruent. In comparison with recent literature, this study demonstrated lower prevalence of AE but equivocal or higher discontinuation rates. This discrepancy could represent a more realistic depiction of the impact that DMT AE have on patients.

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THU0498 PATIENT-REPORTED TREATMENT BURDEN AND ITS IMPACT ON QUALITY OF LIFE IN JUVENILE IDIOPATHIC ARTHRITIS: RESULTS FROM THE PHARMACHILD REGISTRY

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.5816 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 486-487

Author(s):

A. Alongi ◽

A. Consolaro ◽

G. Vijatov-Djuric ◽

G. Filocamo ◽

O. Vougiouka ◽

...

Keyword(s):

Medication Adherence ◽

Disease Activity ◽

Patient Reported Outcomes ◽

Sleep Problems ◽

Psychosocial Health ◽

Research Support ◽

School Problems ◽

Patient Reported ◽

The Impact

Background:Juvenile Idiopathic Arthritis (JIA) patients experience impaired health and wellbeing due to multiple causes of physical and psychosocial distress, including treatment burden. Despite emerging evidence of its relevance [1], the contribution of treatment adverse events to patient-reported outcomes (PROs) in JIA has been poorly explored.Objectives:To evaluate and rank the impact of patient-reported adverse events (AEs) on overall wellbeing, health-related quality of life (HRQoL), school problems and self-reported medication adherence using data from Pharmachild, a large international JIA pharmacovigilance registry.Methods:Registry entries on 5340 prospective visits of 2251 patients enrolled till December 2018 were analyzed; all included patients were treated with at least one DMARDS or Biologic agent at the time of visit. In the Juvenile Arthritis Multidimensional Assessment Report (JAMAR), patients and parents compiled a checklist of treatments, side effects, self-reported adherence, administration difficulties and disease-related school problems occurred in the previous 4 weeks. Evaluated outcomes included patient acceptable symptom state (PASS), VAS-measured patient assessment of overall wellbeing (PGA) and HRQoL, assessed through the physical health (PhH) and psychosocial health (PsH) subscales. The relationships between AEs and PROs were tested through generalized linear models, accounting for disease activity and symptoms levels. Bayesian Networks were used to explore the causal effects of specific AEs on outcomes to disentangle the confounding role of disease status.Results:AEs were reported in 22.9% of visits. For similar levels of physician global assessment (MD global), patient-assessed disease activity, pain and function, patients reporting AEs had worse PGA, PsH, and lower probability of reaching PASS (fig. 1, all p-values <0.001). The impact of AEs on PGA was small but not trivial (effect size η20.031) and appears to be mediated by effects on PsH and school problems (p <0.001). Non-linear regression modelling revealed a significant moderating effect of MD global levels < 2.5 on the relationship between AEs and PGA (p 0.003), indicating that the impact of AEs is higher for lower disease activity states. AEs predicted self-reported medication adherence (p<0.001), even when adjusted for the number of administered treatments. In the Bayesian network model, mood swing and sleep problems emerged as the most influential items affecting PsH, (respectively, total effect 2.62 and 1.25, both p< 0.001). Fig. 2 shows the total standardized effect of specific AEs on mean PsH levels. Nausea had the highest impact on treatment adherence (total effect -0.0541, p <0.001), being the only AE directly linked to drug refusal.Conclusion:AEs have a measurable effect on the wellbeing and psychosocial health of JIA patients, particularly when disease activity is low, and significantly affect school activity and medication adherence. Mood swings and sleep problems show the strongest influence on HRQoL. Addressing AEs appears important to reduce disease impact, improve patients’ satisfaction and therapeutic compliance.References: :[1]Weitzman, Elissa R., et al. Journal of patient-reported outcomes 2.1 (2018): 1.Acknowledgments:for the Paediatric Rheumatology International Trials Organisation (PRINTO)Disclosure of Interests: :Alessandra Alongi: None declared, Alessandro Consolaro Grant/research support from: Pfizer Inc., AlfaSigma, Speakers bureau: AbbVie, Gordana Vijatov-Djuric: None declared, Giovanni Filocamo: None declared, Olga Vougiouka: None declared, Alma Nunzia Olivieri: None declared, Cristina Herrera Mora: None declared, Wolfgang Emminger: None declared, Angelo Ravelli: None declared, Nicolino Ruperto Grant/research support from: Bristol-Myers Squibb, Eli Lily, F Hoffmann-La Roche, GlaxoSmithKline, Janssen, Novartis, Pfizer, Sobi (paid to institution), Consultant of: Ablynx, AbbVie, AstraZeneca-Medimmune, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lily, EMD Serono, GlaxoSmithKline, Hoffmann-La Roche, Janssen, Merck, Novartis, Pfizer, R-Pharma, Sanofi, Servier, Sinergie, Sobi, Takeda, Speakers bureau: Ablynx, AbbVie, AstraZeneca-Medimmune, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lily, EMD Serono, GlaxoSmithKline, Hoffmann-La Roche, Janssen, Merck, Novartis, Pfizer, R-Pharma, Sanofi, Servier, Sinergie, Sobi, Takeda

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Responder definition of the Multiple Sclerosis Impact Scale physical impact subscale for patients with physical worsening

Multiple Sclerosis Journal ◽

10.1177/1352458514530489 ◽

2014 ◽

Vol 20 (13) ◽

pp. 1753-1760 ◽

Cited By ~ 15

Author(s):

Glenn A Phillips ◽

Kathleen W Wyrwich ◽

Shien Guo ◽

Rossella Medori ◽

Arman Altincatal ◽

...

Keyword(s):

Multiple Sclerosis ◽

Psychological Functioning ◽

High Yield ◽

Impact Scale ◽

Patient Reported ◽

Clinically Significant ◽

Physical Impact ◽

Definition Of ◽

Select Trial ◽

The Impact

Background: The 29-item Multiple Sclerosis Impact Scale (MSIS-29) was developed to examine the impact of multiple sclerosis (MS) on physical and psychological functioning from a patient’s perspective. Objective: To determine the responder definition (RD) of the MSIS-29 physical impact subscale (PHYS) in a group of patients with relapsing–remitting MS (RRMS) participating in a clinical trial. Methods: Data from the SELECT trial comparing daclizumab high-yield process with placebo in patients with RRMS were used. Physical function was evaluated in SELECT using three patient-reported outcomes measures and the Expanded Disability Status Scale (EDSS). Anchor- and distribution-based methods were used to identify an RD for the MSIS-29. Results: Results across the anchor-based approach suggested MSIS-29 PHYS RD values of 6.91 (mean), 7.14 (median) and 7.50 (mode). Distribution-based RD estimates ranged from 6.24 to 10.40. An RD of 7.50 was selected as the most appropriate threshold for physical worsening based on corresponding changes in the EDSS (primary anchor of interest). Conclusion: These findings indicate that a ≥7.50 point worsening on the MSIS-29 PHYS is a reasonable and practical threshold for identifying patients with RRMS who have experienced a clinically significant change in the physical impact of MS.

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Association of joint space narrowing with impairment of physical function and work ability in patients with early rheumatoid arthritis: protection beyond disease control by adalimumab plus methotrexate

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2012-201620 ◽

2012 ◽

Vol 72 (7) ◽

pp. 1156-1162 ◽

Cited By ~ 40

Author(s):

Josef S Smolen ◽

Désirée M van der Heijde ◽

Edward C Keystone ◽

Ronald F van Vollenhoven ◽

Mary B Goldring ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Disease Activity ◽

Early Rheumatoid Arthritis ◽

Patient Reported Outcomes ◽

Joint Space Narrowing ◽

Controlled Trial ◽

Joint Space ◽

Protective Effects ◽

Patient Reported ◽

The Impact

ObjectivesTumour necrosis factor inhibition plus methotrexate is believed to inhibit radiographic progression independent of inflammation. This analysis assessed whether these protective effects are exerted on bone (joint erosion; JE) and/or cartilage (joint space narrowing; JSN), and what the independent effects of JE/JSN progression are on longer-term patient-reported outcomes.MethodsPREMIER was a 2-year, randomised, controlled trial of adalimumab plus methotrexate (ADA+MTX) versus the monotherapies. The impact of treatment on the relationships between time-averaged disease activity (TA-DAS28(CRP)) and changes in JE/JSN and associations of JE/JSN with the disability index of the health assessment questionnaire (HAQ-DI) at baseline and weeks 52 and 104 were assessed through non-parametric approaches of analysis of variance and quantile regression. JE/JSN association with employment status was evaluated at baseline and weeks 52 and 104 through logistic regression.ResultsIncreasing tertiles of TA-DAS28(CRP) were associated with JE and JSN progression in the monotherapy groups, a phenomenon largely absent in ADA+MTX-treated patients. Although JSN was not associated with HAQ-DI at baseline, it was at 52 and 104 weeks. In contrast, JE was not associated with HAQ-DI at any time point examined. Odds of being employed at baseline, 52 weeks and 104 weeks were significantly associated with lower JSN, but not JE, scores.ConclusionsADA+MTX inhibited both JE and JSN progression independently of disease activity. JSN played a more prominent role in patient-reported outcomes than JE. Preventing the onset or worsening of JSN probably represents a critical aspect of effective disease management of early rheumatoid arthritis patients.

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Certolizumab pegol plus methotrexate provides broad relief from the burden of rheumatoid arthritis: analysis of patient-reported outcomes from the RAPID 2 trial

Annals of the Rheumatic Diseases ◽

10.1136/ard.2010.143586 ◽

2011 ◽

Vol 70 (6) ◽

pp. 996-1002 ◽

Cited By ~ 44

Author(s):

Vibeke Strand ◽

Josef S Smolen ◽

Ronald F van Vollenhoven ◽

Philip Mease ◽

Gerd R Burmester ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Disease Activity ◽

Physical Function ◽

Clinical Outcomes ◽

Patient Reported Outcomes ◽

Short Form ◽

Certolizumab Pegol ◽

Number Needed To Treat ◽

Patient Reported ◽

The Impact

ObjectiveTo assess the impact of certolizumab pegol (CZP) on patient-reported outcomes (PROs) in rheumatoid arthritis (RA), and to interpret these results using number needed to treat (NNT), and associations between PRO responses and longer term outcomes.MethodsA total of 619 patients with active RA were randomised to CZP 200 or 400 mg, or placebo plus methotrexate (MTX). PROs assessed included pain, patient's global assessment of disease activity (PtGA), physical function, fatigue and health-related quality of life. Treatment impact on PROs, NNT to achieve simultaneous improvements in multiple PROs and correlations between PROs were calculated. Times to onset of improvements greater than or equal to minimum clinically important differences (MCIDs) in pain as a determinant of clinical outcomes at week 24 were compared between week 6 and 12 responders, and in patients with improvements in pain ≥MCID at week 12 (week 12 responders/non-responders).ResultsCZP 200 and 400 mg plus MTX were associated with rapid, clinically meaningful improvements in all PROs. The NNT for subjects to report changes ≥MCID in up to five PROs was two to three, and five for all six PROs (pain, PtGA, physical function, fatigue and short-form 36-item Physical and Mental Component Summary Scores). More patients with improvements ≥MCID in pain at week 6 than those at week 12 had lower disease activity at week 24. Week 12 pain responders had better clinical outcomes at week 24 than non-responders.ConclusionsThe data demonstrate that CZP provides broad relief from the burden of RA.Trial registration numberNCT00160602.

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AB0188 DO PATIENT-REPORTED OUTCOMES IN RHEUMATOID ARTHRITIS REFLECT DISEASE ACTIVITY?

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.4123 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 1118.2-1119

Author(s):

K. Ben Abdelghani ◽

H. Boussaa ◽

S. Miladi ◽

M. Sellami ◽

L. Souabni ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Disease Activity ◽

Patient Reported Outcomes ◽

Morning Stiffness ◽

Objective Assessment ◽

Disease State ◽

Spontaneous Pain ◽

Patient Reported ◽

The Mean ◽

The Impact

Background:Patient-reported outcomes (PROs) reflect the patient’s perspective and are used in rheumatoid arthritis (RA) routine clinical practice. However, PROs may be associated with other aspects of health, such as psychological distress or comorbidities, which leads to situations of discordance with objective RA assessments.Objectives:The aim of this study was to determine whether PROs were associated with objective assessment of disease activity.Methods:We conducted a cross-sectional study including patients with RA (ACR/EULAR 2010). Demographic data were collected. The following PROs were assessed: number of nocturnal awakenings, morning stiffness duration, estimation of spontaneous pain and fatigue by Visual Analog Scale (VAS), and global patient assessment (GPA). In addition, patients rated their current satisfaction with their disease state according to the Austrian school mark system (PATSAT: 1=excellent, 2=good, 3=average, 4=moderate (fair), 5=unsatisfactory). Disease activity was assessed using the 28-joint disease activity score with erythrocyte sedimentation rate (DAS28 ESR) and C reactive protein (DAS28 CRP). We used Cohen’s kappa (κ) to determine the agreement between PATSAT and DAS28 ESR. The κ result was interpreted as follows: values ≤ 0 as indicating no agreement and 0.01–0.20 as none to slight, 0.21–0.40 as fair, 0.41– 0.60 as moderate, 0.61–0.80 as substantial, and 0.81–1.00 as almost perfect agreement. A p-value inferior to 0.05 was considered significant.Results:We included 54 patients (45 women and nine men) with a mean age of 55±11 years old [23-69]. The mean disease duration was 9.9±5.9 years [0-20]. The mean number of nocturnal awakenings was 1.1 [0-4] and the mean morning stiffness duration was 25.1 minutes [0-120]. The mean GPA was 5.3±2.2 cm [0-10]. The mean pain VAS was 5.4±2.2 cm [0-10] and the mean fatigue VAS was 4±2.5 cm [0-8]. None of the patients described his disease state as ‘excellent’. It was considered ‘good’ in 23.1% of cases, ‘average’ in 36.5% of cases, and ‘moderate’ to ‘unsatisfactory’ in 40.4% of cases.The mean ESR and CRP were 46.3±29.3 mm [5-120] and 15.8 mg/l [0.6-100] respectively. The mean DAS28 ESR was 4.68±1.35 [1.50-7.16] and the mean DAS28 CRP was 3.9±1.1 [1.02-6.05].A significant positive correlation was noted between both DAS28 ESR and DAS28 CRP and, number of nocturnal awakenings (r=0.385, p=0.013 and r=0.448, p=0.002), morning stiffness duration (r=0.495, p=0.001 and r=0.617, p<0.001), GPA (r=0.485, p<0.001 and r=0.530, p<0.001), and pain VAS (r=0.594, p<0.001 and r=0.598, p<0.001). No correlation was found between the two scores and fatigue VAS.No significant agreement was noted between PATSAT and DAS28 ESR (κ=0.077, p=0.478).Conclusion:PROs showed moderate to strong correlation with disease activity scores. The timely and effective use of PROs could encourage physicians to focus more on the impact of RA on patients and how patients are feeling. This in turn would facilitate shared decision making between patients and physicians.Disclosure of Interests:None declared

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