Capacity to work is impacted by psoriatic arthritis (PsA). Our objective was to describe the course of work productivity and leisure activity in patients with PsA treated with biologic (b) and ...targeted synthetic (ts) disease-modifying antirheumatic drugs (DMARDs).
A systematic literature review identified all trials and observational studies published January 1, 2010-October 22, 2021, reporting work productivity using the Work Productivity and Activity Impairment Questionnaire (WPAI) in patients with PsA treated with b/tsDMARDs. Outcomes for WPAI domains (absenteeism, presenteeism, total work productivity, and activity impairment) were collected at baseline and time point closest to 24 weeks of treatment. A random effects meta-analysis of single means was conducted to calculate an overall absolute mean change from baseline for each WPAI domain.
Twelve studies (ten randomized controlled and two observational) assessing patients treated with adalimumab, bimekizumab, guselkumab, ixekizumab, risankizumab, secukinumab, or upadacitinib were analysed. Among 3741 employed patients, overall mean baseline scores were 11.4%, 38.7%, 42.7%, and 48.9% for absenteeism, presenteeism, total work productivity impairment, and activity impairment, respectively. Estimated absolute mean improvements (95% confidence interval) to week 24 were 2.4 percentage points (%p) (0.6, 4.1), 17.8%p (16.2,19.3), 17.6%p (15.9,19.4), and 19.3%p (17.6, 21.0) respectively, leading to a mean relative improvement of 41% for total work productivity. The change in work outcomes in the b/tsDMARDs appeared similar.
This systematic literature review and meta-analysis confirmed that patients with active PsA have a substantially reduced capacity to work and participate in leisure activities. Substantial improvements across various WPAI domains were noted after 24 weeks of b/tsDMARD treatment, especially in presenteeism, total work productivity, and activity impairment. These findings may be useful for reimbursement purposes and in the context of shared decision-making. This systematic literature review (SLR) of randomized clinical trials and observational studies of biologic (b) and targeted synthetic (ts) disease-modifying antirheumatic drugs b/tsDMARDs in patients with PsA found that at treatment introduction, patients presented with a 42.7% mean productivity loss per week as assessed by the Work Productivity and Activity Impairment (WPAI) Questionnaire. Through a meta-analysis comparing before/after values without adjustment for placebo response, we found that after 24 weeks of treatment with b/tsDMARDs, there was a mean absolute improvement of 17.6 percentage points and a mean relative improvement of 41% in total work productivity, with similar magnitudes of improvement in time spent at work and regular activities outside of work. These results provide clinical-, regulatory- and reimbursement decision-makers with data on the potential societal and socio-economic benefits of b/tsDMARDs in PsA.
We conducted a systematic review of the literature and network meta-analysis (NMA) to compare the relative effectiveness of antibiotic treatments for Clostridioides (Clostridium) difficile infection ...(CDI) including vancomycin (VCM), metronidazole (MTZ) and fidaxomicin (FDX). Eligible studies were randomised controlled trials (RCTs) including adults with any severity of CDI that was treated with VCM, MTZ or FDX. The NMA was performed using a Bayesian framework, using a fixed-effects model.
The searches identified seven publications for inclusion, which provided five RCTs for VCM versus MTZ, and three RCTs for FDX versus VCM. The NMA showed that for clinical cure rate, there was no difference for FDX versus VCM, and there was a significant difference in favour of FDX versus MTZ (odds ratio OR: 1.77; 95% credible interval CrI 1.11, 2.83). For recurrence rate, there was a significant difference in favour of FDX versus both VCM (OR: 0.50; 95% CrI: 0.37, 0.68) and MTZ (OR: 0.44; 95% CrI: 0.27, 0.72). For sustained cure (clinical cure without recurrence), there was a significant difference in favour of FDX versus VCM (OR: 1.61; 95% CrI: 1.27, 2.05) and MTZ (OR: 2.39; 95% CrI: 1.65, 3.47).
These findings suggest that FDX and VCM are effective first-line treatments for mild or moderate CDI, whereas MTZ is not, and FDX may be more effective at preventing CDI recurrence than VCM.
Objective: Doctor-shopping has significant consequences for patients and payers and can indicate misuse of drugs, polypharmacy, less continuity of care, and increased medical expenses. This study ...reviewed the literature describing doctor-shoppers in the adult population.
Methods: A systematic literature review was performed in PubMed and supplemented by a Google search of grey literature. Overall, 2885 records were identified; 43 papers served as a source of definition of a doctor-shopper, disease, treatment, patient characteristics, patient special needs, country.
Results: Definitions of doctor-shopping were heterogeneous. Overall, 40% of studies examined the use of opioids, antidepressants, or psychoactive drugs, while the others focused on chronic or frequent diseases. Most studies were conducted in countries with easy access to healthcare resources (USA, France, Taiwan, Hong Kong). The prevalence of doctor-shopping ranged from 0.5% among opioid users in the USA to 25% of patients registered at general practices in Japan. Comorbidities, active substance abuse, greater distance from healthcare facility, younger age, longer disease and poor patient satisfaction increased doctor-shopping.
Conclusions: Knowing the characteristics of doctor-shoppers may help identify such patients and reduce the associated waste of medical resources, but concerns about the misuse of drugs or healthcare resources should not prevent proper disease management.
Objective: Baloxavir marboxil (baloxavir) is the first cap-dependent endonuclease inhibitor being studied for the treatment of influenza in single oral dosing regimen. This network meta-analysis ...(NMA) evaluated the efficacy and safety of baloxavir compared to other antivirals for influenza in otherwise healthy patients.
Methods: A systematic literature review was performed on 14 November 2016 in Medline, Embase, CENTRAL, and ICHUSHI to identify randomized controlled trials assessing antivirals for influenza. A NMA including 22 trials was performed to compare the efficacy and safety of baloxavir with other antivirals.
Results: The time to alleviation of all symptoms was significantly shorter for baloxavir compared to zanamivir (difference in median time 19.96 h; 95% CrI 3.23, 39.07). The time to cessation of viral shedding was significantly shorter for baloxavir than zanamivir and oseltamivir (47.00 h; 95% CrI 28.18, 73.86 and 56.03 h 33.74, 87.86, respectively). The mean decline in virus titer from baseline to 24 h was significantly greater for baloxavir than for the other drugs. Other differences in efficacy outcomes were not significant. No significant differences were found between baloxavir and the other antivirals for safety, except total drug-related adverse events where baloxavir demonstrated a decrease compared to oseltamivir and laninamivir.
Conclusions: The NMA suggests that baloxavir demonstrated better or similar efficacy results compared to other antivirals with a comparable safety profile. Baloxavir led to a significant decrease in viral titer versus zanamivir, oseltamivir and peramivir and decreased viral shedding versus zanamivir and oseltamivir.
Purpose
To compare visual outcomes and treatment burden between intravitreally administered aflibercept (IVT-AFL) and ranibizumab (RBZ) treat-and-extend (T&E) regimens in patients with wet ...age-related macular degeneration (wAMD) at 2 years.
Methods
A systematic literature review was carried out in Medline, EMBASE, and CENTRAL in October 2018. Matching-adjusted indirect comparison (MAIC) and/or individual patient data meta-regression was used to connect ALTAIR (assessing IVT-AFL T&E) with other studies, adjusting for between-trial differences in baseline visual acuity and age or baseline visual acuity, age, and polypoidal choroidal vasculopathy (PCV) status. Sensitivity analyses were conducted to test the robustness of the results, including direct MAIC between IVT-AFL T&E (ALTAIR) and RBZ T&E (CANTREAT and TREX-AMD trials).
Results
Six randomized controlled trials (RCTs) (ALTAIR, VIEW 1 and 2, CATT, CANTREAT, and TREX) were included in the analysis. IVT-AFL T&E was assessed in one study, ALTAIR (
n
= 255), while RBZ T&E was assessed in two trials (
n
= 327). At 2 years, the median difference (95% credibility interval) between IVT-AFL T&E and RBZ T&E regarding the numbers of Early Treatment Diabetic Retinopathy Study (ETDRS) letters gained was not significant (M1: − 2.29 − 8.10, 3.58; M2: − 0.55 − 6.34, 5.29). IVT-AFL T&E was associated with significantly fewer injections than RBZ-T&E (M1: − 6.12 − 7.60, − 4.65; M2: − 5.93 − 7.42, − 4.45). Results of the sensitivity analyses were consistent with the main scenarios.
Conclusion
Patients with wAMD receiving an IVT-AFL T&E regimen achieved and maintained improvement in visual acuity with fewer injections over 2 years compared with RBZ T&E. IVT-AFL T&E may therefore serve as the optimal therapy for wAMD, as it was associated with clinical efficacy and minimized treatment burden.
Over the past decade, several drugs have been approved for the treatment of relapsed or refractory multiple myeloma (RRMM). This retrospective study, using the French National Healthcare database ...(SNDS), describes the treatment patterns and outcomes of patients with RRMM treated in real-world clinical practice in France. Patients were adults, with a diagnosis of multiple myeloma, who initiated second-line (2L) treatment approved for use in France between 2014 and 2018; this included bortezomib, carfilzomib, daratumumab, ixazomib, lenalidomide, or pomalidomide. Data were analyzed overall, by first-line (1L) autologous stem cell transplant (ASCT) status and by lenalidomide treatment status at 2L. In total, 12987 patients with RRMM were included in the study (mean age 69.5 years); 27% received an ASCT at 1L, and 30% received a lenalidomide-sparing regimen at 2L. Overall, and among the ASCT and non-ASCT subgroups, most patients received a bortezomib-based regimen at 1L, whereas lenalidomide-based regimens were most common at 2L. Among patients who received a lenalidomide-sparing regimen at 2L, this was most often a proteasome inhibitor-based regimen. Mortality rate was 26.1/100 person-years, and median (95% confidence interval) survival from 2L initiation was 32.4 (31.2–33.6) months. Survival differed by various factors, shorter survival was reported in the non-ASCT group, those receiving a lenalidomide-sparing regimen at 2L, older patients (≥ 70 years), and those with multiple comorbidities. This analysis provides insight into the real-world use of approved novel MM treatments and highlights an ongoing unmet need to improve outcomes, particularly for selected patient groups.
Background:
Patients with active axial spondyloarthritis (axSpA) exhibit more absences and lower levels of productivity in the workplace and household than the general population, which can improve ...upon treatment.
Objectives:
The objective of this study is to determine the long-term impact of achieving different levels of clinical response or disease activity on workplace and household productivity in patients with axSpA.
Design:
RAPID-axSpA (NCT01087762) was a 204-week phase III trial evaluating the safety and efficacy of certolizumab pegol (CZP) in adult patients with active axSpA.
Methods:
The impact of axSpA on workplace and household productivity was evaluated using the validated arthritis-specific Work Productivity Survey. Outcomes included the percentage of patients achieving Assessment of SpondyloArthritis International Society (ASAS) response and Ankylosing Spondylitis Disease Activity Score (ASDAS) thresholds. This post hoc study used a generalised estimating equations model to determine the association between the threshold of clinical response achieved and patient productivity.
Results:
Of 218 CZP-randomised patients, 65.1% completed week 204. At baseline, 72.0% were employed outside the home. Of the patients who were unemployed, 42.6% were unable to work due to arthritis. Achievement of higher treatment response thresholds, such as clinical remission, was associated with fewer days affected by workplace absenteeism (ASAS-partial remission: 4.0 days, ASAS40: 8.6 days, ASAS20 but not reaching ASAS40 response: 29.4 days, ASAS20 non-response: 69.2 days; ASDAS-inactive disease: 5.0 days, ASDAS-low disease activity: 15.6 days, ASDAS-high disease activity: 32.7 days, ASDAS-very high disease activity: 93.4 days). Similar associations were found for workplace presenteeism, and household absenteeism and presenteeism.
Conclusions:
Over 4 years, achievement of higher clinical response thresholds and lower levels of disease activity was associated with fewer cumulative days affected by absenteeism or presenteeism, with clinical remission associated with the greatest improvements in productivity. This highlights the importance of targeting these thresholds to limit the burden of axSpA on society and on patients’ daily lives.
Background:
Psoriatic arthritis (PsA) impacts the physical health and functional ability of patients, leading to reduced productivity. High unemployment rates and absence due to sickness have been ...reported in patients with PsA.
Objectives:
This post hoc study investigated certolizumab pegol treatment impact on workplace and household productivity in patients with PsA, and assessed whether achievement of more stringent disease control was associated with greater improvements in productivity.
Design:
RAPID-PsA was a 216-week phase III trial.
Methods:
This post hoc study used a generalised estimating equations (GEE) model to examine the disease activity association, measured using American College of Rheumatology (ACR) and Disease Activity in PSoriatic Arthritis (DAPSA), and workplace and household productivity, assessed using an arthritis-specific Work Productivity Survey (WPS). The GEE model estimated the mean cumulative number of days patients meeting different disease control criteria were affected by absenteeism or presenteeism in the workplace and household.
Results:
In all, 273 patients were randomised to certolizumab pegol and 183 (67.0%) completed Week 216. At baseline, 60.8% of patients were employed outside the home. Improved disease control, measured using ACR and DAPSA criteria, was associated with fewer cumulative days affected by workplace absenteeism through Week 216: ACR70: 4.1 days, ACR50 to <70: 7.7, ACR20 to <50: 20.9, <ACR20: 35.7; DAPSA remission (REM): 3.3, low disease activity (LDA): 9.8, moderate disease activity (MoDA): 22.4, high disease activity (HDA): 54.0. Improved disease control was also associated with fewer days affected by workplace presenteeism: ACR70: 5.6, ACR50 to <70: 19.3, ACR20 to <50: 71.2, < ACR20: 141.2; DAPSA REM: 5.7, LDA: 25.8, MoDA: 77.2, HDA: 223.6. Similar associations between greater disease control and improved productivity were observed for household absenteeism and presenteeism.
Conclusion:
This post hoc study demonstrates the cumulative workplace and household work productivity benefits for patients with PsA when achieving more stringent thresholds of disease control with certolizumab pegol treatment.
Background Wide-ranging placebo responses challenge SLE trials. This analysis aims to identify predictors of SOC+PBO response in patients with SLE. Methods Analyses used the SOC+PBO arm of the phase ...2b trial of dapirolizumab pegol (NCT02804763), a polyethylene glycol conjugated antigen-binding fragment lacking a functional Fc domain, which inhibits CD40-CD40L interaction.¹ Response was assessed by BILAG-based Composite Lupus Assessment (BICLA) response at Week 24.² Univariate/multivariate analyses were performed, with 22 previously determined potential predictors. Stepwise multivariate analysis included univariate predictors with p<0.25, using p≤0.10 as entry/stay criteria. Disease activity at screening was defined using BILAG 2004 item level scores as acute flare (worsening/new symptoms) or persistent (symptoms the same) based on the past 4 weeks compared with the prior 4 weeks; low C3/C4 was defined as below the lower limit of normal at screening. Results were supported by additional biologic clinical trial datasets. Results Univariate analysis found the following significant predictors of BICLA non-response at Week 24 (p<0.05): persistent disease (vs acute flare; p=0.003), low C3 and/or C4 (vs normal; p=0.007), low C4 (vs normal; p=0.007), low C3 (vs normal; p=0.042), and SLEDAI-2K score ≥10 (vs <10; p=0.044) (figure 1). In the multivariate stepwise analysis, significant predictors of BICLA non-response (odds ratio OR; 95% confidence interval; p<0.05) were persistent disease (vs acute flare; 0.047 0.004, 0.491; p=0.011) and low C4 (vs normal; 0.094 0.010, 0.857; p=0.036). To explore the impact of identified predictors, subgroup analyses showed a higher proportion of patients with acute flare without low C3/C4 (n=10) achieved BICLA response at Week 24 vs patients with acute flare and low C3/C4 or persistent disease activity (n=33) (80.0% vs 24.2%; p=0.005 for OR vs acute flare without low C3/C4). Conclusions Acute flare with normal complement predicted high placebo response in this analysis. Recent medical history should be considered when defining SLE study populations. Abstract LP-198 Figure 1 Univariate analysis of predictors of BICLA response at Week 24 in patients who received SOC+PBO. Anti-dsDNA: anti-double-stranded deoxyribonucleic acid; BICLA: BILAG-based Composite Lupus Assessment; BILAG: British Isles Lupus Assessment Group; CLASI: Cutaneous Lupus Erythematosus Disease Area and Severity Index; m: months; PBO: placebo; SLEDAI-2K: Systemic Lupus Erythematosus Disease Activity Index 2000; SOC: standard of care. Figure omitted. See PDF References Furie RA. Rheumatology (Oxford) 2021;60:5397–407. Wallace D. Arthritis Rheum 2011;63(Suppl 10):S885.
BackgroundAxial spondyloarthritis (axSpA) can limit work participation. Our objective was to characterise productivity in patients with axSpA, including changes after 12–16 weeks of treatment with ...biological and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs).MethodsA systematic literature review identified studies published from 1 January 2010 to 21 October 2021 reporting work productivity using the Work Productivity and Activity Impairment (WPAI) questionnaire in patients with axSpA initiating b/tsDMARDs. Baseline and Week 12–16 overall work productivity, absenteeism, presenteeism and activity impairment scores were used in a random-effects meta-analysis to calculate absolute mean change from baseline for each WPAI-domain.ResultsEleven studies in patients with axSpA who received either placebo (n=727) or treatment with adalimumab, bimekizumab, etanercept, ixekizumab, secukinumab or tofacitinib (n=994) were included. In working patients initiating a b/tsDMARD, mean baseline overall work productivity impairment, absenteeism and presenteeism scores were 52.1% (N=7 studies), 11.0% and 48.8% (N=6 studies), respectively. At Week 12–16, the pooled mean change from baseline in overall work impairment for b/tsDMARDs or placebo was −21.6% and −12.3%. When results were extrapolated to 1 year, the potential annual reductions in cost of paid and unpaid productivity loss per patient ranged from €11 962.88 to €14 293.54.ConclusionsOver 50% of employed patients with active axSpA experienced work impairment, primarily due to presenteeism. Overall work productivity improved at Weeks 12–16 to a greater extent for patients who received b/tsDMARDs than placebo. Work productivity loss was associated with a substantial cost burden, which was reduced with improvements in impairment.
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