Worse Disability Research Articles

Eculizumab monotherapy for NMOSD: Data from PREVENT and its open-label extension

During PREVENT (a phase 3, randomized, double-blind, placebo-controlled, time-to-event study) and its open-label extension (interim analysis), 33 adults with aquaporin-4 immunoglobulin G-positive neuromyelitis optica spectrum disorder (AQP4-IgG + NMOSD) received eculizumab monotherapy for a median of 2.8 years (range, 14 weeks–5.2 years). At 192 weeks (~4 years), 96% of these patients were free from adjudicated relapses (Kaplan–Meier analysis; 95% confidence interval, 75.7–99.4). During PREVENT, 95% (20/21) of patients receiving eculizumab monotherapy had no disability worsening. Eculizumab monotherapy provides effective long-term relapse prevention, relieving the chronic immunosuppression burden in patients with AQP4-IgG + NMOSD. ClinicalTrials.gov; PREVENT: NCT01892345; open-label extension: NCT02003144.

1193Developing a Multifactorial Prognostic Index in Relapsing Onset Multiple Sclerosis and Clinically Isolated Syndrome

Abstract Background Disease course in multiple sclerosis (MS) is characterised by relapses and worsening of disability. This study aims to create, from available clinical, genetic, and environmental factors; a multifactorial prognostic index (MPI) to predict disease course in MS. Methods We analysed prospectively assessed MS cases (N = 253) with 2858 repeated measurements over 10-years. Of the 253 cases, N = 219 were diagnosed as relapsing-onset, while N = 34 remained as clinically isolated syndrome by the 10th-year review. Cox regression models with Least Absolute Shrinkage and Selection Operator were used to select potential genetic, clinical, and environmental factors that are predictive of relapses and/or worsening of disability. Multivariate Cox regression models with leave-one-out cross-validation were used to construct a MPI, from which robust dynamic predictions were obtained by landmarking. The predictive performance at diagnosis was evaluated using the Kullback-Leibler and Brier prediction error curves. Results The MPI predicted a quadratic time-dynamic disease course in terms of relapses (HR = 2.16, CI: 1.74-2.68; C-index=0.85) and worsening of disability (HR = 2.74, CI: 2.00-3.76; C-index=0.76). The Kullback-Leibler and Brier dynamic prediction error curves showed reasonable performance for both short- (≤5-years from diagnosis) and long-term (>5-years from diagnosis) prognostications, respectively. Conclusions The MPI provided reliable information that is relevant for long-term prognostication and may be used as a selection criterion or risk stratification tool for clinical trials. Key messages Using relevant clinical, environmental, and genotype data, we have created a MPI for people living with MS and clinically isolated syndrome.

Long-term safety and efficacy of dimethyl fumarate for up to 13 years in patients with relapsing-remitting multiple sclerosis: Final ENDORSE study results

Background: Dimethyl fumarate (DMF) demonstrated favorable benefit–risk in relapsing-remitting multiple sclerosis (RRMS) patients in phase-III DEFINE and CONFIRM trials, and ENDORSE extension. Objective: The main aim of this study is assessing DMF safety/efficacy up to 13 years in ENDORSE. Methods: Randomized patients received DMF 240 mg twice daily or placebo (PBO; Years 0–2), then DMF (Years 3–10; continuous DMF/DMF or PBO/DMF); maximum follow-up (combined studies), 13 years. Results: By January 2020, 1736 patients enrolled/dosed in ENDORSE (median follow-up 8.76 years (ENDORSE range: 0.04–10.98) in DEFINE/CONFIRM and ENDORSE); 52% treated in ENDORSE for ⩾6 years. Overall, 551 (32%) patients experienced serious adverse events (mostly multiple sclerosis (MS) relapse or fall; one progressive multifocal leukoencephalopathy); 243 (14%) discontinued treatment due to adverse events (4% gastrointestinal (GI) disorders). Rare opportunistic infections, malignancies, and serious herpes zoster occurred, irrespective of lymphocyte count. For DMF/DMF (n = 501), overall annualized relapse rate (ARR) remained low (0.143 (95% confidence interval (CI), 0.120–0.169)), while for PBO/DMF (n = 249), ARR decreased after initiating DMF and remained low throughout (ARR 0–2 years, 0.330 (95% CI, 0.266–0.408); overall ARR (ENDORSE, 0.151 (95% CI, 0.118–0.194)). Over 10 years, 72% DMF/DMF and 73% PBO/DMF had no 24-week confirmed disability worsening. Conclusion: Sustained DMF safety/efficacy was observed in patients followed up to 13 years, supporting DMF’s positive benefit/risk profile for long-term RRMS treatment.

Long-Term Efficacy Outcomes of Natalizumab vs. Fingolimod in Patients With Highly Active Relapsing-Remitting Multiple Sclerosis: Real-World Data From a Multiple Sclerosis Reference Center.

Background: Natalizumab (NTZ) and fingolimod (FTY) are second-line disease modifying treatments (DMTs) approved for Relapsing – Remitting Multiple Sclerosis (RRMS). Few studies are available on a direct comparison between NTZ and FTY, based on post-marketing experience, with conflicting results and reporting relatively short follow-up period.Aim: We hereby report real-world experience of a MS Center with respect to NTZ vs. FTY comparison in terms of efficacy and safety, referencing long-term follow-up.Methods: We used retrospective data for all patients that received 2nd-line treatment NTZ (since May 2007) or FTY (since September 2011). Primary endpoints were, among others, annual EDSS score (mean change from baseline), time to disability worsening or improvement, Annualized Relapse Rate (ARR) after 12 and 24 months and upon total treatment duration, time to first relapse and time to radiological progression.Results: A total of 138 unmatched patients, 84 treated with NTZ and 54 treated with FTY were included. Following Propensity Score (PS) matching, 31 patients in each group were retained. Mean follow-up period for NTZ- and FTY-treated patients was 4.43 ± 0.29 and 3.59 ± 0.32 years (p = 0.057), respectively. In the matched analysis, time to disability improvement and time to disability worsening was comparable between groups. A higher proportion of patients remained free of relapse under NTZ, compared to FTY (Log Rank test p = 0.021, HR: 0.25, 95% CI: 0.08–0.8), as well as free of MRI activity (Log Rank test p = 0.006, HR: 0.26, 95% CI: 0.08–0.6). Treatment discontinuation due to MRI activity was significantly higher for FTY-treated patients compared to NTZ (Log Rank test p = 0.019, HR: 0.12, 95% CI: 0.05–0.76).Conclusion: Our results indicate toward NTZ superiority with respect to relapse and MRI activity outcomes. The fact that NTZ-treated patients may achieve long-standing clinical and radiological remission points toward the need for long follow-up data.

Treatment Escalation vs Immediate Initiation of Highly Effective Treatment for Patients With Relapsing-Remitting Multiple Sclerosis

Treatment strategies for relapsing-remitting multiple sclerosis (RRMS) vary markedly between Denmark and Sweden. The difference in the association of these national strategies with clinical outcomes is unknown. To investigate the association of national differences in disease-modifying treatment (DMT) strategies for RRMS with disability outcomes. This cohort study used data on 4861 patients from the Danish and Swedish national multiple sclerosis (MS) registries from the date of index DMT initiation (between January 1, 2013, and December 31, 2016) until the last recorded visit at time of data extraction (October 2, 2019). All MS-specific DMTs initiated during the observation period were included in the analysis. The primary study outcome was time to 24-week confirmed disability worsening. Secondary outcomes were 24-week confirmed disability improvement, milestone Expanded Disability Status Scale scores of 3 and 4, annualized relapse rate, time to first relapse, and treatment switching. Data were analyzed using inverse probability of treatment weighting-based models using a propensity score to weight and correct the comparison for the imbalance of confounders observed at baseline between the 2 countries. A total of 2700 patients from the Swedish MS registry (1867 women [69.2%]; mean [SD] age, 36.1 [9.5] years) and 2161 patients from the Danish MS registry (1472 women [68.1%]; mean [SD] age, 37.3 [9.4 years]) started a first DMT between 2013 and 2016, were included in the analysis, and were observed for a mean (SD) of 4.1 (1.5) years. A total of 1994 Danish patients (92.3%) initiated a low to moderately effective DMT (teriflunomide, 907 [42.0%]) and 165 (7.6%) initiated a highly effective DMT, whereas a total of 1769 Swedish patients (65.5%) initiated a low to moderately effective DMT (teriflunomide, 64 [2.4%]) and 931 (34.5%) initiated a highly effective DMT. The Swedish treatment strategy was associated with a 29% reduction in the rate of postbaseline 24-week confirmed disability worsening relative to the Danish treatment strategy (hazard ratio, 0.71; 95% CI, 0.57-0.90; P = .004). The Swedish treatment strategy was also associated with a 24% reduction in the rate of reaching an expanded disability status scale score of 3 (hazard ratio, 0.76; 95% CI, 0.60-0.97; P = .03) and a 25% reduction in the rate of reaching an expanded disability status scale score of 4 (hazard ratio, 0.75; 95% CI, 0.61-0.96; P = .01) relative to Danish patients. The findings of this study suggest that there is an association between differences in treatment strategies for RRMS and disability outcomes at a national level. Escalation of treatment efficacy was inferior to using more efficacious DMT as initial treatment.

Smoking, obesity, and disability worsening in PPMS: an analysis of the INFORMS original trial dataset.

Smoking and obesity are recognized modifiable risk factors associated with a higher MS incidence, but their impact on physical and cognitive disability worsening is less clear. To investigate the impact of smoking and obesity on disability worsening in primary progressive MS (PPMS). We used data from INFORMS (clinicaltrials.gov identifier: NCT00731692), a large randomized-controlled trial in PPMS to compare significant worsening on the EDSS, T25FW, NHPT, and PASAT between smokers and non-smokers, and between BMI groups, at 12, 24, and 33months of follow-up. We investigated the association of smoking and BMI at screening and the risk of disability worsening with logistic regression models. Smokers had significantly higher EDSS scores throughout the trial. EDSS was not significantly different between BMI categories. No other outcome measure was significantly different between smokers and non-smokers and between BMI categories throughout the trial. Neither smoking status nor BMI were associated with significant worsening on any outcome measure at any time point during follow-up. Despite the known effects on MS incidence, smoking and BMI were not associated with the risk of physical and cognitive disability worsening over 3 years in this well-characterized PPMS trial cohort.

Pain in rheumatoid arthritis: a seven-year follow-up study of pain distribution and factors associated with transition from and to chronic widespread pain

Objective: To study transitions from and to chronic widespread pain (CWP) over 7 years in patients with rheumatoid arthritis (RA). Method: Two postal questionnaires were sent to patients included in the BARFOT (Better Anti-Rheumatic Pharmacotherapy) study, the first in 2010 and the second in 2017. The questionnaires assessed pain, number of tender and swollen joints, functional disability, health-related quality of life (HRQoL), pharmacological treatment, lifestyle factors, and patient-reported body mass index (BMI). The responders to both questionnaires were divided into three groups according to the reported pain duration and distribution: patients having no chronic pain (NCP), chronic regional pain (CRP), and CWP. Results: In all, 953 patients answered the questionnaires at both time-points. One-third (324) of the patients reported CWP in 2010, and 140 (43%) of the patients had transition to NCP or CRP in 2017. In multivariate logistic regression models, adjusting for age, gender, and disease duration, transition from CWP was associated with normal BMI, fewer tender joints, less pain, less fatigue, fewer pain regions, less disability, better HRQoL, and biologic treatment. In 2010, 628 patients reported NCP or CRP, whereas 114 of them reported CWP in 2017. Transition to CWP was associated with female gender, obesity, more tender and swollen joints, higher pain-related variables, worse disability, and worse HRQoL. Conclusion: There are modifiable factors associated with transitions from and to CWP that could be identified. Paying attention to these factors could improve pain treatment in the management of RA.

Prognostic Accuracy of NEDA-3 in Long-term Outcomes of Multiple Sclerosis

Background and ObjectivesTo estimate the proportions of patients with relapsing-remitting multiple sclerosis who despite achieving the no evidence of disease activity-3 (NEDA-3) status in the first 2 treatment years experienced relapse-associated worsening (RAW) or progression independent from relapse activity (PIRA) in the following years.MethodsWe selected patients with NEDA-3—defined as no relapse, no disability worsening, and no MRI activity—in the first 2 years of either glatiramer acetate or interferon beta as initial treatment. We estimated the long-term probability of subsequent RAW and PIRA (considered as 2 contrasting outcomes) by cumulative incidence functions. Competing risk regressions were used to identify the baseline (i.e., at treatment start) predictors of RAW and PIRA.ResultsOf 687 patients, 224 (32.6%) had NEDA-3 in the first 2 treatment years. After a median follow-up time of 12 years from treatment start, 58 patients (26%) experienced disability accrual: 31 (14%) had RAW and 27 (12%) had PIRA. RAW was predicted by the presence of >9 T2 lesions (subdistribution hazard ratio [SHR] = 3.92, p = 0.012) and contrast-enhancing lesions (SHR = 2.38, p = 0.047) on baseline MRI scan and either temporary or permanent discontinuation of the initial treatment (SHR = 1.11, p = 0.015). PIRA was predicted by advancing age (SHR = 1.05, p = 0.036 for each year increase) and presence of ≥1 spinal cord lesion on baseline MRI scan (SHR = 4.08, p = 0.016).DiscussionThe adoption of NEDA-3 criteria led to prognostic misclassification in 1 of 4 patients. Different risk factors were associated with RAW and PIRA, suggesting alternative mechanisms for disability accrual.Classification of EvidenceThis study provides Class II evidence that in patients with RRMS who attained NEDA-3 status, subsequent RAW was associated with baseline MRI activity and discontinuation of treatment and PIRA was associated with age and the presence of baseline spinal cord lesions.

Long Covid in adults discharged from UK hospitals after Covid-19: A prospective, multicentre cohort study using the ISARIC WHO Clinical Characterisation Protocol.

BackgroundThis study sought to establish the long-term effects of Covid-19 following hospitalisation.Methods327 hospitalised participants, with SARS-CoV-2 infection were recruited into a prospective multicentre cohort study at least 3 months post-discharge. The primary outcome was self-reported recovery at least ninety days after initial Covid-19 symptom onset. Secondary outcomes included new symptoms, disability (Washington group short scale), breathlessness (MRC Dyspnoea scale) and quality of life (EQ5D-5L).Findings55% of participants reported not feeling fully recovered. 93% reported persistent symptoms, with fatigue the most common (83%), followed by breathlessness (54%). 47% reported an increase in MRC dyspnoea scale of at least one grade. New or worse disability was reported by 24% of participants. The EQ5D-5L summary index was significantly worse following acute illness (median difference 0.1 points on a scale of 0 to 1, IQR: -0.2 to 0.0). Females under the age of 50 years were five times less likely to report feeling recovered (adjusted OR 5.09, 95% CI 1.64 to 15.74), were more likely to have greater disability (adjusted OR 4.22, 95% CI 1.12 to 15.94), twice as likely to report worse fatigue (adjusted OR 2.06, 95% CI 0.81 to 3.31) and seven times more likely to become more breathless (adjusted OR 7.15, 95% CI 2.24 to 22.83) than men of the same age.InterpretationSurvivors of Covid-19 experienced long-term symptoms, new disability, increased breathlessness, and reduced quality of life. These findings were present in young, previously healthy working age adults, and were most common in younger females.FundingNational Institute for Health Research, UK Medical Research Council, Wellcome Trust, Department for International Development and the Bill and Melinda Gates Foundation.

Accuracy, Sensitivity, and Specificity of the LLIS and ULL27 in Detecting Breast Cancer-Related Lymphedema.

Breast cancer-related lymphedema occurs in up to 30% of women following axillary lymph node dissection (ALND) and less commonly following sentinel lymph node biopsy. To quantify disability in these patients, patient-reported outcome measures (PROMs) have proven useful; however, given the overlap of symptoms between ALND and lymphedema, examination of their accuracy, sensitivity, and specificity in detecting lymphedema in breast cancer patients undergoing ALND is needed. The Lymphedema Life Impact Scale (LLIS) and the Upper Limb Lymphedema 27 scale (ULL27) were administered to patients who had undergone ALND at least 2 years prior and either did or did not develop lymphedema. Survey responses and the degree of disability were compared to generate receiver operator characteristic (ROC) curves, and the sensitivity and specificity of PROMs to diagnose lymphedema were analyzed. Both PROMs were highly accurate, sensitive, and specific for detecting lymphedema. The LLIS had an accuracy of 97%, sensitivity of 100%, and specificity of 84.8% at a cutoff of ≥ 5.88 overall percent impairment score (higher scores indicate worse disability). The ULL27 had an accuracy of 93%, sensitivity of 88.6%, and specificity of 90.9% at a cutoff of ≤ 83.3 global score (lower scores indicate worse disability). The LLIS and the ULL27 appear to be highly specific for lymphedema and capable of differentiating it from symptoms resulting from ALND alone. Our findings suggest that use of these questionnaires with a threshold may be effective for diagnosing lymphedema, potentially reducing the need for frequent clinic visits and time-consuming measurements.

Toxicity and efficacy of chimeric antigen receptor T-cell therapy in patients with diffuse large B-cell lymphoma above the age of 70 years compared to younger patients - a matched control multicenter cohort study.

Data regarding efficacy and toxicity of chimeric antigen receptor T (CAR-T) cell therapy in the elderly, geriatric population are insufficient. In 2019, tisagenlecleucel and axicabtagene-ciloleucel were commercially approved for relapsed/refractory diffuse large B-cell lymphoma. From May 2019 onwards, 47 relapsed/refractory diffuse large Bcell lymphoma patients, ≥70 years underwent lymphopharesis in three Israeli centers. Elderly (n=41, mean age 76.2 years) and young (n=41, mean age 55.4 years) patients were matched based on ECOG performance status and lactose dehydrogenase levels. There were no differences in CD4/CD8 ratio (P=0.94), %CD4 naive (P=0.92), %CD8 naive (P=0.44) and exhaustion markers (both HLA-DR and PD-1) between CAR-T cell products in both cohorts. Forty-one elderly patients (87%) received CAR-T cell infusion. There were no differences in the incidence of grade ≥3 cytokine-release-syndrome (P=0.29), grade≥3 neurotoxicity (P=0.54), and duration of hospitalization (P=0.55) between elderly and younger patients. There was no difference in median D7-CAR-T cell expansion (P=0.145). Response rates were similar between the two groups (complete response 46% and partial response 17% in the elderly group, P=0.337). Non-relapse mortality at 1 and 3 months was 0 in both groups. With a median follow-up of 7 months (range, 1.3-17.2 months), 6- and 12-months progression-free and overall survival in elderly patients were 39% and 32%, and 74% and 69%, respectively. EORTC QLQ-C30 questionnaires, obtained at 1 month, showed worsening of disability and cancer-related-symptoms in elderly versus younger patients. We conclude that outcomes of CAR-T cell therapy are comparable between elderly, geriatric and younger patients, indicating that age as per se should not preclude CAR-T cell administration. Longer rehabilitation therapy is essential to improve disabilities and long-term symptoms.

Clinical outcomes of patients with multiple sclerosis treated with ocrelizumab in a US community MS center: an observational study

BackgroundTo monitor long-term outcomes of ocrelizumab treatment.ObjectiveTo evaluate safety and treatment outcomes of ocrelizumab in a community-based multiple sclerosis (MS) population.MethodsAdult patients with MS prescribed ocrelizumab were eligible. Chart reviews...

Confirmed 6-Month Disability Improvement and Worsening Correlate with Long-term Disability Outcomes in Alemtuzumab-Treated Patients with Multiple Sclerosis: Post Hoc Analysis of the CARE-MS Studies.

IntroductionIn the 2-year CARE-MS trials (NCT00530348; NCT00548405) in patients with relapsing–remitting multiple sclerosis, alemtuzumab showed superior efficacy versus subcutaneous interferon beta-1a. Efficacy was maintained in two consecutive extensions (NCT00930553; NCT02255656). This post hoc analysis compared disability outcomes over 9 years among alemtuzumab-treated patients according to whether they experienced confirmed disability improvement (CDI) or worsening (CDW) or neither CDI nor CDW.MethodsCARE-MS patients were randomized to receive two alemtuzumab courses (12 mg/day; 5 days at baseline; 3 days at 12 months), with additional as-needed 3-day courses in the extensions. CDI or CDW were defined as ≥ 1.0-point decrease or increase, respectively, in Expanded Disability Status Scale (EDSS) score from core study baseline confirmed over 6 months, assessed in patients with baseline EDSS score ≥ 2.0. Improved or stable EDSS scores were defined as ≥ 1-point decrease or ≤ 0.5-point change (either direction), respectively, from core study baseline. Functional systems (FS) scores were also assessed.ResultsOf 511 eligible patients, 43% experienced CDI and 34% experienced CDW at any time through year 9 (patients experiencing both CDI and CDW were counted in each individual group); 29% experienced neither CDI nor CDW. At year 9, patients with CDI had a −0.58-point mean EDSS score change from baseline; 88% had stable or improved EDSS scores. Improvements occurred across all FS, primarily in sensory, pyramidal, and cerebellar domains. Patients with CDW had a +1.71-point mean EDSS score change; 16% had stable or improved EDSS scores. Patients with neither CDI nor CDW had a −0.10-point mean EDSS score change; 98% had stable or improved EDSS scores.ConclusionCDI achievement at any point during the CARE-MS studies was associated with improved disability at year 9, highlighting the potential of alemtuzumab to change the multiple sclerosis course. Conversely, CDW at any point was associated with worsened disability at year 9.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40120-021-00262-3.

Pregnancy in multiple sclerosis women with relapses in the year before conception increases the risk of long-term disability worsening

Background: The influence of pregnancy on long-term disability in multiple sclerosis (MS) is still controversial. Objective: To assess the risk of long-term disability worsening after pregnancy in MS women as compared with a propensity-score (PS) matched group of MS women without pregnancy. Methods: In the setting of the Italian Pregnancy Dataset, MS patients with (pregnancy group (PG)) and without pregnancy (control group (CG)) were recruited. Time to disability worsening on the Expanded Disability Status Scale (EDSS) was assessed through a multivariable Cox regression model. Results: The PS-matching retained 230 PG and 102 CG patients. After a follow-up of 6.5 +/- 3.1 years, disability worsening occurred in 87 (26.2%) women. In the multivariable analysis, disability worsening was associated with pregnancy in women with relapses in the year before conception (adjusted hazard ratio (aHR) = 1.74; 95% confidence interval (CI) 1.06–2.84; p = 0.027), higher EDSS (aHR = 1.39; 95% CI 1.12–1.74; p = 0.003), younger age (aHR = 0.95; 95% CI 0.91–0.99; p = 0.022) and shorter DMD exposure over the follow-up (p < 0.008). Conclusion: Pregnancy in MS women with relapses in the year before conception increases the risk of long-term disability worsening. Our findings underscore the importance of counselling in MS women facing a pregnancy that should be planned after a period of clinical stability, favouring treatment optimization in patients with recent disease activity.

The Role of Perceived Job Exertion and Age as Moderators of the Relationship Between Gender and Upper Extremity Musculoskeletal Disability and Pain in Injured Workers.

Purpose This cross-sectional study aimed to determine if age and perceived job exertion (PJE) moderate the effect of gender on upper extremity (UE) disorders in injured workers. Methods We sampled a consecutive cohort of patients attending a specialty clinic for injured workers with UE musculoskeletal problems. We measured UE disability and pain using the Quick Disability of the Arm, Shoulder, and Hand (QDASH). Participants reported their PJE on a Global Rating of Change scale ranging from 1 (minimal perceived exertion) to 15 (maximal perceived exertion). Linear regression was used to explore the effect of gender on QDASH. We probed the moderating role of age and PJE using floodlight regression and identified the Johnson-Neyman (JN) region of age and PJE, where the effect of gender on QDASH becomes significant at the 95% level. Results We analyzed 418 participants, of whom 44% were women. The effect of gender on QDASH was significant for women aged 49 or younger (JN-region border: Age = 48.5, effect = 4.4, SE = 2.2, p = 0.05). Women workers with UE disorders younger than 49years old report higher levels of pain and disability than do men. After the age of 49years, both men and women workers experience a similar worsening of UE pain and disability with increasing age. Pain and disability increase with increased perceived job demands similarly for both men and women workers. Conclusions Women younger than 49years had higher levels of UE pain and disorders than men. Both men and women workers reported higher UE disability with an increase in their PJE.

Risk factors for venous thromboembolism and atherosclerotic cardiovascular disease: do they differ in patients with rheumatoid arthritis?

ObjectiveVenous thromboembolism (VTE) is an increasing concern in rheumatoid arthritis (RA) with little known about risk factors. We aimed to compare risk factors for unprovoked VTE and atherosclerotic cardiovascular disease...

Validity of a pre-surgical algorithm to predict pain, functional disability, and emotional functioning 1 year after spine surgery.

Psychopathology has been associated with patient reports of poor outcome and an algorithm has been useful in predicting short-term outcomes. The objective of this study is to investigate whether a pre-surgical psychological algorithm could predict 1-year spine surgery outcome reports, including pain, functional disability, and emotional functioning. A total of 1,099 patients consented to participate. All patients underwent spine surgery (e.g., spinal fusion, discectomy, etc.). Pre-operatively, patients completed self-report measures prior to surgery. An algorithm predicting patient prognosis based on data from the pre-surgical psychological evaluation was filled out by the provider for each patient prior to surgery. Post-operatively, patients completed self-report measures at 3- and 12-months after surgery. Longitudinal latent class growth analysis (LCGA) was used to derive patient outcome groups. These outcome groups were then compared to pre-surgical predictions made. LCGA analyses derived three groups of patients from the reported outcome data (entropy = .84): excellent outcomes, good outcomes, and poor outcomes. The excellent and good groups demonstrated improvements over time, but the poor outcome groups, on some measures, reported worsening of pain, functional disability, and emotional functioning over time. The pre-surgical algorithm yielded good concordance with the statistically derived outcome groups (Kendall's W = .81). Using a pre-surgical psychological evaluation algorithm for predicting long-term spine surgery outcomes can identify patients who are unlikely to report good outcomes, and point to areas for psychological intervention that can either improve surgery results or to be utilized as alternatives to elective spine surgery. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Network Damage Predicts Clinical Worsening in Multiple Sclerosis: A 6.4-Year Study.

ObjectiveIn multiple sclerosis (MS), clinical impairment is likely due to both structural damage and abnormal brain function. We assessed the added value of integrating structural and functional network MRI measures to predict 6.4-year MS clinical disability deterioration.MethodsBaseline 3D T1-weighted and resting-state functional MRI scans were obtained from 233 patients with MS and 77 healthy controls. Patients underwent a neurologic evaluation at baseline and at 6.4-year median follow-up (interquartile range = 5.06–7.51 years). At follow-up, patients were classified as clinically stable/worsened according to disability changes. In relapsing-remitting (RR) MS, secondary progressive (SP) MS conversion was evaluated. Global brain volumetry was obtained. Furthermore, independent component analysis identified the main functional connectivity (FC) and gray matter (GM) network patterns.ResultsAt follow-up, 105/233 (45%) patients were clinically worsened; 26/157 (16%) patients with RRMS evolved to SPMS. The treatment-adjusted random forest model identified normalized GM and brain volumes, decreased FC between default-mode networks, increased FC of the left precentral gyrus in the sensorimotor network (SMN), and GM atrophy in the fronto-parietal network (false discovery rate [FDR]-corrected p = range 0.01–0.09) as predictors of clinical worsening (out-of-bag [OOB] accuracy = 0.74). An expected contribution of baseline disability was also present (FDR-p = 0.01). Baseline disability, normalized GM volume, and GM atrophy in the SMN (FDR-p = range 0.01–0.09) were independently associated with SPMS conversion (OOB accuracy = 0.84). At receiver operating characteristic analysis, including network MRI variables improved disability worsening (p = 0.05) and SPMS conversion (p = 0.02) prediction.ConclusionsIntegration of MRI network measures helped determining the relative contributions of global/local GM damage and functional reorganization to clinical deterioration in MS.

Natalizumab in Early Relapsing-Remitting Multiple Sclerosis: A 4-Year, Open-Label Study.

IntroductionSTRIVE was a 4-year, multicenter, observational, open-label, single-arm study of natalizumab treatment in anti-JC virus antibody-negative (JCV-negative) relapsing-remitting multiple sclerosis (RRMS) patients with disease duration ≤ 3 years. The objective of STRIVE was to examine no evidence of disease activity (NEDA) status and predictors of NEDA in natalizumab-treated patients with early RRMS.MethodsProportions of patients with NEDA were evaluated along with baseline predictors of NEDA, annualized relapse rate, 24-week confirmed disability worsening (CDW), magnetic resonance imaging assessments (T2 and gadolinium-enhancing lesions), and serious adverse events.ResultsIn years 1 and 2, 56.1% (95% confidence interval [CI] 48.7–63.4%) and 73.6% (95% CI 66.2–80.2%) of patients (intent-to-treat population [N = 222]), respectively, achieved NEDA. In years 3 and 4, 84.6% (95% CI 78.0–89.9%) and 91.9% (95% CI 86.4–95.8%) of patients, respectively, achieved Clinical NEDA (no relapses or 24-week CDW). Baseline predictors of NEDA in year 4 were Expanded Disability Status Scale score ≤ 2.0 (odds ratio [OR] = 3.85 [95% CI 1.54–9.63]; p = 0.004) and T2 lesion volume > 4 cc (OR = 0.39 [95% CI 0.15–0.98]; p = 0.046), with the latter also predicting Clinical NEDA in year 4 (OR = 0.21 [95% CI 0.05–0.92]; p = 0.038). The cumulative probability of CDW at year 4 was 19.3%. Serious adverse events were reported in 11.3% of patients.ConclusionThese results support the long-term safety and effectiveness of natalizumab. Baseline predictors of NEDA help to inform benefit-risk assessments of natalizumab treatment in JCV-negative patients with early RRMS.Trial RegistrationClinicalTrials.gov identifier NCT01485003.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12325-021-01722-w.

POS1025 TOFACITINIB TREATMENT IN PATIENTS WITH PSORIATIC ARTHRITIS AND PROBABLE DEPRESSION AND/OR ANXIETY: A POST HOC ANALYSIS OF TWO PHASE 3 CLINICAL TRIALS

Background:Depression and anxiety are highly prevalent in patients (pts) with psoriatic arthritis (PsA),1 with inflammation a key pathogenic feature of depression in these pts.2 Tofacitinib is an oral Janus kinase inhibitor for the treatment of PsA. It acts by modulating immune and inflammatory responses. The link between major depressive disorder/generalised anxiety disorder (MDD/GAD), inflammation and tofacitinib effectiveness has not been fully explored.Objectives:Analyse the prevalence of probable MDD/GAD in pts with PsA initiating tofacitinib treatment and the impact of baseline (BL) probable MDD/GAD status on tofacitinib efficacy in these pts.Methods:This was a post hoc analysis of data from pts who received tofacitinib 5 or 10 mg twice daily (BID), or placebo (PBO), pooled from two Phase 3 trials (12-month OPAL Broaden [NCT01877668];3 6-month OPAL Beyond [NCT01882439]4). Pts with BL probable MDD and/or GAD were identified by a Short Form-36 Health Survey (SF-36) Mental Component Summary score (MCS) ≤38. Pt demographics/BL characteristics and outcomes were stratified by the presence (SF-36 MCS ≤38) or absence (SF-36 MCS &gt;38) of BL probable MDD/GAD. At Months (M)3/6/9/12, changes from BL in SF-36 MCS were evaluated, and efficacy assessed by the proportions of pts who achieved: Psoriatic Arthritis Disease Activity Score (PASDAS) ≤3.2, Health Assessment Questionnaire-Disability Index (HAQ-DI) improvement ≥0.35 and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) improvement ≥4. BL global pain was measured via visual analogue scale.Results:Of the 706 pts included in this analysis, BL probable MDD/GAD was identified in 46.2%, 44.9% and 46.2% of pts in the tofacitinib 5 mg BID (108/234), tofacitinib 10 mg BID (106/236) and PBO (109/236) groups, respectively. BL disease activity was similar across the three treatment groups, independent of probable MDD/GAD status (mean PASDAS: 6.1–6.4 in pts with vs 5.8–6.1 in pts without probable MDD/GAD). In the tofacitinib 5 mg BID group, mean BL scores for HAQ-DI (1.4 vs 1.0), FACIT-F total score (20.5 vs 32.4) and global pain (61.3 vs 51.5) indicated worse disability, fatigue and pain, respectively, for pts with vs without BL probable MDD/GAD. Similar findings were seen in the tofacitinib 10 mg BID and PBO groups. At M3, improvements from BL in SF-36 MCS in pts with probable MDD/GAD were numerically, but not significantly, greater with tofacitinib 5 and 10 mg BID vs PBO, and these changes were largely sustained to M12 (Figure 1a). At M3, numerically greater proportions of pts achieved improvements in PASDAS, HAQ-DI and FACIT-F with tofacitinib 5 or 10 mg BID vs PBO, regardless of BL probable MDD/GAD status (Figure 1b–d). Through M3–12, the proportions of pts who achieved PASDAS ≤3.2 with tofacitinib 5 or 10 mg BID were generally significantly greater in pts without vs with probable MDD/GAD (Figure 1b). At all timepoints, rates of improvement in HAQ-DI with tofacitinib 5 mg BID were numerically greater in pts with vs without probable MDD/GAD, whereas the opposite was true for tofacitinib 10 mg BID (Figure 1c). FACIT-F improvement rates with tofacitinib 10 mg BID were consistently numerically greater in pts with vs without probable MDD/GAD, while findings were mixed for tofacitinib 5 mg BID (Figure 1d).Conclusion:Around 46% of pts with PsA treated with tofacitinib had BL probable MDD/GAD (SF-36 MCS ≤38). Pts with BL probable MDD/GAD treated with tofacitinib had sustained changes in SF-36 MCS. Rates of clinical improvement with tofacitinib were generally greater in pts without vs with probable MDD/GAD, whereas findings for disability and fatigue improvements varied between tofacitinib doses. Further research is required to evaluate the relationship between PsA and depression, to improve treatment targets and the quality of life of pts with PsA.