Minimal Clinically Important Improvement Research Articles

Clinical cut-offs for hip- and knee arthroplasty outcome- minimal clinically important improvement (MCII) and patient acceptable symptom state (PASS) of patient-reported outcome measures (PROM).

Clinical cut-offs like minimum clinically important improvement (MCII) and patient acceptable symptom state (PASS) increase the interpretability of patient reported outcome measures (PROMs), but cut-off estimates vary considerably, clouding a clear definition of a successful surgical outcome. We report estimates of MCII and PASS following hip- and knee arthroplasty using multiple methods and compare the different estimation methods. Elective hip or knee arthroplasty patients who underwent the regular pre- and postoperative assessments 2014-2018 were included. The generic EQ-5D-5L and either the Hip or Knee disability/injury and Osteoarthritis Outcome Score (HOOS/KOOS) were used. MCII and PASS were estimated based on multiple estimation techniques. Distributions were skewed, with up to 95% being acceptable according to anchor questions. MCII estimates for HOOS/KOOS Pain ranged 21-60/10-47, with fewest in-sample misclassifications for the lowest cut-offs, provided by the 75th percentile approach. PASS estimates for HOOS/KOOS Pain ranged 84-93/78-91, for EQ-5D Index/EQ-VAS 0.87-0.92/66-79 (for hip), and 0.79-0.88/66-76 (for knee), with fewest misclassifications for the 75th percentile approach (hip) and Pythagoras approach (knee). The 75th percentile approach was the approach most often giving MCII estimates below the minimal detectable change (MDC). We report new one-year estimates of MCII and PASS of HOOS, KOOS and EQ-5D subscales following hip- and knee arthroplasty. Estimates varied considerably when using different anchors and estimation techniques. Overall, the 75th percentile approach had fewest misclassifications, and had the lowest thresholds for the MCII estimations, but which were often below the MDC.

Early Improvements with Guselkumab Associate with Sustained Control of Psoriatic Arthritis: Post hoc Analyses of Two Phase 3 Trials.

Patterns of treatment response can inform clinical decision-making. This study assessed the course and impact of achieving minimal clinically important improvement (MCII) in clinical measures and patient-reported outcomes (PROs) with guselkumab in patients with active psoriatic arthritis (PsA). Post hoc analyses evaluated 1120 patients with PsA receiving guselkumab every 4or8weeks (Q4W/Q8W) or placebo from DISCOVER-1 (31% tumor necrosis factor inhibitor-experienced) and DISCOVER-2 (biologic-naïve). Achievement of MCII in clinical Disease Activity Index for PsA (cDAPSA), patient global assessment (PtGA) of arthritis, PtGA of psoriasis, patient-reported pain, Functional Assessment of Chronic Illness Therapy-Fatigue, Health Assessment Questionnaire-Disability Index, 36-item Short-Form Health Survey Physical Component Summary score, PtGA Arthritis + Psoriasis, and PsA Disease Activity Score (PASDAS) was compared between the guselkumab and placebo groups using Cox regression. Logistic regression adjusting for baseline factors evaluated associations between early (W4/W8) MCII achievement and stringent response (≥%50/%70 improvement in American College of Rheumatology response criteria, cDAPSA low disease activity [LDA], PASDAS LDA, and minimal disease activity) at W24/W52 among guselkumab-randomized patients. Among patients with highly active PsA (baseline cDAPSA = 44.1-45.0, PASDAS = 6.4-6.5), times to MCII were significantly faster for guselkumab vs. placebo (hazard ratios 1.3-2.5; P < 0.05). Across measures, at first timepoint assessed, MCII rates were significantly higher with guselkumab (Q4W/Q8W 28-68%/29-65%) vs. placebo (19-47%; both P < 0.05). Early (W4/W8) MCII with guselkumab associated with higher odds of achieving stringent responses at W24/W52 (odds ratios 1.4-17.2/1.4-5.4). In a mixed PsA population, significant proportions of patients treated with guselkumab achieved early (W4/W8) MCII across clinical and PRO measures, which associated with ahigher likelihood of attaining clinically relevant improvements and low levels of disease activity at W24/W52. DISCOVER-1 (NCT03162796). DISCOVER-2 (NCT03158285).

The impact of diabetes on physical and mental health status and patient satisfaction after total hip and knee arthroplasty.

To assess the impact of diabetes on physical and mental health status, as well as patient satisfaction, one-year following knee and hip total joint arthroplasty (TJA) for osteoarthritis (OA). Participants were 626 hip and 754 knee TJA patients. Pre-surgery data were collected on socio-demographics and health status. The 12-item Short Form Health Survey (SF-12) was collected pre- and one year post-surgery, and physical (PCS) and mental component (MCS) summary scores computed. One-year patient satisfaction was also recorded. Four regression models tested the effect of diabetes on: 1) PCS change score; 2) MCS change score; 3) achieving minimal clinically important improvement (MCII) on PCS; and 4) patient satisfaction ('Somewhat or Very Satisfied' vs. 'Somewhat or Very Dissatisfied'). An interaction between surgical joint and diabetes was tested in each model. Self-reported diabetes prevalence was 13.0% (95% CI: 11.2%-14.7%) and was more common in knee 16.1% (95% CI: 13.4%-18.7%) than hip 9.3% (95% CI: 7.0%-11.5%) patients. In adjusted analyses, change scores were 2.3 units less on the PCS for those with diabetes compared to those without (p = 0.005). Patients with diabetes were about half as likely to achieve MCII as patients without diabetes (p = 0.004). Diabetes was not significantly associated with satisfaction or changes in MCS scores. Diabetes effects did not differ by surgical joint. Findings support that diabetes has a negative impact on improvements in physical health after TJA. Considering the growing prevalence of OA and diabetes in the population, our findings support the importance of perioperative screening and management of diabetes in patients undergoing TJA.

Women show a positive response to platelet-rich plasma despite presenting more painful knee osteoarthritis than men.

The purpose of this study was to evaluate the impact of gender on the efficacy of platelet-rich plasma (PRP) in patients with knee osteoarthritis (KOA), comparing their short-term response between men and women. Four hundred-eighteen patients (529 knees) were included. Patients were treated with threeinjections of PRP on a weekly basis. Blood and PRP samples were randomly tested. Patients were asked to complete the knee injury and osteoarthritis outcome score (KOOS) and 12-item short form survey (SF-12), at baseline and 6 months. Success rates were calculated according to a reduction in the pain score of at least 9.3 points [minimal clinically important improvement (MCII)]. Comparative tests and multivariate regression were performed. The PRP had a platelet concentration factor of 2.0X compared to blood levels, with no leucocytes or erythrocytes. KOOS scores showed an increase from baseline to 6 months (p < 0.0001). There was an increase in the physical component summary (PCS) (p < 0.0001) and mental component summary (MCS) (p < 0.01) of the SF-12. The number of knees of women with MCII was 156 out of 262 (59.6%), whereas the number of knees of men was 136 out of 267 (50.9%) (p = 0.0468). Women had worse baseline scores on pain (p = 0.009), PCS (p < 0.0001) and MCS (p < 0.0001). Although the symptomatology generated by KOA was worse in women when compared to men, treatment with repeated injections of PRP was effective, ultimately achieving a higher improvement in women providing comparable final follow-up outcomes between men and women. Level IV.

High survival rate after the combination of intrameniscal and intraarticular infiltrations of platelet-rich plasma as conservative treatment for meniscal lesions.

To evaluate the efficacy of applying a combination of intrameniscal and intraarticular infiltrations of Platelet-Rich Plasma (PRP) in patients with meniscal tears, analyzing its failure rate and clinical evolution, as well as factors that may influence the positive response to this treatment. Three hundred and ninety-two cases out of 696 met the inclusion criteria and were included in this work. Survival and patient-reported outcome measure (PROM) were collected and analyzed. Survival rate was defined as the percentage of patients who did not undergo meniscus surgery during their follow-up time. Patients were asked to complete the Knee injury and Osteoarthritis Outcome Score (KOOS) at baseline, 6months and 18months. Other patient- and pathology-related variables were collected. Blood and PRP samples were randomly tested as a quality control measure. Survival and comparative statistical tests, and multivariate regression were performed for the analysis of the variables. The PRP applied had a platelet concentration factor of 1.9X in respect to blood levels, with no leukocytes or erythrocytes. Thirty-eight patients required surgical intervention after treatment reaching a survival rate of 90.3% with an estimated mean survival time of 54.4months. The type of injury (P = 0.002) and the presence of chondropathy were risk factors for surgical intervention after PRP treatment (P = 0.043). All KOOS scores showed a significant statistical increase from baseline to 6months (N = 93) and 18months (N = 66) (P < 0.0001). The number of cases with minimal clinically important improvement (MCII) at 6months and 18months post-treatment was 65 (69.9%) and 43 (65.2%), respectively. The combination of intrameniscal and intraarticular PRP infiltrations is a valid conservative treatment for meniscal injuries avoiding the need for surgical intervention. Its efficacy is higher in horizontal tears and decreases when joint degeneration is present. Level IV.

Efficacy and safety of curcumin in patients with metabolic phenotype of osteoarthritis: A pilot study

The aim of this study was to assess efficacy and safety of curcumin in metabolic syndrome- associated osteoarthritis (MetS-OA). All patients provided written informed consent. Knee OA was diagnosed according to American College of Rheumatology criteria; MetS was diagnosed according to Russian Scientific Society of Cardiology Guidelines. The study had before-and-after design. The main inclusion criteria were presence of knee OA and MetS, levels of global health assessment and pain assessment more than 50 mm using 0-100 visual analogue scale (VAS). The main outcome was VAS global. The other outcomes were VAS pain, Knee injury and Osteoarthritis Outcome Score (KOOS) consisting of five subscales: pain (KOOS pain), other symptoms (KOOS symptoms), activities in daily living (KOOS ADL), function in sport and recreation (KOOS Sport/Rec) and knee related Quality of life (KOOS QoL). The level of depression was measured using PHQ- 9. For pain, proportion of patients achieving minimal clinically important improvement (MCII) was assessed using the cut-offs of (a) 15 of 100 for absolute improvement and 20% for relative improvement.The treatment consisted of C. longa extract 1000 mg/day for 4 weeks. The assessments were performed on baseline and 4 weeks thereafter. Eighteen women with MetS-OA of the knee were included in the study.At the end of treatment, there were significant improvements in the VAS global scale by an average 33.9 mm (p = 0.001), VAS pain by 25 mm (p = 0.001). There was a trend towards improvement in PHQ-9 by 2.9 (p = 0.05). The mean improvement in KOOS pain was 11 (p = 0.001). KOOS symptoms improved by 9 (p = 0.025), KOOS ADL - by 12.4 (p = 0.001), KOOS Sport/Rec by 10.3 (p = 0.044), and KOOS QOL by 14.4 (p = 0.009). The proportion of patients achieving clinically significant improvement (MCII) were nine (56%) for both global health and pain. There were no adverse events during the study. The findings of this study suggest clinical efficacy and safety of C. Longa in MetS-associated knee OA. There is a need for large controlled studies to confirm these results.

Responsiveness and Minimum Clinically Important Difference in Patient-Reported Outcome Measures Among Patients With Psoriatic Arthritis: A Prospective Cohort Study.

To determine the responsiveness to therapy and minimum clinically important improvement (MCII) for patient-reported outcome measures in psoriatic arthritis (PsA) and to examine the impact of baseline disease activity on the ability to demonstrate change. A longitudinal cohort study was performed within the PsA Research Consortium. Patients completed several patient-reported outcomes, including the Routine Assessment of Patient Index Data, the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), the Psoriatic Arthritis Impact of Disease 12-item (PsAID12) questionnaire, and others. The mean change in the scores between visits and standardized response means (SRMs) were calculated. The MCII was calculated as the mean change in score among patients who reported minimal improvement. SRMs and MCIIs were compared among subgroups with moderate to highly active PsA and those with lower disease activity. Among 171 patients, 266 therapy courses were included. The mean ± SD age was 51 ± 13.8 years, 53% were female, and the mean swollen and tender joint counts were 3 and 6, respectively, at baseline. SRMs and MCII for all measures were small to moderate, although greater among those with higher baseline disease activity. BASDAI had the best SRM overall and for less active PsA, and the clinical Disease Activity of PsA (cDAPSA) and PsAID12 were best for those with higher disease activity. SRMs and MCII were relatively small in this real-world population, particularly among those with lower disease activity at baseline. BASDAI, cDAPSA, and PsAID12 had good sensitivity to change, but selection for use in trials should consider the baseline disease activity of patients to be enrolled.

Development and testing of an alternative responder definition for EULAR Sjögren’s Syndrome Patient Reported Index (ESSPRI)

ObjectivesDryness, fatigue and joint/muscle pain are typically assessed in Sjögren’s trials using European Alliance of Associations for Rheumatology Sjögren’s Syndrome Patient Reported Index (ESSPRI). A Patient Acceptable Symptom State of...

A multi-center, open-label, randomized study to explore efficacy and safety of baricitinib in active primary Sjogren’s syndrome patients

BackgroundPrimary Sjogren’s syndrome (pSS) is a systemic autoimmune disease involving multiple organ systems. The Janus kinase/signal transduction and activator of transcription (JAK/STAT) signaling pathway is a key pathway involving the pathogenesis of pSS. Baricitinib, a selective JAK1 and JAK2 inhibitor, has been approved for treatment of active rheumatoid arthritis and reported in treatment of some other autoimmune diseases including systemic lupus erythematosus. We have found that baricitinib might be effective and safe in pSS in a pilot study. However, there is no published clinical evidence of baricitinib in pSS. Hence, we conducted this randomized study to further explore the efficacy and safety of baricitinib in pSS.MethodsThis is a multi-center, prospective, open-label, randomized study to compare the efficacy of baricitinib + hydroxychloroquine (HCQ) with HCQ alone in pSS patients. We plan to involve 87 active pSS patients with European League Against Rheumatism pSS disease activity index (ESSDAI) ≥ 5 from eight different tertiary centers in China. Patients will be randomized (2:1) to receive baricitinib 4 mg per day + HCQ 400 mg per day or HCQ 400 mg per day alone. We will switch HCQ to baricitinib + HCQ if the patient in the latter group has no ESSDAI response at week 12. The final evaluation will be at week 24. The primary endpoint is the percentage of ESSDAI response, or minimal clinically important improvement (MCII), which was defined as an improvement of ESSDAI at least three points at week 12. The secondary endpoints include EULAR pSS patient-reported index (ESSPRI) response, change of Physician’s Global Assessment (PGA) score, serological activity parameters, salivary gland function test, and focus score on labial salivary gland biopsy.DiscussionThis is the first randomized controlled study to evaluate the clinical efficacy and safety of baricitinib in pSS. We hope that the result of this study can provide more reliable evidence of the efficacy and safety of baricitinib in pSS.Trial registrationClinicalTrials.gov NCT05016297. Registered on 19 Aug 2021.

Qualitative Research with Patients and Physicians to Assess Content Validity and Meaningful Change on ESSDAI and ESSPRI in Sjögren's.

IntroductionEuropean Alliance of Associations for Rheumatology (EULAR) Sjögren’s Syndrome Disease Activity Index (ESSDAI) is a clinician-reported outcome (ClinRO) instrument, assessing Sjögren’s disease activity from the physician perspective. EULAR Sjögren’s Syndrome Patient Reported Index (ESSPRI) is a patient-reported outcome (PRO) instrument, assessing patient-defined Sjögren’s symptom severity. Both instruments are commonly used as clinical trial endpoints and have been psychometrically validated. However, qualitative evidence supporting content validity and what constitutes a meaningful change is limited. Qualitative evidence supporting Physician/Patient Global Assessment of disease activity and symptom severity (PhGA/PaGA) items used within anchor-based analyses for ESSDAI/ESSPRI is also lacking.MethodsQualitative, semi-structured, telephone/video interviews were conducted with patients with Sjögren’s (n = 12) and physicians who specialise in Sjögren’s (n = 10). Interviews explored: appropriateness of ESSDAI domain weights and meaningful improvements on domain/total scores from the physician perspective, appropriateness of ESSPRI’s 2-week recall period from the patient/physician perspective, patients’ perspectives on meaningful improvements in ESSPRI total scores, and patients’/physicians’ interpretation of PhGA/PaGA items.ResultsMost ESSDAI domain weights were considered clinically appropriate. Generally, a one-category improvement in domain-level scores and a 3-point improvement in total ESSDAI scores were considered clinically meaningful. Most patients/physicians considered ESSPRI’s 2-week recall period appropriate, and patients considered a 1-to-2-point ESSPRI total score improvement meaningful. PhGA/PaGA items developed for use as ESSDAI/ESSPRI anchors were consistently interpreted.ConclusionsThe findings support use of ESSDAI and ESSPRI as Sjögren’s clinical trials endpoints, as well as in clinical practice and other research settings. Qualitative data exploring meaningful change supports existing minimal clinically important improvement (MCII) thresholds.

Responder Analysis of Pain Relief After Surgery for the Treatment of Spinal Metastatic Tumors.

Central tendency analysis studies demonstrate that surgery provides pain relief in spinal metastatic tumors. However, they preclude patient-specific probability of treatment outcome. To use responder analysis to study the variability of pain improvement. In this single-center, retrospective analysis, 174 patients were studied. Logistic regression modeling was used to associate preoperative characteristics with rating the Brief Pain Inventory (BPI) worst pain item 0 to 4. Linear regression modeling was used to associate preoperative characteristics with minimal clinically important improvement (MCI) in physical functioning defined by a 1-point decrease in the BPI Interference Construct score from preoperative baseline to 6 months postoperatively. Patient-level analysis revealed that 60% of patients experienced an improvement in pain. At least half experienced a decrease in pain resulting in MCI in physical functioning. Cutpoint analysis revealed that 48% were responders. Increasing scores on the preoperative pain intensity BPI items, the MD Anderson Symptom Inventory (MDASI) Core Symptom Severity Construct, the MDASI Spine Tumor-Specific Construct, the presence of preoperative neurologic deficits, and postoperative complications were associated with lower probability of treatment success while increasing severity in all BPI pain items, and MDASI constructs were associated with increased probability of MCI in physical function. Significant mortality and loss to follow-up intrinsic to this patient population limit the strength of these data. Although patients with milder preoperative symptoms are likely to achieve better pain relief after surgery, patients with worse preoperative symptom also benefit from surgery with adequate pain relief with an improvement in physical function.

Establishment of Minimal Clinically Important Improvement for Patient-Reported Symptoms to Define Recovery After Video-Assisted Thoracoscopic Surgery.

The aim of this study was to define a threshold of minimal clinically important improvement (MCII) for interpreting patient condition following video-assisted thoracoscopic surgery (VATS). Patients undergoing VATS were recruited for this multicenter, prospective, observational cohort study. Symptoms were measured using the MD Anderson Symptom Inventory-Lung Cancer Module perioperatively. To define MCIIs, we first identified index symptoms, defined as the most severe symptoms showing the largest reduction from day 1 post-surgery to discharge. MCIIs for each index symptom were then obtained via an anchor-based approach. Symptom recovery was defined as an MCII after post-surgery day 1. Cox regression models were used to identify risk factors for unrecovered index symptoms. Using 366 patients, we identified pain and fatigue as index symptoms after VATS. MCII was defined as a 30% reduction in pain or fatigue. At discharge, 22.6% of patients had not recovered from pain and 22.4% had not recovered from fatigue. Cox models found that risk factors for unrecovered pain were Charlson Comorbidity Index score ≥1 (hazard ratio [HR] 1.36, 95% confidence interval [CI] 1.04-1.77; p=0.02) and preoperative neoadjuvant therapy (HR 2.78, 95% CI 1.13-6.83; p=0.02). Malignancy was a risk factor for unrecovered fatigue (HR 1.47, 95% CI 1.02-2.13; p=0.04). Pain and fatigue can be used as index measures for symptom recovery in patients following VATS. A 30% MCII represented meaningful recovery after VATS and could identify patients who may need extensive care after discharge.

Periosteal Needling to the Cervical Articular Pillars as an Adjunct Intervention for Treatment of Chronic Neck Pain and Headache: A Case Report

(1) Background: Periosteal dry needling (PDN) involves clinicians using a solid filiform needle to stimulate bone for analgesic purposes. This case report presents the use of PDN to the cervical articular pillars (CAPs) in an 85-year-old female with chronic neck pain and headache. (2) Case description: PDN was applied to the right C2–C3 articular pillars, following trigger point dry needling (TrPDN) and manual therapy, in order to provide a direct sensory stimulus to the corresponding sclerotomes. PDN added over two treatments led to improved cervical range of motion and eliminated the patient’s neck pain and headache at 1 week follow-up. (3) Outcomes: At discharge, clinically relevant improvements were demonstrated on the numeric pain rating scale (NPRS), which improved from an 8/10 on intake to a 0/10 at rest and with all movements. In addition, the patient exceeded the risk adjusted predicted four-point score improvement and the minimal clinically important improvement (MCII) value of four points on the Focus on Therapeutic Outcomes (FOTO) Neck Functional Status (Neck FS). At one month post-discharge, the patient remained symptom-free. (4) Discussion: In the context of an evidence-informed approach for neck pain and headache, PDN led to marked improvements in pain and function. Patient outcomes exceeded predictive analytic expectations for functional gains and efficient utilization of visits and time in days. Combined with other interventions, PDN to the CAPs could be a viable technique to treat chronic neck pain with headache.

Real-world evidence to assess the effectiveness of platelet-rich plasma in the treatment of knee degenerative pathology: a prospective observational study.

Objective:The present work aims to analyse the effectiveness of platelet-rich plasma (PRP) in degenerative knee pathology based on real-world data and to evaluate possible factors influencing the response to treatment.Methods:In total, 531 cases were analysed collecting data on gender, age, body mass index, pathology location, severity, number of cycles and route of administration. Clinical outcome was evaluated at 6 and 15 months after treatment, using the Knee injury and Osteoarthritis Outcome Score (KOOS) and obtaining percentages of Minimal Clinically Important Improvement (MCII). Blood and PRP samples were randomly tested as a quality control measure to ensure the correct properties. Comparative statistical tests and multivariate regression were performed for the analysis of the variables.Results:The PRP applied had a platelet concentration factor of 1.67, with no leukocytes or erythrocytes. The percentage of patients with MCII at 6 and 15 months after PRP application was 59.32% and 70.62%, respectively. Patients with MCII were younger (p = 0.0246) and with lower body mass index (p = 0.0450). The treatment had a better response in mild/moderate cases than in severe cases (p = 0.0002). Intraosseous PRP application in severe cases improved the effect of intraarticular PRP (p = 0.0358). The application of a second cycle of PRP only improved the response in patients without MCII at 6 months (p = 0.0029), especially in mild/moderate cases (p = 0.0357).Conclusion:The applications of PRP in degenerative knee pathologies is an effective treatment, but this effectiveness nonetheless depends on several variables. Real-world data can complement that from clinical trials to provide valuable information.

Single and Composite Endpoints of Within-Patient Improvement in Symptoms: Pooled Tanezumab Data in Patients with Osteoarthritis.

IntroductionCombining measures of key core domains (especially pain and function) into a composite endpoint that requires each patient to meet a threshold of improvement for each domain provides information on multiple aspects of osteoarthritis within individual patients. This pooled analysis of two phase 3 studies (NCT02697773, NCT02709486) explored single and composite endpoints for assessing within-patient improvement in knee or hip osteoarthritis symptoms following subcutaneous administration of tanezumab or placebo.MethodsEndpoints at week 16 included proportions of responders (≥ 30% improvement) in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain, WOMAC Physical Function, WOMAC Pain/Function composite, and weekly average pain; and patient acceptable symptom state (PASS) composite responders, minimal clinically important improvement (MCII) composite responders, Outcome Measures in Rheumatology-Osteoarthritis Research Society International (OMERACT-OARSI) responders, and sustained weekly average pain responders.ResultsPooled population comprised 1545 patients. Of patients who had a ≥ 30% improvement in WOMAC Pain and/or WOMAC Physical Function, 88.5% were WOMAC Pain/Function composite responders, 7.0% were WOMAC Pain (but not Function) responders, and 4.4% were WOMAC Function (but not Pain) responders. Of weekly average pain responders, 43.1% were PASS composite responders. Odds ratios (tanezumab 2.5 mg and 5 mg groups, respectively, vs placebo) were 1.75 and 1.86 (WOMAC Pain/Function composite responders), 1.41 and 1.65 (weekly average pain responders), 1.60 and 1.73 (PASS composite responders), 1.52 and 1.68 (MCII composite responders), 1.75 and 1.88 (OMERACT-OARSI responders), and 1.85 and 1.48 (sustained weekly average pain responders). Subgroup analyses suggested a greater magnitude of effect for patients with a knee index joint compared with hip on some endpoints.ConclusionResponders on single pain endpoints were in many cases also responders on function or composite endpoints. Separation of tanezumab from placebo was similar and consistent across single and composite endpoints.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40744-021-00372-2.

Gut microbial determinants of clinically important improvement in patients with rheumatoid arthritis

BackgroundRapid advances in the past decade have shown that dysbiosis of the gut microbiome is a key hallmark of rheumatoid arthritis (RA). Yet, the relationship between the gut microbiome and clinical improvement in RA disease activity remains unclear. In this study, we explored the gut microbiome of patients with RA to identify features that are associated with, as well as predictive of, minimum clinically important improvement (MCII) in disease activity.MethodsWe conducted a retrospective, observational cohort study on patients diagnosed with RA between 1988 and 2014. Whole metagenome shotgun sequencing was performed on 64 stool samples, which were collected from 32 patients with RA at two separate time-points approximately 6–12 months apart. The Clinical Disease Activity Index (CDAI) of each patient was measured at both time-points to assess achievement of MCII; depending on this clinical status, patients were distinguished into two groups: MCII+ (who achieved MCII; n = 12) and MCII− (who did not achieve MCII; n = 20). Multiple linear regression models were used to identify microbial taxa and biochemical pathways associated with MCII while controlling for potentially confounding factors. Lastly, a deep-learning neural network was trained upon gut microbiome, clinical, and demographic data at baseline to classify patients according to MCII status, thereby enabling the prediction of whether a patient will achieve MCII at follow-up.ResultsWe found age to be the largest determinant of the overall compositional variance in the gut microbiome (R2 = 7.7%, P = 0.001, PERMANOVA). Interestingly, the next factor identified to explain the most variance in the gut microbiome was MCII status (R2 = 3.8%, P = 0.005). Additionally, by looking at patients’ baseline gut microbiome profiles, we observed significantly different microbiome traits between patients who eventually showed MCII and those who did not. Taxonomic features include alpha- and beta-diversity measures, as well as several microbial taxa, such as Coprococcus, Bilophila sp. 4_1_30, and Eubacterium sp. 3_1_31. Notably, patients who achieved clinical improvement had higher alpha-diversity in their gut microbiomes at both baseline and follow-up visits. Functional profiling identified fifteen biochemical pathways, most of which were involved in the biosynthesis of L-arginine, L-methionine, and tetrahydrofolate, to be differentially abundant between the MCII patient groups. Moreover, MCII+ and MCII− groups showed significantly different fold-changes (from baseline to follow-up) in eight microbial taxa and in seven biochemical pathways. These results could suggest that, depending on the clinical course, gut microbiomes not only start at different ecological states, but also are on separate trajectories. Finally, the neural network proved to be highly effective in predicting which patients will achieve MCII (balanced accuracy = 90.0%, leave-one-out cross-validation), demonstrating potential clinical utility of gut microbiome profiles.ConclusionsOur findings confirm the presence of taxonomic and functional signatures of the gut microbiome associated with MCII in RA patients. Ultimately, modifying the gut microbiome to enhance clinical outcome may hold promise as a future treatment for RA.

Defining Minimum Clinically Important Changes for the Patient Activity Scale II.

To define the minimum clinically important improvement (MCII) and minimum clinically important worsening (MCIW) for the Patient Activity Scale II (PAS-II; range 0-10), a recommended patient-reported outcome measuring rheumatoid arthritis disease activity. Data were taken from Forward, The National Databank for Rheumatic Diseases, from four 6-month data collection periods. Both anchor-based and distribution-based methods were used to estimate the MCII and MCIW. Anchor-based analyses used comparisons of pain and general health to the previous 6 months. Distribution-based analyses used 0.5 and 0.35 SDs. We stratified analyses based on the PAS-II score (above/below 3.7), hypothesizing that the MCII and MCIW would depend on the baseline score. To assess construct validity, we evaluated the odds of achieving the MCII in patients receiving new therapies. In the overall sample, for pain and general health anchor questions, the MCIW was 0.50 and 0.55, respectively. The MCII was defined as 0.39 and 0.45, respectively, for pain and general health. The MCIW for anchor-based methods among participants with low disease activity was 1.10 (1.09/1.11 [pain/general health]), while the MCII for those with moderate-to-high disease activity was 1.09 (1.15/1.02 [pain/general health]). Distribution-based methods for 0.5 and 0.35 SD were 1.08 and 0.76, respectively, for pain and general health. There was fair-to-excellent agreement with clinically important differences in assessments of pain and disability. Patients receiving new treatments had 30% greater odds of achieving the MCII. The minimum important change in PAS-II score was approximately 0.5. Among participants with a moderate-to-high PAS-II score , the MCII was 1.1, and among participants with low disease activity, the MCIW was 1.1.

One-Year, Efficacy and Safety Open Label Study, with a Single Injection of a New Hyaluronan for Knee OA: The SOYA Trial.

PurposeTo assess the efficacy and safety of a single injection of a new formulation of hyaluronic acid (MPS-HA2%) in patients with symptomatic knee osteoarthritis after 12 months’ follow-up.Patients and MethodsProspective, single-arm, multicentre, open-label, 12-month follow-up study. Patients with Kellgren–Lawrence (KL) 2–3 and visual analogue scale (VAS) pain scores of ≥40–< 80 mm received a single injection of MPS-HA2%. The primary outcome was the reduction in VAS pain scores from baseline, and the secondary outcomes were the Western Ontario and McMaster (WOMAC) Universities Osteoarthritis Index, the minimum clinically important improvement (MCII), and patient and investigator global assessments (PGA, IGA) measured on 5-point Likert scale. Adverse events were recorded throughout the study for safety purposes.ResultsA total of 101 patients (mean age: 68 years; 74% female; and 78% overweight) were included. The mean reduction in pain at 12 months was 37.7%; the total WOMAC score improved by 36.5% and the pain, stiffness and physical function subscores returned improvements of 32.1%, 34.1% and 32.7%, respectively (p=0.0001 with respect to baseline). At 12 months, a statistically significant 62.2% of patients obtained an improvement equal to or greater than the MCII. The mean PGA score at baseline was 2.44 and 1.46 at 12 months (p<0.05), and the mean IGA scores at equivalent timepoints were 2.29 and 1.48 (p<0.05). Fourteen patients received a second injection at the 6-month follow-up visit. Eight patients reported a total of 12 treatment-related adverse events that were local, non-serious and of mild-to-moderate intensity.ConclusionWith just a single intra-articular injection, this not controlled trial suggests that MPS-HA2% is effective 12 months after the procedure in most cases. Patient tolerability and safety were both optimal (NCT03852914).

Preoperative ASES Scores Can Predict Substantial Clinical Benefit at 2 Years Following Total Shoulder Arthroplasty.

Preoperative patient-reported outcome measures (PROMs) have been shown to influence outcomes after total shoulder arthroplasty (TSA), although little is known about this relationship. An institutional shoulder arthroplasty registry was retrospectively queried for preoperative and 2-year postoperative 12-Item Short Form Health Survey (SF-12) and American Shoulder and Elbow Surgeons (ASES) scores for patients who underwent anatomic TSA (aTSA) or reverse TSA (rTSA). Preoperative PROMs were evaluated for their effect on patient achievement of minimal clinically important improvement (MCII) and substantial clinical benefit (SCB). In total, 451 aTSA patients and 93 rTSA patients had preoperative and 2-year follow-up scores. A total of 91.7% and 70.4% of patients achieved MCII and SCB at 2 years, respectively (P<.001). Preoperative ASES scores were more predictive of achieving SCB than MCII (area under the curve [AUC], 0.83 vs 0.71). When accounting for mental and emotional health, the predictive ability of SF-12 physical component threshold values improved (AUC, 0.68). Preoperative threshold PROMs were found to accurately predict achievement of clinically significant outcomes at 2 years. Considering mental and emotional health improved the accuracy of these predictions. These data will assist surgeons and patients alike in setting expectations for outcomes after TSA. [Orthopedics. 2021;44(4):e509-e514.].

Clusters of Responders and Predictive Factors for Response to Supplementation with Boswellia, Turmeric, and Red Algae Extracts in Painful Knee Osteoarthritis: A Prospective Observational Study Using an Arsenal of Patient-Centered Measures.

PurposeThis observational study evaluated a combination of boswellia, turmeric, and red algae extracts in patients with knee osteoarthritis (KOA). Given the growing interest in patient-centered care in osteoarthritis, effects were assessed by an arsenal of patient-reported outcome measures (PROMs): Patient Acceptable Symptom Scale (PASS), Minimal Clinically Important Improvement (MCII), Patient Global Impression of Change (PGIC), and Lequesne algofunctional index (LAFI). Patients also completed a list of 17 items on pain quality.Patients and MethodsPatients with painful unilateral or bilateral KOA had to take 1–4 capsules per day of a dietary supplement containing boswellia, turmeric, and red algae extracts for 90 days. Patients completed PROMs on Days 0 (baseline), 10, 20, 30, 60, and/or 90.ResultsA total of 118 patients [female: 69.5%; age: 62.9 (9.5) years, mean (SD)] were included in the study and took at least one capsule. Mean (SD) follow-up duration was 100.7 (54.9) days. Pain relief was maximal on Day 90: 64.5% of patients were responders (positive PASS); 68.8% and 58.4% had MCII and PGIC scores indicating positive effect (score ≥3) or global improvement (score ≥5); 73.3% (versus 47.5% at baseline) were mildly/moderately disabled (LAFI score <8); 55.2% had meaningful decrease (−30%) in pain intensity (VAS), 35.1% (versus 59.2% at baseline) took analgesics as supplementary treatment. Median time to the first PASS change was 34 days. Pain intensity (VAS), as well as two pain characteristics (ie, “Stabbing pain” and “Widespread pain”), were independent factors associated with non-response on Day 30. Four clusters of responders were isolated according to pain characteristics, with one cluster exhibiting a higher responder rate.ConclusionThe results of this preliminary study suggest that the combination of boswellia, turmeric, and red algae extracts tested could improve KOA patients. Beyond these results, this study showed the importance of PROMs and specific pain qualitative descriptors for the accurate evaluation of dietary supplement approaches in painful conditions.