Meaningful Improvements In Pain Research Articles

Smallest Clinically Meaningful Improvement in Amputation-Related Pain and Brief Pain Inventory Scores as Defined by Patient Reports of Global Improvement After Cryoneurolysis: a Retrospective Analysis of a Randomized, Controlled Clinical Trial.

The smallest meaningful improvement in pain scores (minimal clinically important difference [MCID]) after an analgesic intervention is essential information when both interpreting published data and designing a clinical trial. However, limited information is available for patients with chronic pain conditions, and what is published is derived from studies involving pharmacologic and psychological interventions. We here calculate these values based on data collected from 144 participants of a previously published multicenter clinical trial investigating the effects of a single treatment with percutaneous cryoneurolysis. In the original trial, we enrolled patients with a lower-limb amputation and established phantom pain. Each received a single-injection femoral and sciatic nerve block with lidocaine and was subsequently randomized to receive either ultrasound-guided percutaneous cryoneurolysis or sham treatment at these same locations. Investigators, participants, and clinical staff were masked to treatment group assignment with the exception of the treating physician performing the cryoneurolysis, who had no subsequent participant interaction. At both baseline and 4 months (primary end point), participants rated their phantom limb pain based on a numeric rating scale (NRS) and their interference of pain on physical and emotional functioning as measured with the Brief Pain Inventory's interference subscale. They subsequently qualitatively defined the change using the 7-point ordinal Patient Global Impression of Change (PGIC). The smallest clinically meaningful improvements in phantom limb pain and Brief Pain Inventory scores were calculated using an anchor-based method based on the PGIC. The median (interquartile range [IQR]) phantom pain NRS (0-10) improvements at 4 months considered small, medium, and large were 1 [1-1], 3 [3-4], and 4 [3-6], respectively. The median improvements in the Brief Pain Inventory interference subscale (0-70) associated with a small, medium, and large analgesic changes were 16 [6-18], 24 [22-31], and 34 [22-46]. The proportions of patients that experienced PGIC ≥5 were 33% and 36% in the active and placebo groups, respectively. The relative risk of a patient experiencing PGIC ≥5 in the active group compared to the sham group with 95% confidence interval was 0.9 (0.6-1.4), P = .667. Amputees with phantom limb pain treated with percutaneous cryoneurolysis rate analgesic improvements as clinically meaningful similar to pharmacologic treatments, although their MCID for the Brief Pain Inventory was somewhat larger than previously published values. This information on patient-defined clinically meaningful improvements will facilitate interpretation of available studies and guide future trial design.

ReNeu: A Pivotal, Phase IIb Trial of Mirdametinib in Adults and Children With Symptomatic Neurofibromatosis Type 1-Associated Plexiform Neurofibroma.

Pharmacologic therapies for neurofibromatosis type 1-associated plexiform neurofibromas (NF1-PNs) are limited; currently, none are US Food and Drug Administration-approved for adults. ReNeu is an open-label, multicenter, pivotal, phase IIb trial of mirdametinib in 58 adults (≥18 years of age) and 56 children (2 to 17 years of age) with NF1-PN causing significant morbidities. Patients received mirdametinib capsules or tablets for oral suspension (2 mg/m2 twice daily, maximum 4 mg twice daily), regardless of food intake, in 3 weeks on/1 week off 28-day cycles. The primary end point was confirmed objective response rate (ORR; proportion of patients with a ≥20% reduction of target PN volume from baseline on consecutive scans during the 24-cycle treatment phase) assessed by blinded independent central review (BICR) of volumetric magnetic resonance imaging. Twenty-four of 58 adults (41%) and 29 of 56 children (52%) had a BICR-confirmed objective response during the 24-cycle treatment phase; in addition, two adults and one child had confirmed responses during long-term follow-up. Median (range) target PN volumetric best response was -41% (-90 to 13) in adults and -42% (-91 to 48) in children. Both cohorts reported significant and clinically meaningful improvement in patient- or parent proxy-reported outcome measures of worst tumor pain severity, pain interference, and health-related quality of life (HRQOL) that began early and were sustained during treatment. The most commonly reported treatment-related adverse events were dermatitis acneiform, diarrhea, and nausea in adults and dermatitis acneiform, diarrhea, and paronychia in children. In ReNeu, the largest multicenter NF1-PN trial reported to date, mirdametinib treatment demonstrated significant confirmed ORRs by BICR, deep and durable PN volume reductions, and early, sustained, and clinically meaningful improvement in pain and HRQOL. Mirdametinib was well-tolerated in adults and children.

Outcomes associated with hip preservation using osteochondral allograft transplants and acetabular labrum reconstruction.

Osteochondral allograft (OCA) transplantation with or without labral reconstruction is considered a hip preservation surgical treatment option for young, active patients. This study aims to report early outcomes for use of OCA and labrum allograft transplants for patients treated for symptomatic femoral head chondral damage and/or acetabular labrum deficiency after implementation of a comprehensive joint restoration approach. 33 patients from a lifelong registry were included for analysis. Outcomes were compared for statistically significant (p < 0.05) differences based on graft preservation methodology (standard preservation [SP] vs. Missouri Osteochondral Preservation System [MOPS]), and based on surfaces treated (femoral head only, labrum only, or femoral head and labrum). Mean follow-up duration was 44.8 (range 12-95) months. Success was documented in 28 (84.8%) patients. For the SP cohort, successful outcomes were documented in 5 cases (50%), while all 23 MOPS cases (100%) were deemed successful at least 1 year after surgery. Hip preservation surgeries performed using MOPS grafts were associated with significantly (p = 0.001; OR = 47x) higher success rates, including significant and clinically meaningful improvements in PROMs at 1 and 2 years after surgery. Revision was performed in 2 patients in the SP cohort and failure requiring total hip arthroplasty was documented in 3 SP patients. Mean time to revision or failure was 23.6 (range 4-43) months. The surfaces treated were significantly associated with failure when comparing patients undergoing a femoral head OCA with or without labral reconstruction to those undergoing labral reconstruction only (p = 0.03; OR = 8.3x). Patients with symptomatic femoral head cartilage loss and/or irreparable acetabular labrum deficiency undergoing femoral head OCA transplantation and/or labral reconstruction with meniscus allografts using MOPS-preserved tissues experienced statistically significant and clinically meaningful improvements in pain and function through at least 2 years after surgery.

Midterm Outcomes After Osteochondral Allograft Transplantation in the Knee Using High–Chondrocyte Viability Grafts

Background: Osteochondral allograft transplantation (OCAT) has become a standard-of-care treatment option for patients with large symptomatic articular defects. Recent advances in allograft science and OCAT protocols have been reported to result in consistently robust outcomes after OCAT in the knee. However, only short-term comparisons have been reported, and analyses are lacking for treatment failure risk factors that account for confounding variables. Hypothesis: Midterm functional graft survival rate would exceed 80% for all OCATs combined, with consideration of risk factors for lower survivorship including older patient age, higher body mass index (BMI), tibiofemoral bipolar OCAT, and nonadherence to prescribed postoperative rehabilitation protocols. Study Design: Case series; Level of evidence, 4. Methods: Patients with outcome data available at ≥5 years after primary OCAT using high chondrocyte–viability (HCV) osteochondral allografts were analyzed according to 2 clinically relevant definitions: (1) initial treatment failure, defined by revision or arthroplasty surgery performed for the primary OCAT at any time point during the study period; and (2) functional graft failure, defined by documented conversion to arthroplasty after primary or revision OCAT at any time point during the study period. Analyses were used to assess outcomes for each definition, separately for age group, sex, obesity status, tobacco use, type of OCAT surgery, osteotomy status, concurrent ligament surgery status, and adherence to postoperative protocols. Kaplan-Meier analyses were used to assess differences in survival rates, and Cox proportional hazards models were used to assess risk factors and multivariable relationships with survival. Patient-reported outcome measures for pain, function, mobility, and satisfaction were also analyzed. Results: Analysis included 137 primary knee OCATs performed in 134 patients with a mean follow-up of 66 months (59 female, 75 male; mean age, 37.8 years; mean BMI, 28.5). The midterm (5- to 8-year) functional graft survival rate for patients undergoing primary OCAT in the knee using HCV grafts was 82% for all cases combined, ranging from 69% for tibiofemoral bipolar HCV OCATs to 89% for patellofemoral bipolar, 94% for multisurface unipolar, and 97% for single-surface unipolar. Initial treatment failure rates (revision or arthroplasty after primary OCAT) and OCAT nonsurvival rates (arthroplasty after primary or revision OCAT) were greater for older patient age, concurrent ligament reconstruction, tibiofemoral bipolar OCAT, and nonadherence to the prescribed postoperative rehabilitation protocols. When adjusted for patients’ age, BMI, and tobacco use status, different surgery types did not demonstrate an increased risk for failure, while concurrent ligament reconstruction and nonadherence did. Patients who experienced functional graft survival after primary OCAT reported significantly greater improvements in PROMIS Physical Function and Mobility (Patient-Reported Outcomes Measurement Information System), International Knee Documentation Committee questionnaire, and Single Assessment Numeric Evaluation scores such that they were significantly higher at final follow-up as compared with patients who required arthroplasty. Patient-reported improvements in pain, function, and mobility exceeded minimal clinically important differences for ≥5 years after primary OCAT. When asked if they were satisfied with primary OCAT surgery, 76.2% of patients were very satisfied or satisfied with their results, while 8.5% were neutral and 15.4% were unsatisfied or very unsatisfied. Conclusion: With use of HCV osteochondral allografts, midterm (5- to 8-year) functional graft survival rates for patients undergoing primary OCAT in the knee were notably higher than previously reported midterm rates for traditional OCATs. When adjusted for patient characteristics, risk factors for nonsurvival included concurrent ligament reconstruction for knee instability and nonadherence to the prescribed postoperative rehabilitation protocols. Patients who experienced functional graft survival for ≥5 years after primary OCAT reported statistically significant and clinically meaningful improvements in pain, function, and mobility.

Patient Experience With Efanesoctocog Alfa for Severe Hemophilia A: Results From the XTEND-1 Phase 3 Clinical Study Exit Interviews

PurposeHemophilia A is a rare bleeding disorder that leads to recurrent hemarthrosis, which can ultimately result in reduced mobility and poor quality of life. Qualitative exit interviews provide insights into patient perspectives and support the interpretation of quantitative trial data, such as patient-reported outcome measures. In the Phase 3 XTEND-1 study (NCT04161495) of efanesoctocog alfa in participants with severe hemophilia A, exit interviews were conducted to understand pre- and post-study experiences with pain and physical functioning and to evaluate participants’ treatment experiences. MethodsIn XTEND-1, participants (≥12 years old) received once-weekly efanesoctocog alfa prophylaxis 50 IU/kg for 52 weeks (Arm A) or on-demand efanesoctocog alfa 50 IU/kg for 26 weeks followed by 26 weeks once-weekly prophylaxis (50 IU/kg; Arm B). Optional qualitative exit interviews were conducted using a semi-structured guide in a subset of participants following study completion. Interviews included open-ended questions about participants’ pre- and post-study experiences with hemophilia A and targeted questions relating to improvements in patient-reported outcomes assessed during XTEND-1, including the Haemophilia Quality of Life Questionnaire for Adults Physical Health subscale (Haem-A-QoL PH). Content validity of the Patient-Reported Outcomes Measurement Information System (PROMIS) Pain Intensity 3a measure was also assessed, particularly the worst pain item. FindingsExit interviews were conducted with 29 of 159 patients enrolled in XTEND-1 (mean [range] age 40 [16−73] years). Of 17 participants enrolled in Arm A, 13 (76.5%) reported a “wearing off” feeling with pre-study treatment, including more aches/pain, breakthrough bleeds, and limited physical activities. Joint pain was the most reported pre-study symptom (96.6%; n = 28/29), followed by a reduced ability to move without pain (89.7%, n = 26/29). Improvements following efanesoctocog alfa prophylaxis in ≥1 Haem-A-QoL PH domain were reported by 89.7% (n = 26/29) of participants, with improvements in joint pain, the ability to move without pain, and painful swellings reported by at least 21 (84%) participants. Participants reported that the PROMIS Pain Intensity 3a items were relevant, clear, and easy to answer. Most participants (96.6%) were “quite satisfied” or “very satisfied” with efanesoctocog alfa prophylaxis. All participants preferred efanesoctocog alfa over pre-study treatment. ImplicationsThe exit interviews demonstrated that once-weekly efanesoctocog alfa prophylaxis resulted in patient-relevant and meaningful improvements in pain and physical functioning, consistent with the quantitative findings from XTEND-1. These results support the validity of the Haem-A-QoL PH and PROMIS Pain Intensity 3a assessed during XTEND-1, demonstrating the potential for change with efficacious treatment. Trial RegistryClinicalTrials.gov Trial Registration NumberNCT04161495 Registry URLhttps://clinicaltrials.gov/study/NCT04161495

P246. Determining time to achieve clinically meaningful improvements in pain and disability following transforaminal lumbar interbody fusion

P246. Determining time to achieve clinically meaningful improvements in pain and disability following transforaminal lumbar interbody fusion

Effectiveness and cost-effectiveness of radiofrequency denervation versus placebo for chronic and moderate to severe low back pain: study protocol for the RADICAL randomised controlled trial

IntroductionLow back pain (LBP) is the leading global cause of disability. Patients with moderate to severe LBP who respond positively to a diagnostic medial nerve branch block can be offered...

The effects of the addition of Mulligan mobilization with movement to exercise on elbow pain and function associated with lateral elbow tendinopathy

BackgroundMulligan mobilization with movement (MWM) and eccentric exercise (EE) have been shown to be effective for the treatment of chronic lateral elbow tendinopathy (LET). However, the addition of MWM to EE effects on LET remained unknown. The objective of the study was to determine the effects of adding of Mulligan mobilization with movement to eccentric exercise for the treatment of LET. MethodsIn this quasi-experimental study, thirty participants with unilateral LET were assigned into two groups: 15 in MWM (received MWM + EE) (7 M and 8 F, mean age 36.8 ± 8.3 years) and 15 in EE (9 M and 6 F, mean age 46 ± 8.1 years). Both groups received education about painful activities and eccentric exercise, while the MWM group received MWM with the same eccentric exercise as the EE group. The visual analog scale (VAS) and the patient-rated tennis elbow evaluation (PRTEE) were used to assess pain and upper limb function, respectively, at baseline and at the end of 4 weeks. The data was analyzed using an independent t-test and a paired t-test. ResultsThere was no significant difference (p > 0.05) between groups at baseline. At the end of 4 weeks, significant and clinically meaningful improvements in pain and function were observed for both groups (p < 0.001); however, MWM group showed much better results in VAS (p < 0.001, d = 1.3) and PRTEE (p < 0.001, d = 5.2) ConclusionThis study showed that adding MWM to eccentric exercise resulted in enhanced pain reduction and improved function of the upper limb.

Assessment of health-related quality of life (HRQoL) in triple-class–exposed patients with relapsed or refractory multiple myeloma (RRMM) treated with linvoseltamab in the LINKER-MM1 trial.

e23185 Background: Linvoseltamab, a B-cell maturation antigen × CD3 bispecific antibody, is being evaluated in LINKER-MM1, a Phase 1/2 study in patients with RRMM (NCT03761108). Early results over 36 weeks of treatment showed promising efficacy and a generally manageable safety profile (Jagannath et al., ASH 2023), and improvement or stability in patient-reported outcomes (PROs) including pain and fatigue (Hoffman et al., ASH 2023). We now report PRO data over a treatment period of 76 weeks. Methods: We evaluated patients in LINKER-MM1 who received the 5-25-200 mg dosing regimen in Phases 1 and 2 (n = 117). Patients ≥18 years old with triple-class exposed RRMM were administered linvoseltamab at Weeks 1 (5 mg), 2 (25 mg), and 3 (200 mg), followed by 200 mg once weekly through Weeks 14 (Phase 2) or 16 (Phase 1), then every 2 weeks until progression. Patients with a very good partial response by Week 24 in Phase 2 transitioned to dosing every 4 weeks. The EORTC QLQ-C30 was administered at baseline, Week 4, and then every 4 weeks. Least squares (LS) mean change from baseline and 95% confidence interval (CI) were estimated at each timepoint and overall on all scales using a mixed effects model for repeated measures. A 10-point change from baseline was considered clinically meaningful. Results were stratified by objective response status (at least partial response). No adjustment for multiplicity was performed; statistical significance is nominal, with LS mean change from baseline considered statistically significant if 95% CI did not cross 0. Results: PRO completion rates were generally ≥80% through Week 44 and dropped slightly after Week 44. LS mean change showed improvement in Global Health Status/QoL at Week 12, reaching the clinically meaningful threshold at Week 44; clinically meaningful improvements were observed on role and social functioning scales at Weeks 24 and 28, respectively. Pain and fatigue significantly improved and reached the clinically meaningful threshold at Weeks 20 and 44, respectively; the clinically meaningful improvement in pain was generally maintained through Week 76. Overall LS mean change in pain was clinically meaningful (-10.2; 95% CI -13.7, -6.7). Among treatment responders, statistically significant improvements were observed on all scales, including clinically meaningful improvement in pain (-11.2; 95% CI -14.7, -7.6). Non-responders had statistically significant worsening in fatigue (9.9; 95% CI 0.8, 19.1); overall change from baseline was not significant on other scales. Conclusions: Over 76 weeks of treatment, improvements in measures of HRQoL including pain and fatigue were reported in patients with triple-class exposed RRMM receiving linvoseltamab; responders showed significant improvements on all scales. These PRO results support a favorable benefit–risk profile of linvoseltamab. Clinical trial information: NCT03761108 .

The Best Exercise Modality and Dose for Reducing Pain in Adults With Low Back Pain: A Systematic Review With Model-Based Bayesian Network Meta-analysis.

OBJECTIVE: To quantify the dose-response relationship between overall and specific exercise modalities and pain, in patients with nonspecific chronic low back pain (LBP). DESIGN: Systematic review with Bayesian network meta-analysis. LITERATURE SEARCH: We searched the Medline, Embase, Web of Science, Cochrane Library, Scopus, and SPORTDiscus databases from inception to June 2023. STUDY SELECTION CRITERIA: We included randomized controlled trials of exercise interventions in adults with nonspecific chronic LBP and at least 1 pain outcome reported at the main trial end point. DATA SYNTHESIS: A random-effects network meta-analysis was conducted. We assessed risk of bias using the Cochrane Risk of Bias Tool 2.0, and used the GRADE approach to judge the certainty of evidence for each outcome. RESULTS: Eighty-two trials were included (n = 5033 participants). We found a nonlinear dose-response relationship between total exercise and pain in patients with nonspecific chronic LBP. The maximum significant response was observed at 920 MET minutes (standardized mean difference = -1.74; 95% credible intervals: -2.43, -1.04). The minimal clinically important difference for achieving meaningful pain improvement was 520 MET minutes per week. The dose to achieve minimal clinically important difference varied by type of exercise; Pilates was the most effective. The certainty of the evidence was very low to moderate for all outcomes. CONCLUSION: The dose-response relationship of different exercise modalities to improve pain in patients with nonspecific chronic LBP had a U-shaped trajectory and low- to moderate-certainty evidence. The clinical effect was most pronounced with Pilates exercise. J Orthop Sports Phys Ther 2024;54(5):1-13. Epub 8 March 2024. doi:10.2519/jospt.2024.12153.

Gastrocnemius Release in the Treatment of Achilles Tendinopathy: A Systematic Review.

The aim of this study is to evaluate the use of isolated gastrocnemius release in the treatment of Achilles tendinopathy. The primary outcome is the change in patient-reported pain outcomes. Secondary outcomes include the change in patient-reported foot and ankle function, ankle range of motion and strength, patient satisfaction and rate of surgical complications. A systematic review was undertaken of studies involving patients treated with an isolated gastrocnemius release for Achilles tendinopathy. Randomised controlled trials, cohort studies, case-control studies and case series were eligible and identified from the following databases: MEDLINE and EMBASE. Isolated gastrocnemius release results in improved patient-reported outcome scores for pain and foot and ankle function. There is an increase in ankle range of motion but a reduction in ankle strength. Patients report a high rate of overall satisfaction. The most common surgical complications are sural nerve injury and wound infection. Isolated gastrocnemius release may offer maintained and clinically meaningful improvements in pain and foot and ankle function with an associated reduction in ankle strength.

Improvements in Patient-Reported Outcomes Through Six Months of Guselkumab Treatment in Patients With Active Psoriatic Arthritis: Real-World Data From the CorEvitas Psoriatic Arthritis/Spondyloarthritis Registry.

Evaluate patient-reported outcomes after 6 months of on-label guselkumab use in patients with rheumatologist-diagnosed active psoriatic arthritis (PsA) enrolled in the CorEvitas PsA/Spondyloarthritis Registry. This analysis includes registry participants who initiated and persisted with on-label guselkumab (after US Food and Drug Administration approval for PsA; 100 mg at weeks 0, 4, and every 8 weeks) at their 6-month follow-up visit (On-Label Persisters). Among patients not meeting response criteria at baseline, responses at 6 months were determined for patient-reported outcomes, including patient-reported pain (0-100 mm visual analog scale), patient global assessment of arthritis + psoriasis (PtGA; 0-100 visual analog scale), and Health Assessment Questionnaire-Disability Index (HAQ-DI; 0-3). Unadjusted, nominal P values were calculated via single-proportion, one-sided test (H0 = 0%; α=0.05). Of 90 On-Label Persisters, most had treatment-resistant PsA (92.2% and 73.3% previously received ≥1 and ≥2 biologic/targeted synthetic disease-modifying antirheumatic drugs, respectively), with mean (SD) baseline patient-reported pain, PtGA, and HAQ-DI scores of 57.0 (24.6), 50.3 (24.4), and 0.9(0.6), respectively. Among those with patient-reported pain and PtGA scores of at least 15 at baseline, 40.2% (33/82) and 46.8% (36/77), respectively, achieved at least 15-mm reductions at 6 months; among those with HAQ-DI scoresof at least 0.35 and more than 0.5 at baseline, respectively, 30.4% (21/69) achieved improvements of at least 0.35 and 10.3% (6/58) achieved scores of 0.5 or lower at 6 months (all nominal P < 0.001). Pain and physical function are important contributors to health-related quality of life. In this real-world population of patients with treatment-resistant PsA and 6 months of persistent guselkumab treatment, clinically meaningful improvements in pain and physical function were achieved by approximately 40% and 30% of patients, respectively.

The effectiveness of cervical transforaminal epidural steroid injections for the treatment of cervical radicular pain: A prospective cohort study reporting 12-month outcomes

ObjectivesTo evaluate the effectiveness of cervical transforaminal epidural steroid injection (CTFESI) for the treatment of unilateral cervical radicular pain. DesignSingle-group prospective cohort study. MethodsOutcomes included ≥50% reductions in Numeric Rating Scale (NRS) for arm pain, ≥30% Neck Disability Index (NDI-5) improvement, health-related quality of life (EQ-5D), global improvement (PGIC), personal goal achievement (COMBI), Chronic Pain Sleep Index (CPSI), and healthcare utilization at one, three, six, and 12 months. Data analysis included descriptive statistics with the calculations of 95% confidence intervals (CIs), contingency table analysis, and multilevel logistic regression (LR) analysis, including a worst-case (WC) sensitivity analysis in which missing data were treated as treatment failure. Participants who were treated surgically were considered failures in the categorical analyses. Results33 consecutively enrolled participants (63.6% females, 51.2 ± 12.2 years of age, BMI 28.3 ± 4.5 kg/m2) were analyzed. Success rates for ≥50% reduction in NRS for arm pain at one, three, six and 12 months were 57.6% (95% CI 40.8–72.8%), 71.9% (95% CI 54.6–84.4%), 64.5% (95% CI 46.9–78.9%), and 64.5% (95% CI 46.9–78.9%). Success rates for ≥30% improvement in NDI-5 were 60.6% (95% CI 43.7–75.3%), 68.8% (95% CI 51.4–82.0%), 61.3% (95% CI 43.8–76.3%), and 71.0% (95% CI 53.4–83.9%). In WC analysis, success rates for ≥50% arm NRS and NDI-5 were 0–4.3% lower between 1 and 12 months. PGIC scores were at least “much improved” or “very much improved,” in 48.4–65.6% of participants between 1 and 12 months. 6.1%, 6.1%, and 3.0% had one, two, or three repeat injections, respectively. 18.2% of participants underwent surgery by 12 months. Participants showed significant improvements in arm NRS and NDI-5 after treatment (p < 0.05), multilevel logistic regression models showed no significant decline in improvements across the follow-up time points (p > 0.05). ConclusionStatistically significant and clinically meaningful improvements in pain and disability were observed after CTFESI for up to 12 months in individuals with unilateral cervical radicular pain.

Teclistamab Improves Patient-Reported Symptoms and Health-Related Quality of Life in Relapsed or Refractory Multiple Myeloma: Results From the Phase II MajesTEC-1 Study

IntroductionPatients with relapsed or refractory multiple myeloma (RRMM) report significantly lower HRQoL compared with patients with newly diagnosed MM and experience further deterioration in HRQoL with each relapse and subsequent treatment. Therefore, consideration of the impact of treatment on HRQoL in addition to clinical outcomes is vital. Patients and MethodsIn the phase I/II MajesTEC-1 (NCT03145181, NCT04557098) study, patients with RRMM who received teclistamab, an off-the-shelf, T-cell redirecting BCMA × CD3 bispecific antibody, had deep and durable responses with manageable safety. HRQoL was assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire core 30-item and the EuroQol 5 Dimension 5 Level descriptive questionnaire. Changes over time from baseline were measured with a repeated measures mixed-effects model. Proportions of patients with clinically meaningful improvement after starting treatment and time to clinically meaningful worsening were assessed. ResultsCompliance was maintained throughout the study. Compared with baseline, positive changes were observed for pain, global health status, and emotional functioning with treatment; other assessments were largely unchanged from baseline. Post hoc analysis showed patients with deeper clinical response generally reported improved HRQoL outcomes. Following an initial decline in HRQoL in some scales, the proportion of patients reporting clinically meaningful improvements increased, while the proportion reporting clinically meaningful worsening decreased over time. Clinically meaningful improvements in pain were reported in ≥40% of patients at most assessment time points. ConclusionsThese results complement previously reported clinical benefits and support teclistamab as a promising therapeutic option for patients with RRMM.

Combined Digital Interventions for Pain Reduction in Patients Undergoing Knee Replacement

Digital technology represents an opportunity to improve outcomes following total knee replacement (TKR). Digitally delivered interventions have been shown to be similar to face-to-face interventions and to increase participation levels in people with osteoarthritis. To assess the effect of a digital technology package in reducing pain compared with usual care following TKR. This randomized clinical trial recruited 102 adults after they received TKR in 3 rehabilitation hospitals in Sydney, Australia, between June 2020 and July 2021. All participants underwent usual care. In addition to usual care, 51 participants received a digital technology package consisting of an exercise app, fitness tracker, and online health coaching. In the usual care group, 51 participants received a fitness tracker but with all notifications turned off and goals for step count, sleep, and active hours removed. Participants were followed up for 12 months (June 2021 to July 2022). The primary outcome was mean knee pain during the past week assessed using a numerical rating scale (range, 0-10, with 10 indicating worst possible pain) at 3 months. In unadjusted analyses, considered primary and based on multiple imputations, independent t tests were used to compare means between groups. Secondary outcomes, including measures of function, activity participation, and quality of life, were analyzed using a generalized estimating equation model that accounted for repeated measurements. Of 102 participants (mean [SD] age, 67.9 [7.2] years; 68 [67%] female; and 92 [90%] White) randomly assigned to intervention or usual care groups, 47 (92%) in each group completed the 3-month follow up. At 3 months, participants in the intervention group demonstrated small but not clinically meaningful improvements in pain compared with the usual care group in the unadjusted intention-to-treat analysis (mean difference, -0.84; 95% CI, -1.59 to -0.10; P = .03). Secondary outcomes indicated a statistically significant reduction in pain intensity, (mean difference, -0.94; 95% CI, -1.82 to -0.06), pain disability (mean difference, -5.42; 95% CI, -10.00 to -0.83), and sedentary behavior (mean difference, -9.76; 95% CI, -19.17 to -0.34) favoring the intervention from baseline to 3, 6, and 12 months. In this randomized clinical trial, a combined digital technology program provided small but not clinically meaningful improvements in pain at 3 months and other longer-term favorable outcomes following TKR compared with usual care. Future studies should tailor digital interventions based on participants' abilities and preferences to ensure that the intervention is appropriate and fosters long-term self-management. Anzctr.org.au Identifier: ACTRN12618001448235.

Effectiveness of Pulsed Radiofrequency Based on the Minimum Clinically Important Differences in Lumbar Spine-Related Pain in Patients without Recent Lumbar Surgery

Pulsed radiofrequency (PRF) has been used for treatment of chronic pain in several body regions, including axial and radicular pain. However, a limited number of reports have specifically demonstrated the effectiveness of PRF for spine-related pain among nonsurgical patients. Therefore, we evaluated the effectiveness of PRF for lumbar spine-associated pain in patients without recent spine surgery, and identified the factors associated with clinically meaningful improvement in pain and quality of life. Records of patients who underwent PRF for lumbar spine-related pain and were followed up over 6months between 2019 and 2022 were retrospectively reviewed. Data on patient demographics, interventional factors, and patient-reported outcomes, such as the numerical rating scale (NRS) and EuroQol Group 5 Dimension 5-Level Quality of Life (EQ-5D-5L), were collected. Patients were divided into 2 groups (responsive and nonresponsive) based on the NRS and EQ-5D-5L scores using the previously reported minimal clinically important difference values of the NRS and EQ-5D-5L as cutoffs, and baseline parameters were compared to identify contributing factors. Forty-three patients were included in the final analysis. The NRS and EQ-5D-5L scores improved significantly at 3 and 6months after PRF compared to baseline. The groups with NRS and EQ-5D-5L improvement over the minimal clinically important difference had significantly higher baseline NRS and EQ-5D-5L scores. Our results demonstrated that PRF improved pain and patient-reported outcomes for spine-related pain for at least 6months in our patient cohort. PRF may be a good option for treating lumbar spine-related issues, even with severe pain and/or dysfunction.

Functional outcomes after open reconstruction or nonoperative management of 81 pathologic acetabular fractures from metastatic bone disease

BackgroundPathologic acetabular fracture secondary to skeletal metastasis may result in debilitating pain, inability to ambulate, and impaired quality of life, which may mark the first period of dependent care in cancer patients. Acetabular reconstruction may involve morbid procedures with increased complication rates. This study aimed to evaluate the evolution of pain, performance status, and ambulation following nonoperative management or open reconstruction of pathologic acetabular fractures. MethodsA retrospective cohort of 2630 adult patients with osseous metastatic disease treated at a high-volume cancer center between 2005 and 2021 was screened for pathologic fractures of the acetabulum. The study outcomes were pain, performance status, and the ability to ambulate. We identified 78 patients (median age, 60 years; 37 female patients [46%]) with 81 fractures. Of these, treatment consisted of open reconstruction (n = 34) or nonoperative management alone (n = 47). The mean follow-up in surviving patients was 3.4 years. ResultsOpen reconstruction was performed more frequently for displaced fractures (P < 0.01), Harrington class III or IV acetabula (P < 0.01), and patients with a performance status ≥3 at hospitalization (P = 0.00). Open reconstruction was associated with clinically meaningful improvements in pain (adjusted odds ratio [aOR], 8.3; 95% CI, 1.4–50.6; P = 0.02) and performance status (aOR, 10.9; 95% CI, 1.7–71.0; P = 0.01) at discharge and a restoration of ambulation (aOR, 7.5; 95% CI, 1.9–29.8; P < 0.01) at final follow-up. ConclusionsIn patients with pathologic acetabular fracture due to osseous metastatic disease, functional improvements in pain, performance status, and ambulation were observed following open acetabular reconstruction in carefully selected patients, with no impact on survival, while noninferior improvements were observed in patients receiving nonoperative management when considering their larger clinical context. Level of evidenceLevel III, therapeutic study.

Poster 365: Initial outcomes after unicompartmental tibiofemoral bipolar osteochondral and meniscus allograft transplantation in the knee using high-viability tissues

Objectives: To report initial outcomes for unicompartmental tibiofemoral bipolar osteochondral allograft transplantation (OCAT) with meniscus allograft transplantation (MAT) using fresh high-cell- viability tissues for treatment of knee articular cartilage defects with meniscus deficiency. The study was designed to test the hypothesis that primary OCAT and MAT using high-viability tissues will be associated with successful short-term (2 to 6 years) outcomes based on statistically significant and clinically meaningful improvements in pain and function in the majority of patients. Methods: With IRB approval and documented informed consent, patients who underwent primary OCAT and MAT for large articular cartilage defects with meniscus deficiency involving at least one femoral condyle, tibial plateau, and meniscus, all of which were opposing (bipolar). Surgeries were defined as Uni when patients underwent OCAT and MAT involving one femoral condyle, tibial plateau, and meniscus in the same compartment or Uni-Plus when patients underwent Uni OCAT and MAT with at least one other OCA transplant to treat a large (&gt;2.5cm2) grade III or IV focal articular cartilage defect of the patella, trochlea, femoral condyle, or tibial plateau. Patients who had at least 2-year follow up data regarding complications, failures, adherence, and patient reported outcome measures (PROMs) were analyzed. Patients who required OCA and/or MAT revision or artificial arthroplasty were defined as treatment failures. Patient reported outcome measures (PROMs) including VAS pain, IKDC, SANE, PROMIS Global Health and Physical Function, were collected at 3 and 6 months and then yearly after transplantation. Outcomes were compared based on patient sex, age, and BMI, tobacco use, previous and concurrent procedures, differences in number of surfaces transplanted (Uni vs Uni-Plus), and adherence. Significance was set at P &lt; 0.05. Differences in PROMs were also assessed for minimum clinically important differences. Results: Seventy-six patients (n=52 males; 68%) met inclusion criteria (mean followup = 52 months; median = 56 months; range, 24-70 months). Mean age was 41.1 years (range, 15-69 years) and mean body mass index (BMI) was 28.9 kg/m2 (range, 17-46). Forty-eight patients underwent OCAT(s) in addition to Uni (Uni-Plus). Eight patients (10.5%) underwent concurrent ACL reconstruction, and 28 patients (36.8%) underwent ipsilateral lower extremity osteotomy in order to address co-morbidities. Twenty-three patients (30.3%) were documented to be non-adherent during the first year after transplantation. Initial (&gt;2-year) success rate was 77.6% with 8 patients (10.5%) undergoing OCA and/or MAT revision and 9 patients (11.8%) converted to arthroplasty. Variables associated with increased risk for treatment failure (revision or arthroplasty) included ipsilateral osteotomy (p = .046; OR = 3.3), ipsilateral concurrent procedure (p = .0057; OR = 5.5), and non-adherence (p = .0009; OR = 7.2). None of the patients undergoing OCA and/or MAT revision surgery in the present study required arthroplasty at the time of data analysis such that overall success rate for primary and revision unicompartmental bipolar OCA plus MAT was 88.2%. There were statistically significant (p &lt; .0001) and clinically important improvements from preoperative levels for all patient reported outcomes at each annual follow-up time point. Conclusions: Unicompartmental tibiofemoral bipolar osteochondral and meniscus allograft transplantation can result in successful short-term (2 to 6 years) outcomes and satisfaction in the majority (78%) of patients. Primary MOPS-preserved OCAT and MAT for treatment of femoral condyle and tibial plateau articular cartilage defects with concurrent meniscus deficiency was associated with statistically significant and clinically meaningful improvements in patient-reported measures of pain and function.

An impairment-based physical therapy program for runners with femoroacetabular impingement (FAI).

Purpose. Running is a common sport and recreational activity in the United States. Due to its dysfunctional implication in runners, femoroacetabular impingement (FAI) is increasingly recognized as a problematic source of anterior hip pain. The purpose of this case series was to describe an impairment-based physical therapy intervention in non-professional runners with FAI.&#x0D; Materials and methods. Two males, non-professional runners with a mean age of 28.5± 2.1 years, both with a diagnosis of femoroacetabular impingement (FAI), were treated with manual therapy, dynamic neuromuscular stabilization (DNS), and functional training. At initial evaluation, subjects were examined and completed self-reported outcome measures including the visual analog scale (VAS), and the patient-specific functional scale (PSFS). At discharge, they completed the same outcome measures along with the global rating of change (GROC) questionnaire.&#x0D; Results. Both subjects showed clinically meaningful improvement in pain and function above the minimal clinically important difference (MCID). Upon discharge, subject 1 had a 86% reduction in VAS score, a 75% improvement in PSFS score, and a GROC score of 6; subject 2 had a 88% reduction in VAS, a 64% improvement in PSFS, and a GROC score of 5.&#x0D; Conclusion. The overall improvement observed in this study was clinically meaningful to subjects who participated, however, because a cause and effect cannot be inferred from case series studies, follow-up randomized clinical/controlled trials are recommended to further investigate the studied intervention on runners with FAI.

Acupuncture versus massage for pain in patients living with advanced cancer: The IMPACT randomized clinical trial.

12101 Background: Pain represents a challenging symptom for patients living with advanced cancer and is often associated with fatigue and insomnia. While American Society for Clinical Oncology clinical guidelines recommend acupuncture and massage for oncological pain management, the long-term comparative effectiveness between these two therapies is unknown, particularly among those living with advanced cancer. Methods: We conducted a pragmatic randomized clinical trial to compare acupuncture and massage for musculoskeletal pain among patients living with advanced cancer who experienced at least moderate pain and had a life expectancy of at least six months. Patients received weekly acupuncture or massage treatments for ten weeks, followed by monthly booster sessions up to 26 weeks. The primary endpoint was the change in worst pain intensity score measured by the Brief Pain Inventory (BPI) from baseline to 26 weeks. The secondary outcomes included pain-related interference (BPI), pain medication usage, patient-reported fatigue, insomnia, and quality of life. Analyses were performed using linear mixed models adhering to intent to treat. Results: Among 298 participants (mean age [SD] 58.7 [14.1] years, baseline worst pain 6.6 [1.5], 67.1% women, 25.9% non-white, 15.4% Hispanic, cancer types [21.5% hematologic, 19.8% breast, 14.4% gynecological, and 11.7% gastrointestinal, 9.7% lung, and 9.7% prostate]), 242 (81.2%) completed the primary endpoint. From baseline to week 26, acupuncture reduced worst pain by 2.53 points (95% CI 2.15-2.92) while massage reduced worst pain by 3.01 points (95% CI 2.63-3.38); the between-group difference was not significant (0.48, 95% CI -0.03-0.98, p = 0.066). Both treatments reduced pain-related interference and pain medication usage and improved comorbid fatigue, insomnia, and quality of life to a similar degree without between-group differences. Adverse events were mild: bruising was reported by 9 (6.5%) acupuncture patients, and transient soreness was reported by 21(15.1%) massage patients and 8 (5.8%) acupuncture patients. Despite receiving close in-person treatment, no known COVID-19 transmission was reported between patients and providers. Conclusions: Among patients living with advanced cancer, acupuncture and massage produced similar clinically meaningful improvements in pain and comorbid fatigue and insomnia, decreased use of pain medications, and improved quality of life. Integrating these non-pharmacological therapies into comprehensive cancer care can improve symptom management and quality of life for the ever-growing number of patients living with advanced cancer as a chronic illness. Clinical trial information: NCT04095234 .