Thomas J Schnitzer's research while affiliated with Northwestern University and other places

Publications (272)

Preprint
Full-text available
We evaluated the incremental effect of opioids on chronic back pain patients (CBP) by comparing 50 CBP on opioid therapy (CBP+O; opioid duration >= 3months) to pain intensity-, pain duration-, age-, and sex- matched CBP who were not on opioids (CBP-O). Participants completed the NIH Toolbox's cognitive, affective, sensory, and motor components. Sev...
Article
Full-text available
Introduction: A recent phase 3, randomized, placebo- and tramadol-controlled trial (56-week treatment/24-week safety follow-up) demonstrated efficacy of tanezumab 10 mg in patients with chronic low back pain (CLBP) and a history of inadequate response to standard-of-care analgesics. Here, we report on the clinical meaningfulness of treatment respo...
Article
Introduction: We sought to identify and characterize distinct responder profiles among osteoarthritis (OA) subjects treated with tanezumab, nonsteroidal anti-inflammatory drugs (NSAIDs), or placebo. Methods: Subject-level data were derived from three randomized, double-blind, placebo- or NSAID-controlled trials of tanezumab in subjects with mode...
Article
Objective To assess onset of effect in three placebo- or nonsteroidal anti-inflammatory drug (NSAID)-controlled trials of tanezumab in patients with moderate-to-severe osteoarthritis. Methods Post-hoc nonparametric Kaplan–Meier analyses were used to estimate median time to first improvement and to sustained improvement in Western Ontario and McMas...
Article
Full-text available
Background: Osteoarthritis (OA) is typically associated with pain, but many patients are not treated. Methods: This point in time study explored factors associated with treatment status, using logistic regression of data from the Adelphi OA Disease Specific Programme conducted in the United States. Patients' treatment status was based on physici...
Article
Chronic pain is a multidimensional pathological state. Recent evidence suggests that specific brain properties and patients’ psychological and physical traits are distorted in chronic pain patients. However, the relationship between these alterations and pain dimensions remains poorly understood. Here we first evaluated multiple dimensions of chron...
Article
Objective To define meaningful within-patient change (MWPC) in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Methods Data were analyzed separately from 3 phase 3 clinical trials (ClinicalTrials.gov: NCT02697773 , NCT02709486 , NCT02528188 ) of tanezumab, a novel treatment intended for the relief of signs and symptoms...
Article
Full-text available
IntroductionSatisfaction with medications prescribed for osteoarthritis (OA) varies; this study aimed to determine the factors associated with satisfaction in US patients and their physicians.Methods This point-in-time study used the Adelphi OA Disease Specific Programme (physicians identified from public lists reported on nine consecutive patients...
Chapter
Spinal cord injury (SCI) is associated with rapid and profound bone loss around skeletal regions of the knee, a common site of bone fracture in individuals with SCI. Numerous radiographic studies using 2D and 3D modalities have characterized bone loss at the knee after SCI. Cross-sectional and longitudinal studies all demonstrate that bone loss occ...
Article
Full-text available
Aim To assess impact of pre-specified patient characteristics on efficacy and safety of subcutaneous tanezumab in patients with osteoarthritis (OA). Methods Data were pooled from two (efficacy; N = 1545) or three (safety; N = 1754) phase 3 placebo-controlled trials. Change from baseline to week 16 in Western Ontario and McMaster Universities Osteo...
Article
Full-text available
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) explor...
Article
Full-text available
The objective of this study is to validate a placebo pill response predictive model - a biosignature - that classifies chronic pain patients into placebo-responders (predicted-PTxResp) and non-responders (predicted-PTxNonR), and test whether it can dissociate placebo and active treatment responses. The model, based on psychological and brain functi...
Article
Full-text available
Background Preventing transition to chronic back pain (CBP) is a long-sought strategy that could rescue patients from prolonged suffering. Recent rodent and human brain imaging studies suggest involvement of sexually dimorphic, dopaminergic-motivational, mesolimbic circuits in the transition to chronic pain (tCBP), and hint that the combination of...
Article
A single infusion of zoledronic acid (ZOL) after acute spinal cord injury (SCI) attenuates bone loss at the hip (proximal femur) and knee (distal femur and proximal tibia) for at least 6 months. The objective of this study was to examine the effects of timing and frequency of ZOL over 2 years. In this double‐blind, placebo‐controlled trial, we rand...
Article
Full-text available
Objective This pooled analysis of 3 randomized, placebo‐controlled trials (16─24 week treatment; 8─24 week follow‐up) assessed safety of subcutaneous tanezumab (2.5─10 mg every 8 weeks) in 1840 patients with hip or knee osteoarthritis. Methods Overall treatment‐emergent adverse events (TEAEs) and TEAEs of abnormal peripheral sensation (APS) were p...
Article
Full-text available
IntroductionThe opiate epidemic has severe medical and social consequences. Opioids are commonly prescribed in patients with chronic pain, and are a main contributor to the opiate epidemic. The adverse effects of long-term opioid usage have been studied primarily in dependence/addiction disorders, but not in chronic pain. Here, we examine the added...
Article
Full-text available
Most information about distal radius microstructure is based on the non-dominant forearm, with little known about the factors that contribute to bilateral asymmetries in the general population, or what factors may influence bilateral changes over time. Here, we analyzed bilateral high resolution peripheral quantitative computed tomography (HRpQCT)...
Article
Objective Assessment of long‐term safety and 16‐week efficacy of subcutaneous tanezumab in patients with hip or knee OA. Methods This was a randomized, double‐blind, double‐dummy, active‐controlled (nonsteroidal antiinflammatory drug [NSAID]), phase III safety trial (56‐week treatment/24‐week post‐treatment follow‐up) in adults receiving stable do...
Preprint
Full-text available
Most information about distal radius microstructure is based on the non-dominant forearm, with little known about the factors that contribute to bilateral asymmetries in the general population, or what factors may influence bilateral changes over time. Here, we analyzed bilateral longitudinal high resolution peripheral quantitative computed tomogra...
Article
Sex differences in the quality and prevalence of chronic pain are manifold, with women generally presenting higher incidence and severity. Uncovering chronic pain-related sex differences inform neural mechanisms and may lead to novel treatment routes. In a multicenter morphological study (total n = 374), we investigated whether the shape of subcort...
Article
Full-text available
Osteoarthritis (OA) manifests with chronic pain, motor impairment, and proprioceptive changes. However, the role of the brain in the disease is largely unknown. Here, we studied brain networks using the mathematical properties of graphs in a large sample of knee and hip OA (KOA, n = 91; HOA, n = 23) patients. We used a robust validation strategy by...
Article
Spinal cord injury (SCI) is associated with bone fragility and fractures around the knee. The purpose of this investigation was to validate a computed tomography (CT) based finite element (FE) model of the proximal tibia and distal femur under biaxial loading, and to retrospectively quantify the relationship between model predictions and fracture i...
Article
Full-text available
The interaction between osteoarthritis (OA) pain and brain properties remains minimally understood, although anatomical and functional neuroimaging studies suggest that OA, similar to other chronic pain conditions, may impact as well as partly be determined by brain properties. Here, we studied brain grey matter (GM) properties in OA patients sched...
Article
Background Osteoarthritis (OA) causes pain, disability and impaired quality of life. Tanezumab, a monoclonal antibody against nerve growth factor, is in development for the management of OA pain. Two randomised, placebo-controlled studies with a primary aim of assessing the efficacy and safety of subcutaneously administered tanezumab were recently...
Article
Full-text available
Importance Opioid prescriptions for treatment of pain in emergency departments (EDs) are associated with long-term opioid use. The temporal pattern of opioid prescribing in the context of the opioid epidemic remains unknown. Objective To examine the temporal pattern of opioid prescribing within an ED for varying pain conditions between 2009 and 20...
Article
Although strong evidence exists that certain activities can increase bone density and structure in people, it is unclear what specific mechanical factors govern the response. This is important because understanding the effect of mechanical signals on bone could contribute to more effective osteoporosis prevention methods and efficient clinical tria...
Article
Objective To examine the onset and maintenance of efficacy of subcutaneous tanezumab for pain relief and functional improvement in difficult-to-treat patients with moderate-to-severe osteoarthritis (OA) in a 16-week dose-titration study (NCT02697773). Methods Patients were randomized to placebo (placebo group) or tanezumab 2.5 mg at baseline and w...
Article
Full-text available
A significant proportion of osteoarthritis (OA) patients continue to experience moderate to severe pain after total joint replacement (TJR). Preoperative factors related to pain persistence are mainly studied using individual predictor variables and distinct pain outcomes, thus leading to a lack of consensus regarding the influence of preoperative...
Preprint
Full-text available
Preventing transition to chronic back pain (CBP) is an ideal strategy that would rescue patients from years to a lifetime of suffering with pain. Recent studies suggest involvement of sexually-dimorphic dopaminergic-motivational circuits in the transition to chronic pain (tCBP), and hints the combination of carbidopa/levodopa and naproxen (LDP+NPX)...
Preprint
Full-text available
A significant proportion of osteoarthritis (OA) patients continue to experience moderate to severe pain after total joint replacement (TJR). Preoperative factors related to pain persistence are mainly studied using individual predictor variables and distinct pain outcomes, thus leading to a lack of consensus regarding the influence of preoperative...
Article
Full-text available
Psychological and personality factors, socioeconomic status, and brain properties all contribute to chronic pain but have essentially been studied independently. Here, we administered a broad battery of questionnaires to patients with chronic back pain (CBP) and collected repeated sessions of resting-state functional magnetic resonance imaging (fMR...
Article
Full-text available
Objective: To prospectively assess efficacy, general and joint safety of fasinumab, an anti-nerve growth factor monoclonal antibody, in osteoarthritis (OA) pain. Methods: Patients with moderate-to-severe OA pain (knee or hip) and history of inadequate response or intolerance to analgesics were randomized to fasinumab 1-mg, 3-mg, 6-mg, 9-mg or pl...
Article
Study design: Non-randomized open-label clinical trial of oral alendronate after teriparatide therapy in people with spinal cord injury (SCI) and low bone mineral density (BMD). Objectives: To determine if alendronate would prevent bone loss after discontinuation of teriparatide. Setting: Outpatient research clinic at Northwestern University F...
Article
This review expounds on types and properties of biomarkers for chronic pain, given a mechanistic model of processes underlying development of chronic pain. It covers advances in the field of developing biomarkers for chronic pain, while outlining the general principles of categorizing types of biomarkers driven by specific hypotheses regarding unde...
Article
Full-text available
Tive L, Bello AE, Radin D, et al. J Pain Res. 2019;12:975 —995. The authors have advised there is an error in the middle panels of Figure 6 on page 985. Both panels read “Patients with severe OA” the panel on the right should read “Patients with less severe OA”. The correct Figure 6 is shown below. Read the original article
Article
Objective To assess the efficacy and safety of the anti‐interleukin (IL)‐1α/β dual variable domain immunoglobulin lutikizumab (ABT‐981) in subjects with knee osteoarthritis (OA) and evidence of synovitis. Methods Subjects (N=350; 347 analyzed) with Kellgren‐Lawrence grade 2–3 knee OA and synovitis (determined by magnetic resonance imaging [MRI] or...
Article
Full-text available
Objective To update the 1997 OMERACT-OARSI (Outcome Measures in Rheumatology-Osteoarthritis Research Society International) core domain set for clinical trials in hip and/or knee osteoarthritis (OA). Methods An initial review of the COMET database of core outcome sets (COS) was undertaken to identify all domains reported in previous COS including...
Article
Full-text available
Objective To assess the uptake of the OMERACT-OARSI (Outcome Measures in Rheumatology- Osteoarthritis Research Society International) core outcome set (COS) domains in hip and/or knee osteoarthritis (OA) trials. Methods There were 382 trials of hip and/or knee OA identified from the ClinicalTrial.gov registry from 1997 to 2017. Frequency of COS ad...
Article
Computed tomography and finite element modeling were used to assess bone structure at the knee as a function of time after spinal cord injury. Analyzed regions experienced degradation in stiffness, mineral density, and content. Changes were well described as an exponential decay over time, reaching a steady state 3.5 years after injury. Introducti...
Article
Development of new pharmacological treatments for osteoarthritis that address unmet medical needs in a competitive market place is challenging. Bayesian approaches to trial design offer advantages in defining treatment benefits by addressing clinically relevant magnitude of effects relative to comparators and in optimizing efficiency in analysis. S...
Preprint
Full-text available
Psychological and personality factors, socioeconomic status, and brain properties all contribute to chronic pain but have essentially been studied independently. Here, we administered a broad battery of questionnaires to patients with chronic back pain (CBP). Clustering and network analyses revealed four orthogonal dimensions accounting for 60% of...
Preprint
Full-text available
Although there is strong evidence that certain activities can increase bone density and structure in some individuals, it is unclear what specific mechanical factors govern the response. This is important because understanding the effect of mechanical signals on bone could contribute to more effective osteoporosis prevention methods and efficient c...
Article
Full-text available
The placebo response is universally observed in clinical trials of pain treatments, yet the individual characteristics rendering a patient a 'placebo responder' remain unclear. Here, in chronic back pain patients, we demonstrate using MRI and fMRI that the response to placebo 'analgesic' pills depends on brain structure and function. Subcortical li...
Article
Objective: This study tested whether galcanezumab, a humanized monoclonal antibody with efficacy against migraine, was superior to placebo for the treatment of mild or moderate osteoarthritis (OA) knee pain. Method: In a multicenter, double-blind, placebo- and celecoxib-controlled trial, patients with moderate to severe OA pain were randomized t...
Article
Spinal cord injury (SCI) is associated with marked bone loss and an increased risk of fracture. We randomized 61 individuals with chronic SCI and low bone mass to receive either: teriparatide 20 µg/day plus sham vibration 10 min/day (n = 20), placebo plus vibration 10 min/day (n = 20), or teriparatide 20 µg/day plus vibration 10 min/day (n = 21). P...
Article
Objective: To evaluate intraarticular onabotulinumtoxinA 400 U and 200 U in reducing symptoms of knee osteoarthritis (OA) in patients with nociceptive pain. Design: A multicenter, double-blind, randomized, placebo-controlled study was conducted in adults with knee OA and a painDETECT questionnaire score of ≤12 (indicating nociceptive pain). Pati...
Article
Development and maintenance of chronic pain is associated with structural and functional brain reorganization. However, few studies have explored the impact of drug treatments on such changes. The extent to which long-term analgesia is related to brain adaptations and its effects on the reversibility of brain reorganization remain unclear. In a ran...
Preprint
Full-text available
Placebo response is universally observed in randomized controlled trials (RCTs), yet these effects are commonly dismissed as consequences of uncontrollable confounds. In this prospective neuroimaging-based RCT performed in chronic back pain patients, we demonstrate that the intensity, but not quality, of pain is diminished with placebo pill ingesti...
Article
Full-text available
Experiences and memories are often mismatched. While multiple studies have investigated psychological underpinnings of recall error with respect to emotional events, the neurobiological mechanisms underlying the divergence between experiences and memories remain relatively unexplored in the domain of chronic pain. Here we examined the discrepancy b...
Conference Paper
Background The safety and efficacy of galcanezumab, a monoclonal antibody directed against CGRP, were assessed in a phase 2 clinical trial NCT02192190 in patients with moderate to severe osteoarthritis (OA) knee pain. Patients were randomized to placebo, galcanezumab (5, 25, 120 and 300 mg subcutaneously every 4 weeks, at weeks 0 and 4) or celecoxi...
Article
Full-text available
Introduction: The management of pain associated with chronic musculoskeletal conditions represents a significant challenge for the clinician. There remains a need for novel medications that have a significant analgesic benefit and are also safe and well tolerated. Both pre-clinical and clinical data have provided evidence of the role of nerve growt...
Article
Full-text available
Background Few effective pharmacological treatment options exist for chronic back pain, the leading cause of disability in the US, and all are associated with significant adverse effects. Objective To determine the efficacy and safety of D-cycloserine, a partial agonist to the N-methyl-D-aspartate receptor, in the treatment of chronic low back pai...
Data
Complete list of inclusion and exclusion criteria. (DOCX)
Article
Full-text available
Placebo response in the clinical trial setting is poorly understood and alleged to be driven by statistical confounds, and its biological underpinnings are questioned. Here we identified and validated that clinical placebo response is predictable from resting-state functional magnetic-resonance-imaging (fMRI) brain connectivity. This also led to di...