Publications by authors named "Marc Hochberg"

300 Publications

Depressive symptom heterogeneity among older adults after hip fracture.

Age Ageing 2021 Aug 16. Epub 2021 Aug 16.

Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, MD, USA.

Objective: to evaluate patterns of depressive symptoms after hip fracture and examine their impact on functional recovery.

Methods: participants (n = 304) included older adults from the Baltimore Hip Studies 7th cohort who experienced a hip fracture. Depressive symptoms were measured at baseline or 2-, 6- or 12-month post-hip fracture using the 20-item Center for Epidemiologic Studies Depression scale. Gait speed was measured after hip fracture at 2-, 6- or 12-month follow-up. Latent class analysis was used to identify individuals with similar patterns of depressive symptoms after hip fracture. Item response probabilities characterised symptom profiles, and posterior probability estimates were used to assign participants to a baseline depressive symptom subtype. Weighted estimated equations compared post-fracture gait speed between baseline symptomatic and asymptomatic groups.

Results: four patterns of depressive symptoms were identified: asymptomatic (50.8%), somatic (28.6%), melancholic (11.4%) and anhedonic (9.2%). The somatic subtype was characterised by difficultly concentrating and reduced energy and movement, whereas anhedonic symptoms were associated with the inability to experience pleasure. Melancholic symptoms corresponded to anhedonia, decreased physical activity and other psychological and somatic complaints. Compared with the asymptomatic group, somatic symptoms were consistently associated with slower gait speed, -0.03 metres per second (m/s) and between-group differences for melancholic symptomology were as large as -0.05 m/s, but the associations were not statistically significant.

Conclusion: findings demonstrate unique depressive symptom subtypes in older adults after hip fracture and provide confirmatory evidence of unique clinical phenotypes; however, their impact on functional recovery after hip fracture remains unclear.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ageing/afab168DOI Listing
August 2021

Sports with a Bat or Racket are Not Associated with Thumb-base Osteoarthritis.

J Athl Train 2021 Aug 17. Epub 2021 Aug 17.

Timothy E. McAlindon, MD, MPH, Chief, Division of Rheumatology, Allergy, & Immunology, Tufts Medical Center, Boston, MA, USA,

Context: Repetitive joint use is a risk factor for osteoarthritis, which is a leading cause of disability. Sports requiring a bat or racket to perform repetitive high-velocity impacts may increase the risk of thumb-base osteoarthritis. However, this hypothesis remains untested.

Objective: To determine if a history of participation in racket or bat sports is associated with the prevalence of thumb-base osteoarthritis.

Design: Descriptive epidemiology study.

Setting: Osteoarthritis Initiative. Four clinical sites in the United States.

Participants: We included men and women from the recruited from the community. Eligible participants had dominant hand radiographic readings, hand symptom assessments, and historical physical activity survey data.

Main Outcome Measures: A history of exposure to racket or bat sports (baseball/softball, racquetball/squash, badminton, table tennis, tennis [doubles/singles]) was based on self-reported recall data covering 3 age ranges (12-18 years, 19-34 years, 35-49 years). Prevalent radiographic thumb-base osteoarthritis was defined as someone with Kellgren-Lawrence grade≥2 in the first carpometacarpal joint or scaphotrapezoidal joint at the OAI baseline visit. Symptomatic thumb-base osteoarthritis was defined as the presence of radiographic osteoarthritis and hand/finger symptoms.

Results: In total, we included 2309 participants. Among 1049 men, 355 (34%) and 56 (5%) had radiographic or symptomatic thumb-base osteoarthritis, respectively; and among 1260 women, 535 (42%) and 170 (13%), respectively. After adjusting for age, race, and education level, we found no statistically significant associations between a history of any racket or bat sport participation and thumb-base osteoarthritis (radiographic or symptomatic; odds ratios range from 0.82 to 1.34).

Conclusions: Within a community-based cohort, a self-reported history of participation in racket or bat sports was not associated with an increased odds of having radiographic or symptomatic thumb-base osteoarthritis in the dominant hand.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4085/1062-6050-0208.21DOI Listing
August 2021

Response letter to the Editor.

Semin Arthritis Rheum 2021 May 8. Epub 2021 May 8.

University of Maryland School of Medicine, Baltimore, MD, United States.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.semarthrit.2021.05.001DOI Listing
May 2021

Long-term structural and symptomatic effects of intra-articular sprifermin in patients with knee osteoarthritis: 5-year results from the FORWARD study.

Ann Rheum Dis 2021 May 7. Epub 2021 May 7.

Rheumatology, Leeds Teaching Hospitals NHS Trust, Leeds, UK.

Objective: The FORWARD (FGF-18 Osteoarthritis Randomized Trial with Administration of Repeated Doses) trial assessed efficacy and safety of the potential disease-modifying osteoarthritis drug (DMOAD) sprifermin in patients with knee osteoarthritis. Here, we report 5-year efficacy and safety results.

Methods: Patients were randomised to intra-articular sprifermin 100 µg or 30 µg every 6 months (q6mo) or 12 months, or placebo, for 18 months. The primary analysis was at year 2, with follow-up at years 3, 4 and 5. Additional post hoc exploratory analyses were conducted in patients with baseline minimum radiographic joint space width 1.5-3.5 mm and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain 40-90, a subgroup at risk (SAR) of progression.

Results: 378 (69%) patients completed the 5-year follow-up. A significant dose-response in total femorotibial joint cartilage thickness with sprifermin (trend test, p<0.001) and a 0.05 mm mean difference with sprifermin 100 µg q6mo versus placebo (95% CI 0.00 to 0.10; p=0.015) were sustained to year 5. WOMAC pain scores improved ~50% from baseline in all groups. No patient in the 100 µg q6mo group had replacement of the treated knee. 96%-98% of patients receiving sprifermin and 98% placebo reported adverse events, most were mild or moderate and deemed unrelated to treatment. Adverse event-related study withdrawals were <10%. Differentiation in WOMAC pain between sprifermin 100 µg q6mo and placebo in the SAR (n=161) at year 3 was maintained to year 5 (-10.08; 95% CI -25.68 to 5.53).

Conclusion: In the longest DMOAD trial reported to date, sprifermin maintained long-term structural modification of articular cartilage over 3.5 years post-treatment. Potential translation to clinical benefit was observed in the SAR.

Trial Registration Number: NCT01919164.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/annrheumdis-2020-219181DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8292562PMC
May 2021

The effects of sprifermin on symptoms and structure in a subgroup at risk of progression in the FORWARD knee osteoarthritis trial.

Semin Arthritis Rheum 2021 04 11;51(2):450-456. Epub 2021 Mar 11.

Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, and NIHR Leeds Biomedical Research Centre, Chapel Allerton Hospital, Leeds, UK. Electronic address:

Objective: To assess pain outcomes and cartilage thickness change in a subgroup at risk (SAR) of further progression in the FORWARD trial of knee osteoarthritis patients treated with sprifermin.

Methods: Patients were randomised 1:1:1:1:1 to: sprifermin 100 µg every 6 months (q6mo), 100 µg q12mo, 30 µg q6mo, 30 µg q12mo, or placebo for 18 months. SAR was defined as baseline medial or lateral minimum joint-space width (mJSW) 1.5-3.5 mm and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score 40-90 units. Follow-up to 3 years was included in the analysis. Treatment benefit was explored by repeated measures, linear dose-effect trends by timepoint.

Results: The SAR comprised 161 (29%) of 549 patients. Mean difference (95% CI) in WOMAC pain at year 3 for sprifermin 100 µg q6mo vs placebo SAR was -8.75 (-22.42, 4.92) for SAR vs 0.97 (-6.22, 8.16) for the intent-to-treat population. SAR placebo patients lost more cartilage over 2 years than the modified ITT (mITT) placebo arm (mean change from baseline, mm [SD]: -0.05 [0.10] vs -0.02 [0.07]). Net total femorotibial joint thickness gain with sprifermin 100 µg q6mo (adjusted mean difference from placebo [95% CI] was similar in the SAR and in the mITT group: 0.06 [0.01, 0.11] vs 0.05 [0.03, 0.07]).

Conclusions: Selection for low mJSW and moderate-to-high pain at baseline resulted in more rapid disease progression and demonstrated translation of structure modification (with maintained net benefit on total cartilage thickness) into symptomatic benefit. This subgroup may represent a target population for future trials.

Clinical Trial Registration: NCT01919164.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.semarthrit.2021.03.005DOI Listing
April 2021

Change in vertebral strength and bone mineral density in men and women over the year post-hip fracture: a subgroup analysis.

Arch Osteoporos 2021 02 22;16(1):37. Epub 2021 Feb 22.

Department of Epidemiology and Public Health, School of Medicine, University of Maryland Baltimore, 660 West Redwood Street, Suite 200, Baltimore, MD, 21201, USA.

This study examines changes in bone density and strength in the spine over the year after hip fracture to see if there are differences in the changes between men and women. Results show losses in the spine that may increase the risk of subsequent vertebral fractures, particularly for women.

Purpose: Compare changes over the first year post-hip fracture in vertebral bone mineral density (BMD) and compressive strength, measured from quantitative computed tomography (QCT) scans of the spine (T12-L1), between women and men.

Methods: QCT scans were performed on 37 participants (21 men and 16 women) at 2 and 12 months post-hip fracture as part of an ancillary observational study of hip fracture recovery in older community-dwelling men and women. Vertebral BMD and compressive strength were calculated using VirtuOst® (O.N. Diagnostics, Berkeley, CA). Unpaired t-tests were used to compare men and women with respect to baseline demographics, measurements of BMD and bone strength for the whole vertebra and the cortical and trabecular compartments, and any changes in these parameters between months 2 and 12.

Results: At 2 months post-fracture, there were no significant sex differences in any measurements of vertebral strength or BMD. Between months 2 and 12, vertebral strength decreased significantly in women (- 3.8%, p < 0.05) but not in men (- 2.3%, p < 0.20), vertebral trabecular BMD decreased similarly in both sexes (- 5.7% women; - 6.0% men), but cortical BMD did not change for either sex.

Conclusion: Despite the small sample size, these findings suggest that appreciable loss of vertebral trabecular bone can occur for both sexes in the year following hip fracture, which may increase the risk of subsequent vertebral fracture, particularly for women.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11657-021-00907-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8183184PMC
February 2021

Medical overuse of therapies and diagnostics in rheumatology.

Clin Rheumatol 2021 May 10;40(5):2087-2094. Epub 2021 Feb 10.

Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Maryland School of Medicine, 10 S Pine Street, MSTF room 8.34, Baltimore, MD, 21201, USA.

Medical overuse leads to a burden on healthcare costs and potentially is harmful to patients. We wanted to address medical overuse in musculoskeletal disease and rheumatology. We performed a systemic literature review from PubMed and Embase to study medical overuse. On the initial screen, 1499 studies were identified, 839 of them were related to medical overuse. Out of these, 52 were related to overuse in musculoskeletal diseases. Finally, 20 articles were chosen for this systemic review that reported overuse in rheumatology. The article identifies issues with overtesting, including the use of dual-energy X-ray absorptiometry to screen for osteoporosis in women younger than 65 years old and the use of magnetic resonance imaging to evaluate for osteoarthritis. Studies related to overtreatment reported over-prescription of vitamin D supplements resulting in vitamin D toxicity and increased risk of inappropriate prescriptions in patients with osteoarthritis and rheumatoid arthritis. Overtreating osteoporosis was reported after industry-sponsored education. Articles describing methods to reduce overuse included a study showing the reduction of unnecessary dual-energy X-ray absorptiometry scans after the introduction of the Choosing Wisely Campaign. Our findings suggest that there is some evidence that overtesting and overtreatment may be present in the field of rheumatology. This review aims to highlight this and help rheumatologists to be aware of overuse practices and provide appropriate evidence-based healthcare.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10067-021-05638-2DOI Listing
May 2021

Long-Term Safety and Efficacy of Subcutaneous Tanezumab Versus Nonsteroidal Antiinflammatory Drugs for Hip or Knee Osteoarthritis: A Randomized Trial.

Arthritis Rheumatol 2021 07 7;73(7):1167-1177. Epub 2021 Jun 7.

Pfizer, Inc., Groton, Connecticut.

Objective: To assess the long-term safety and 16-week efficacy of subcutaneous tanezumab in patients with hip or knee osteoarthritis (OA).

Methods: This was a phase III randomized, double-blind, active treatment-controlled (using nonsteroidal antiinflammatory drugs [NSAIDs] as the active treatment control) safety trial of tanezumab (56-week treatment/24-week posttreatment follow-up) in adults who were receiving stable-dose NSAID therapy at the time of screening and who had Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and physical function scores of ≥5; patient global assessment (PtGA) of OA of fair, poor, or very poor; history of inadequate pain relief with standard analgesics; and no history or radiographic evidence of prespecified bone/joint conditions beyond OA. Patients received oral naproxen, celecoxib, or diclofenac twice daily (NSAID group; n = 996) or tanezumab 2.5 mg (n = 1,002) or 5 mg (n = 998) subcutaneously every 8 weeks. Coprimary efficacy end points at week 16 were changes in WOMAC pain and physical function scores and changes in PtGA. The primary joint safety end point over 80 weeks comprised adjudicated rapidly progressive OA type 1 or 2, primary osteonecrosis, subchondral insufficiency fracture, or pathologic fracture. Mean values, least squares mean values, and least squares mean differences between groups (with 95% confidence intervals [95% CIs]) were calculated.

Results: Of 3,021 randomized patients, 2,996 received ≥1 treatment dose. Adverse events (AEs) were similar between patients treated with tanezumab 2.5 mg and those treated with NSAIDs, and were more prevalent in those treated with tanezumab 5 mg. Composite joint safety events were significantly more prevalent with tanezumab 2.5 mg and tanezumab 5 mg than with NSAIDs (observation time-adjusted rate/1,000 patient-years 38.3 [95% CI 28.0, 52.5] and 71.5 [95% CI 56.7, 90.2], respectively, versus 14.8 [95% CI 8.9, 24.6]; P = 0.001 for tanezumab 2.5 mg versus NSAIDs; P < 0.001 for tanezumab 5 mg versus NSAIDs). Tanezumab 5 mg significantly improved pain and physical function but did not improve PtGA at week 16 when compared to NSAIDs; corresponding differences between the tanezumab 2.5 mg and NSAID groups were not statistically significant.

Conclusion: In patients previously receiving a stable dose of NSAIDs, tanezumab administered subcutaneously resulted in more joint safety events than continued NSAIDs, with differences being dose dependent. Pain and physical function improved with both doses of tanezumab compared to NSAIDs, reaching statistical significance with tanezumab 5 mg at 16 weeks.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/art.41674DOI Listing
July 2021

Neurocognitive measures predict voluntary stepping performance in older adults post-hip fracture.

Clin Biomech (Bristol, Avon) 2021 01 12;81:105234. Epub 2020 Nov 12.

University of Maryland School of Medicine, USA.

Background: Hip fracture is a debilitating injury, especially in older adults. The purpose of this study was to determine the relationships between Trail-Making test performance and parameters of the choice stepping reaction time test in community-dwelling older adults after hip fracture.

Methods: Twenty-four older adults post-hip fracture repair participated in an ancillary study for physical therapy interventions. Measures included Trail-Making test (Parts A & B) scores, movement time (time from foot liftoff to touchdown), step speed, reaction time (time from cue to foot liftoff), and total response time (time from step cue to touchdown) in the forward and lateral directions. Paired t-tests and multiple linear regressions were used for analysis.

Findings: Significant differences were found in movement time, speed and reaction time between limbs in the lateral direction, and in movement and reaction time in the forward direction. Trails A predicted step speed, reaction time and total response time for the fractured limb in the lateral direction, as well as reaction time and total response time in the forward direction. However, Trails A could not predict performance for the non-fractured limb. Trails B predicted stepping performance for both limbs in the forward and lateral directions.

Interpretation: Trails A correlated with the fractured limb's ability to perform the choice stepping test, but not in the non-fractured limb. Meanwhile, Trails B correlated with stepping performance in both limbs, suggesting those with poorer executive function have a lower protective stepping capability and may be at a higher risk for future falls and injury.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.clinbiomech.2020.105234DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8183182PMC
January 2021

Relationship Between Depression and Disease Activity in United States Veterans With Early Rheumatoid Arthritis Receiving Methotrexate.

J Rheumatol 2021 Jun 15;48(6):813-820. Epub 2020 Nov 15.

M.C.Hochberg, MD, MPH, Department of Epidemiology and Public Health, and Department of Medicine, University of Maryland Baltimore, School of Medicine, and VA Maryland Health Care System, Baltimore, Maryland, USA.

Objective: Depression is common in patients with rheumatoid arthritis (RA), exacerbates disease activity, and may decrease response to first-line disease-modifying antirheumatic drugs. This study aimed to determine if depression affects disease activity among veterans with early RA prescribed methotrexate (MTX).

Methods: Participants included veterans enrolled in the Veterans Affairs Rheumatoid Arthritis (VARA) registry with early RA (onset < 2 yrs) prescribed MTX. Depression was assessed at enrollment using the International Classification of Diseases, 9th revision codes (296.2-296.39, 300.4, 311). Disease activity was measured using the Disease Activity Score in 28 joints (DAS28) and other core measures of RA disease activity. Propensity score weights were used to adjust depressed (n = 48) and nondepressed (n = 220) patients on baseline confounders within imputed datasets. Weighted estimating equations were used to assess standardized mean differences in disease activity between depressed and nondepressed patients at 6-month, 1-year, and 2-year follow-ups.

Results: The analytic sample was composed of 268 veterans with early RA prescribed MTX who were predominantly male (n = 239, 89.2%) and older (62.7 yrs, SD 10.6) than patients with RA in the general population. Adjusted estimates indicated that depression was associated with significantly higher DAS28 at 6 months (β 0.35, 95% CI 0.01-0.68) but not at the 1- or 2-year follow-up. Also, depression was associated with significantly worse pain at 6 months (β 0.39, 95% CI 0.04-0.73) and 1 year (β 0.40, 95% CI 0.04-0.75).

Conclusion: In early RA, depression is associated with greater short-term disease activity during MTX treatment, as well as more persistent and severe pain.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3899/jrheum.200743DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8121898PMC
June 2021

Non-surgical management of knee osteoarthritis: comparison of ESCEO and OARSI 2019 guidelines.

Nat Rev Rheumatol 2021 01 28;17(1):59-66. Epub 2020 Oct 28.

WHO Collaborating Centre for Public Health Aspects of Musculoskeletal Health and Aging, Liège, Belgium.

Knee osteoarthritis (OA) is a heterogeneous disease associated with substantial effects on quality of life, and its clinical management is difficult. Among the several available guidelines for the management of knee OA, those from OARSI and ESCEO were updated in 2019. Here, we examine the similarities and differences between these two guidelines and provide a narrative to help guide health-care providers through the complexities of non-surgical management of knee OA. OARSI and ESCEO both recommend education, structured exercise and weight loss as core treatments, topical NSAIDs as first-line treatments and oral NSAIDs and intra-articular injections for persistent pain. Low-dose, short-term acetaminophen, pharmaceutical grade glucosamine and chondroitin sulfate are recommended by ESCEO whereas OARSI strongly recommends against their use (including all glucosamine and chondroitin formulations). Despite this difference, the two guidelines are consistent in the majority of their recommendations and provide useful treatment recommendations for individuals with OA and health-care providers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41584-020-00523-9DOI Listing
January 2021

Lorecivivint, an intra-articular potential disease-modifying osteoarthritis drug.

Expert Opin Investig Drugs 2020 Dec 8;29(12):1339-1346. Epub 2020 Nov 8.

Department of Medicine, Division of Rheumatology and Clinical Immunology, University of Maryland School of Medicine , Baltimore, MD, USA.

: Osteoarthritis (OA) is the most common form of arthritis. Knee OA is associated with joint pain, activity limitation, physical disability, reduced health-related quality of life, and increased mortality. To date, all pharmacologic treatments for OA are directed toward pain management. Lorecivivint (LOR) is an investigational agent that has potential as a disease-modifying osteoarthritis drug (DMOAD). It modulates the Wnt signaling pathway by inhibiting CDC-like kinase 2 and dual-specificity tyrosine phosphorylation-regulated kinase 1 A which are molecular regulators in Wnt signaling, chondrogenesis, and inflammation. : This paper discusses the current pharmacologic guidelines for the treatment of knee OA and illuminates the potential of a new agent, Lorecivivint, as a disease-modifying osteoarthritis drug (DMOAD). Efficacy and safety and the challenges for this novel agent come under the spotlight. : LOR may be a potential DMOAD for the treatment of patients with knee OA. While the Phase 2A trial did not meet its primary endpoint, preplanned analyses did identify a target population for further evaluation of its potential as a DMOAD. Phase 3 trials are ongoing, but this intra-articular drug is currently considered safe and well tolerated, with no significant reported systemic side effects.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/13543784.2020.1842357DOI Listing
December 2020

Plane Dependent Subject-Specific Neuromuscular Training for Knee Rehabilitation.

IEEE Trans Neural Syst Rehabil Eng 2020 08 26;28(8):1876-1883. Epub 2020 Jun 26.

Knee injuries at risk of post-traumatic knee osteoarthritis (PTOA) and knee osteoarthritis (OA) are closely associated with knee transverse plane and/or frontal plane instability and excessive loading. However, most existing training and rehabilitation devices involve mainly movements in the sagittal plane. An offaxis elliptical training system was developed to train and evaluate neuromuscular control about the off-axes (knee varus/valgus and tibial rotation) as well as the main flexion/extension axis (sagittal movements). Effects of the offaxis elliptical training system in improving either transverse or frontal neuromuscular control depending on subjects' need (Pivoting group, Sliding group) were demonstrated through 6-week subject-specific neuromuscular training in subjects with knee injuries at risk of PTOA or medial knee osteoarthritis. The combined pivoting and sliding group, named as offxis group demonstrated significant reduction in pivoting instability, minimum pivoting angle, and sliding instability. The pivoting group showed more reduction in pivoting instability, maximum and minimum pivoting angle than the sliding group. On the other hand, the sliding group showed more reduction in sliding instability, maximum and minimum sliding distance than the pivoting group. Based on these findings, the offaxis elliptical trainer system can potentially be used as a therapeutic and research tool to train human subjects for plane-dependent improvements in their neuromuscular control during functional weight-bearing stepping movements.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1109/TNSRE.2020.3005119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7489920PMC
August 2020

Lorecivivint, a Novel Intraarticular CDC-like Kinase 2 and Dual-Specificity Tyrosine Phosphorylation-Regulated Kinase 1A Inhibitor and Wnt Pathway Modulator for the Treatment of Knee Osteoarthritis: A Phase II Randomized Trial.

Arthritis Rheumatol 2020 10 6;72(10):1694-1706. Epub 2020 Sep 6.

University of Maryland School of Medicine, Baltimore, Maryland.

Objective: To assess the safety and efficacy of a novel Wnt pathway modulator, lorecivivint (SM04690), for treating pain and inhibiting structural progression in moderately to severely symptomatic knee osteoarthritis (OA).

Methods: Subjects in this 52-week, phase IIa, multicenter, randomized, double-blind, placebo-controlled, dose-ranging trial received a single 2-ml intraarticular injection of lorecivivint (dose of 0.03 mg, 0.07 mg, or 0.23 mg) or placebo. Efficacy was assessed based on change from baseline on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score subscales for pain and function (scale 0-100 for each) and change from baseline in the radiographic medial joint space width (JSW). Baseline-adjusted analysis of covariance with multiple imputation was performed separately to evaluate efficacy. This proof-of-concept study evaluated the intent-to-treat population as well as a prespecified group of subjects with unilateral symptoms of knee OA (designated UNI) and an additional post hoc subgroup of subjects with unilateral symptoms but without widespread pain (designated UNI WP-).

Results: In this trial, 455 subjects were randomized to a treatment group. The primary end point, significant improvement in the WOMAC pain score compared with placebo at week 13, was not met by any lorecivivint dose group (mean ± SD change from baseline, -23.3 ± 2.2 in the 0.03 mg group, -23.5 ± 2.1 in the 0.07 mg group, -21.3 ± 2.2 in the 0.23 mg group, and -22.1 ± 2.1 in the placebo group; each P > 0.05 versus placebo). All groups (including placebo) demonstrated clinically meaningful (≥20-point) improvements from baseline in the WOMAC pain score. The durability of response was evaluated through week 52. In the prespecified UNI group and post hoc UNI WP- group at week 52, treatment with 0.07 mg lorecivivint significantly improved the WOMAC pain score (between-group difference versus placebo, -8.73, 95% confidence interval [95% CI] -17.44, -0.03 [P = 0.049] and -11.21, 95% CI -20.99, -1.43 [P = 0.025], respectively) and WOMAC function score (between-group difference versus placebo, -10.26, 95% CI -19.82, -0.69 [P = 0.036] and -13.38, 95% CI -24.33, -2.43 [P = 0.017], respectively). Relative to baseline, the mean change in the medial JSW at week 52 was -0.04 mm in the 0.03 mg cohort, -0.09 mm in the 0.07 mg cohort, -0.16 mm in the 0.23 mg cohort, and -0.14 mm in the placebo cohort; no treatment group achieved a significant change in medial JSW compared with placebo at week 52. In both unilateral symptom subgroups, the 0.07 mg lorecivivint dose significantly increased medial JSW compared with placebo at week 52 (medial JSW 0.39 mm, 95% CI 0.06, 0.72 in the UNI group [P = 0.021] and 0.42 mm, 95% CI 0.04, 0.80 in the UNI WP- group [P = 0.032]). Changes observed in the 0.03 mg and 0.23 mg dose groups were not significantly different from those in the placebo group for any of these measures. Lorecivivint appeared safe and well tolerated.

Conclusion: This phase IIa, proof-of-concept trial in patients with symptomatic knee OA did not meet its primary end point. Nevertheless, the study identified a target population in whom to evaluate the potential efficacy of lorecivivint for the treatment of knee OA.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/art.41315DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7589351PMC
October 2020

Association between disease progression and depression onset in persons with radiographic knee osteoarthritis.

Rheumatology (Oxford) 2020 11;59(11):3390-3399

Department of Medicine, University of Maryland School of Medicine, Baltimore, MD.

Objectives: Osteoarthritis (OA) disease progression may lead to deteriorating psychosocial function, but it is unclear what aspects of disease severity are related to the onset of depression. This study assessed which components of OA disease progression cumulatively contribute to depression onset in persons with radiographic knee OA.

Methods: Osteoarthritis Initiative participants (n = 1651) with radiographic disease (Kellgren-Lawrence grade ≥2) in one or both knees and below the screening threshold for probable depression [Center for Epidemiological Studies Depression (CES-D) scale <16] at baseline were included. Disease severity was measured from baseline to the third annual follow-up visit using joint space width, 20-meter gait speed, and the Western Ontario and McMaster Universities Osteoarthritis Index pain subscale, each categorized into quintiles. Depression onset (CES-D ≥ 16) was assessed annually at four follow-up visits. Marginal structural models that account for time-dependent confounding and attrition evaluated the association between each time-varying disease severity measure and depression onset.

Results: Each disease severity measure exhibited a non-linear relationship concerning the probability of depression onset, with the higher quintiles generally being associated with a larger risk. The highest quintile (relative to the lowest) of joint space width and gait speed were both significantly associated with depression onset. By contrast, none of the higher pain quintiles compared with the lowest were significantly associated with the onset of depression.

Conclusion: Faster disease progression as measured by either worsening structural severity or decreasing physical performance corresponds to an increased risk of depression among individuals with radiographic knee OA.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/rheumatology/keaa141DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7590406PMC
November 2020

Comparing Longitudinal Sarcopenia Trends by Definitions Across Men and Women After Hip Fracture.

J Am Geriatr Soc 2020 07 1;68(7):1537-1544. Epub 2020 Apr 1.

Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, Maryland, USA.

Objectives: While sarcopenia is prevalent after hip fracture in the acute postfracture period, little is known about the prevalence after discharge. This study assessed longitudinal trends in sarcopenia prevalence over 12 months after hip fracture using three different operational definitions.

Design: Prospective observational study.

Setting: Baltimore Hip Studies seventh cohort.

Participants: A total of 82 men and 78 women, aged 65 years and older, with surgical repair of a nonpathological hip fracture.

Measurements: Baseline assessment included a dual-energy X-ray absorptiometry scan and interview. Follow-up assessments, which additionally included performance measures, occurred 2, 6, and 12 months after admission. Using these measures, three sarcopenia definitions were assessed over the year following hip fracture: European Working Group on Sarcopenia in Older Persons (EWGSOP), International Working Group on Sarcopenia (IWGS), and Foundation for the National Institutes of Health (FNIH).

Results: EWGSOP and IWGS provided the highest prevalence of sarcopenia (62%-69% in men, 42%-62% in women), while prevalence by FNIH was much lower for men (15%-19%) and women (5%-12%). For both men and women, the agreement between EWGSOP and IWGS definitions was excellent, and FNIH showed poor agreement with them, supported by various statistical measures across first-year follow-up. Prevalence was stable over time in men by all definitions, while the prevalence in women by FNIH was lowest at 2 months, significantly increased at 6 months (P = .03), and remained higher at 12 months. Whether sarcopenia prevalence differed significantly by sex varied by time point and definition; however, when different, men had a higher prevalence than women (P < .05). While some participants recovered from sarcopenia over time, some also became newly sarcopenic.

Conclusion: The prevalence of sarcopenia after fracture differed greatly for EWGSOP and IWGS compared to FNIH. Overall, there appeared to be no reduction in sarcopenia over the year after hip fracture, regardless of definition. Future research should examine the relationship between sarcopenia prevalence and functional recovery. J Am Geriatr Soc 68:1537-1544, 2020.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jgs.16417DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7416476PMC
July 2020

Secondary Fracture Prevention: Consensus Clinical Recommendations from a Multistakeholder Coalition.

J Orthop Trauma 2020 Apr;34(4):e125-e141

Mary MacKillop Institute for Health Research, Australian Catholic University, Melbourne, Victoria, Australia.

Osteoporosis-related fractures are undertreated, due in part to misinformation about recommended approaches to patient care and discrepancies among treatment guidelines. To help bridge this gap and improve patient outcomes, the American Society for Bone and Mineral Research assembled a multistakeholder coalition to develop clinical recommendations for the optimal prevention of secondary fractureamong people aged 65 years and older with a hip or vertebral fracture. The coalition developed 13 recommendations (7 primary and 6 secondary) strongly supported by the empirical literature. The coalition recommends increased communication with patients regarding fracture risk, mortality and morbidity outcomes, and fracture risk reduction. Risk assessment (including fall history) should occur at regular intervals with referral to physical and/or occupational therapy as appropriate. Oral, intravenous, andsubcutaneous pharmacotherapies are efficaciousandcanreduce risk of future fracture.Patientsneededucation,however, about thebenefitsandrisks of both treatment and not receiving treatment. Oral bisphosphonates alendronate and risedronate are first-line options and are generally well tolerated; otherwise, intravenous zoledronic acid and subcutaneous denosumab can be considered. Anabolic agents are expensive butmay be beneficial for selected patients at high risk.Optimal duration of pharmacotherapy is unknown but because the risk for second fractures is highest in the earlypost-fractureperiod,prompt treatment is recommended.Adequate dietary or supplemental vitaminDand calciumintake shouldbe assured. Individuals beingtreatedfor osteoporosis shouldbe reevaluated for fracture risk routinely, includingvia patienteducationabout osteoporosisandfracturesandmonitoringfor adverse treatment effects.Patients shouldbestronglyencouraged to avoid tobacco, consume alcohol inmoderation atmost, and engage in regular exercise and fall prevention strategies. Finally, referral to endocrinologists or other osteoporosis specialists may be warranted for individuals who experience repeated fracture or bone loss and those with complicating comorbidities (eg, hyperparathyroidism, chronic kidney disease).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/BOT.0000000000001743DOI Listing
April 2020

Genome-wide meta-analysis identified novel variant associated with hallux valgus in Caucasians.

J Foot Ankle Res 2020 Mar 4;13(1):11. Epub 2020 Mar 4.

University of Maryland School of Medicine, Baltimore, MD, USA.

Background: Hallux valgus, one of the most common structural foot deformities, is highly heritable. However, previous efforts to elucidate the genetic underpinnings of hallux valgus through a genome-wide association study (GWAS) conducted in 4409 Caucasians did not identify genome-wide significant associations with hallux valgus in both gender-specific and sex-combined GWAS meta-analyses. In this analysis, we add newly available data and more densely imputed genotypes to identify novel genetic variants associated with hallux valgus.

Methods: A total of 5925 individuals of European Ancestry were categorized into two groups: 'hallux valgus present' (n = 2314) or 'no deformity' (n = 3611) as determined by trained examiners or using the Manchester grading scale. Genotyping was performed using commercially available arrays followed by imputation to the Haplotype Reference Consortium (HRC) reference panel version 1.1. We conducted both sex-specific and sex-combined association analyses using logistic regression and generalized estimating equations as appropriate in each cohort. Results were then combined in a fixed-effects inverse-variance meta-analyses. Functional Mapping and Annotation web-based platform (FUMA) was used for positional mapping, gene and gene-set analyses.

Results: We identified a novel locus in the intronic region of CLCA2 on chromosome 1, rs55807512 (OR = 0.48, p = 2.96E-09), an expression quantitative trait locus for COL24A1, a member of the collagen gene family.

Conclusion: In this report of the largest GWAS of hallux valgus to date, we identified a novel genome-wide significant locus for hallux valgus. Additional replication and functional follow-up will be needed to determine the functional role of this locus in hallux valgus biology.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13047-020-0379-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7057609PMC
March 2020

Intra-articular sprifermin reduces cartilage loss in addition to increasing cartilage gain independent of location in the femorotibial joint: post-hoc analysis of a randomised, placebo-controlled phase II clinical trial.

Ann Rheum Dis 2020 04 25;79(4):525-528. Epub 2020 Feb 25.

University of Maryland School of Medicine, Baltimore, Maryland, USA.

Objectives: In the phase II FGF-18 Osteoarthritis Randomized Trial with Administration of Repeated Doses (FORWARD) study, sprifermin demonstrated cartilage modification in the total femorotibial joint and in both femorotibial compartments by MRI in patients with knee osteoarthritis. Here, we evaluate whether sprifermin reduces cartilage loss and increases cartilage thickness, independent of location.

Methods: Patients were randomised 1:1:1:1:1 to three once-weekly intra-articular injections of 30 µg sprifermin every 6 months (q6mo); 30 µg sprifermin every 12 months (q12mo); 100 µg sprifermin q6mo; 100 µg sprifermin q12mo; or placebo. Post-hoc analysis using thinning/thickening scores and ordered values evaluated femorotibial cartilage thickness change from baseline to 24 months independent of location. Changes were indirectly compared with those of Osteoarthritis Initiative healthy subjects.

Results: Thinning scores were significantly lower for sprifermin 100 µg q6mo versus placebo (mean (95% CI) difference: 334 µm (114 to 554)), with a cartilage thinning score similar to healthy subjects. Thickening scores were significantly greater for sprifermin 100 µg q6mo, 100 µg q12mo and 30 µg q6mo versus placebo (mean (95% CI) difference: 425 µm (267 to 584); 450 µm (305 to 594) and 139 µm (19 to 259), respectively) and more than doubled versus healthy subjects.

Conclusions: Sprifermin increases cartilage thickness, and substantially reduces cartilage loss, expanding FORWARD primary results.

Trial Registration Number: NCT01919164.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/annrheumdis-2019-216453DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7147175PMC
April 2020

Intra-articular Corticosteroid Injections in the Hip and Knee: Perhaps Not as Dangerous as They Want You to Believe?

Radiology 2020 04 25;295(1):249-250. Epub 2020 Feb 25.

Division of Rheumatology, Allergy, & Immunology, Tufts Medical Center, 35 Kneeland St, 4th Floor, Boston, MA 02115.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1148/radiol.2020200050DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7104696PMC
April 2020

2019 American College of Rheumatology/Arthritis Foundation Guideline for the Management of Osteoarthritis of the Hand, Hip, and Knee.

Arthritis Rheumatol 2020 02 6;72(2):220-233. Epub 2020 Jan 6.

American College of Rheumatology, Atlanta, Georgia.

Objective: To develop an evidence-based guideline for the comprehensive management of osteoarthritis (OA) as a collaboration between the American College of Rheumatology (ACR) and the Arthritis Foundation, updating the 2012 ACR recommendations for the management of hand, hip, and knee OA.

Methods: We identified clinically relevant population, intervention, comparator, outcomes questions and critical outcomes in OA. A Literature Review Team performed a systematic literature review to summarize evidence supporting the benefits and harms of available educational, behavioral, psychosocial, physical, mind-body, and pharmacologic therapies for OA. Grading of Recommendations Assessment, Development and Evaluation methodology was used to rate the quality of the evidence. A Voting Panel, including rheumatologists, an internist, physical and occupational therapists, and patients, achieved consensus on the recommendations.

Results: Based on the available evidence, either strong or conditional recommendations were made for or against the approaches evaluated. Strong recommendations were made for exercise, weight loss in patients with knee and/or hip OA who are overweight or obese, self-efficacy and self-management programs, tai chi, cane use, hand orthoses for first carpometacarpal (CMC) joint OA, tibiofemoral bracing for tibiofemoral knee OA, topical nonsteroidal antiinflammatory drugs (NSAIDs) for knee OA, oral NSAIDs, and intraarticular glucocorticoid injections for knee OA. Conditional recommendations were made for balance exercises, yoga, cognitive behavioral therapy, kinesiotaping for first CMC OA, orthoses for hand joints other than the first CMC joint, patellofemoral bracing for patellofemoral knee OA, acupuncture, thermal modalities, radiofrequency ablation for knee OA, topical NSAIDs, intraarticular steroid injections and chondroitin sulfate for hand OA, topical capsaicin for knee OA, acetaminophen, duloxetine, and tramadol.

Conclusion: This guideline provides direction for clinicians and patients making treatment decisions for the management of OA. Clinicians and patients should engage in shared decision-making that accounts for patients' values, preferences, and comorbidities. These recommendations should not be used to limit or deny access to therapies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/art.41142DOI Listing
February 2020

2019 American College of Rheumatology/Arthritis Foundation Guideline for the Management of Osteoarthritis of the Hand, Hip, and Knee.

Arthritis Care Res (Hoboken) 2020 02 6;72(2):149-162. Epub 2020 Jan 6.

American College of Rheumatology, Atlanta, Georgia.

Objective: To develop an evidence-based guideline for the comprehensive management of osteoarthritis (OA) as a collaboration between the American College of Rheumatology (ACR) and the Arthritis Foundation, updating the 2012 ACR recommendations for the management of hand, hip, and knee OA.

Methods: We identified clinically relevant population, intervention, comparator, outcomes questions and critical outcomes in OA. A Literature Review Team performed a systematic literature review to summarize evidence supporting the benefits and harms of available educational, behavioral, psychosocial, physical, mind-body, and pharmacologic therapies for OA. Grading of Recommendations Assessment, Development and Evaluation methodology was used to rate the quality of the evidence. A Voting Panel, including rheumatologists, an internist, physical and occupational therapists, and patients, achieved consensus on the recommendations.

Results: Based on the available evidence, either strong or conditional recommendations were made for or against the approaches evaluated. Strong recommendations were made for exercise, weight loss in patients with knee and/or hip OA who are overweight or obese, self-efficacy and self-management programs, tai chi, cane use, hand orthoses for first carpometacarpal (CMC) joint OA, tibiofemoral bracing for tibiofemoral knee OA, topical nonsteroidal antiinflammatory drugs (NSAIDs) for knee OA, oral NSAIDs, and intraarticular glucocorticoid injections for knee OA. Conditional recommendations were made for balance exercises, yoga, cognitive behavioral therapy, kinesiotaping for first CMC OA, orthoses for hand joints other than the first CMC joint, patellofemoral bracing for patellofemoral knee OA, acupuncture, thermal modalities, radiofrequency ablation for knee OA, topical NSAIDs, intraarticular steroid injections and chondroitin sulfate for hand OA, topical capsaicin for knee OA, acetaminophen, duloxetine, and tramadol.

Conclusion: This guideline provides direction for clinicians and patients making treatment decisions for the management of OA. Clinicians and patients should engage in shared decision-making that accounts for patients' values, preferences, and comorbidities. These recommendations should not be used to limit or deny access to therapies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/acr.24131DOI Listing
February 2020

Interleukin 1 receptor antagonist () gene variants predict radiographic severity of knee osteoarthritis and risk of incident disease.

Ann Rheum Dis 2020 03 18;79(3):400-407. Epub 2019 Dec 18.

Department of Medicine, Division of Rheumatology, New York University School of Medicine, New York, New York, USA

Objective: In these studies, we examined the association of single nucleotide polymorphisms (SNPs) of the gene with radiographic severity of symptomatic knee osteoarthritis (SKOA) and the risk of incident OA. We also explored these genetic polymorphisms in patients with new onset rheumatoid arthritis (RA).

Methods: Over 1000 subjects who met American College of Rheumatology criteria for tibiofemoral OA were selected from three independent, National Institute of Health (NIH)-funded cohorts. CTA and TTG haplotypes formed from three SNPs of the gene (rs419598, rs315952, rs9005) were assessed for association with radiographic severity, and risk for incident radiographic OA (rOA) in a nested case-control cohort. These haplotypes were also assessed for association with disease activity (DAS28) and plasma inflammatory markers in patients with RA.

Results: Carriage of the TTG haplotype was associated with increased odds of more severe rOA compared with age-matched, sex-matched and body mass index-matched individuals. Examination of the osteoarthritis initiative demonstrated that carriage of the TTG haplotype was associated with 4.1-fold (p=0.001) increased odds of incident rOA. Plasma IL-1Ra levels were lower in TTG carriers, while chondrocytes from TTG carriers exhibited decreased secretion of IL-1Ra. In patients with RA, the TTG haplotype was associated with increased DAS28, decreased plasma IL-1Ra and elevations of plasma inflammatory markers (hsCRP, interleukin 6 (IL-6)).

Conclusion: Carriage of the TTG haplotype is associated with more severe rOA, increased risk for incident OA, and increased evidence of inflammation in RA. These data suggest that the TTG risk haplotype, associated with decreased IL-1Ra plasma levels, impairs endogenous 'anti-inflammatory' mechanisms.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/annrheumdis-2019-216055DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7034355PMC
March 2020

Differences in geometric strength at the contralateral hip between men with hip fracture and non-fractured comparators.

Bone 2020 03 5;132:115187. Epub 2019 Dec 5.

University of Maryland School of Medicine, Baltimore, MD, USA; VA Maryland Health Care System, Baltimore, MD, USA.

Older men sustain excess bone mineral density (BMD) declines after hip fracture; however, BMD provides no information on mechanical structure and strength. The aim was to assess whether changes in hip bone geometry in older men after hip fracture differ than that expected with aging. Two cohorts were used: Baltimore Hip Studies 7th cohort (BHS-7) and Baltimore Men's Osteoporosis Study (MOST). The sample (N = 170) included older Caucasian men with hip fracture that were propensity score matched (1:1) to community-dwelling non-fractured comparators. Hip Structural Analysis (HSA) calculated aerial BMD and metrics of bone structural strength: cross-sectional bone area (CSA), cortical outer diameter (OD), section modulus (SM), and centroid position (CP). Mixed-effect models estimated changes in HSA parameters and adjusted robust regression models evaluated between-cohort differences in annual percent change at the narrow neck (NN), intertrochanteric (IT), and femoral shaft (FS). Hip fracture was associated with statistically greater declines in NN CSA (β = -2.818; 95% CI: -3.300%, -2.336%), SM (β = -1.896%; 95% CI: -2.711%, -1.080%) and CP (β = -0.884%; 95% CI: -0.889%, -0.880%) and significantly larger increases in NN OD (β = 0.187%; 95% CI: 0.185%, 0.190%). Differences in IT HSA parameters were like the NN but larger in magnitude, while there were favorable changes in FS geometry where fragility fractures are rare. Findings indicate there are declines in bone structure and strength at the NN and IT regions of the proximal femur in older men during hip fracture recovery that far exceed what occurs during normal aging.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bone.2019.115187DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7037571PMC
March 2020

Safety of Abatacept Versus Placebo in Rheumatoid Arthritis: Integrated Data Analysis of Nine Clinical Trials.

ACR Open Rheumatol 2019 Jun 29;1(4):251-257. Epub 2019 May 29.

Amsterdam University Medical Centers Vrije Universiteit Amsterdam Netherlands.

Objective: To assess the safety of abatacept treatment in rheumatoid arthritis (RA) using integrated data from multiple clinical trials.

Methods: Data from nine double-blind, placebo-controlled studies of abatacept treatment (seven intravenous, two subcutaneous) in patients with RA were pooled, focusing on safety events in the double-blind treatment period of each study. Incidence rates (IRs) of adverse events (AEs) per 100 patient-years of exposure were calculated for abatacept- and placebo-treated patients. AEs in abatacept-treated patients were combined regardless of dose and formulation.

Results: In total, 2653 patients received abatacept and 1485 received placebo, with 2357 and 1254 patient-years of exposure, respectively. The mean (SD) durations of exposure in the abatacept and placebo groups were 10.8 (3.3) and 10.3 (3.5) months, respectively. The IRs (95% confidence interval [CI]) for serious AEs were 14.8 (13.3, 16.5) and 14.6 (12.5, 17.0) in the abatacept and placebo groups, respectively. Death occurred in 12 (0.5%) and 12 (0.8%) patients in the abatacept and placebo groups, respectively, and was most commonly caused by cardiac disorders. Malignancies were observed in 31 patients (1.2%) treated with abatacept (IR: 1.32 [95% CI: 0.90, 1.87]) versus 14 (0.9%; IR: 1.12 [0.61, 1.88]) who received placebo. Solid organ tumor was the most frequent malignancy reported in both groups (abatacept: 1.0%; IR: 1.11 [95% CI: 0.72, 1.62]; placebo: 0.8%; 0.96 [0.50, 1.67]).

Conclusion: In this integrated analysis, the IRs of safety events in the abatacept and placebo groups were similar with no new safety concerns identified.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/acr2.1034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6858048PMC
June 2019

Comparative risk of malignancies and infections in patients with rheumatoid arthritis initiating abatacept versus other biologics: a multi-database real-world study.

Arthritis Res Ther 2019 11 8;21(1):228. Epub 2019 Nov 8.

Bristol-Myers Squibb, Princeton, NJ, USA.

Background: Patients with rheumatoid arthritis (RA) are at an increased risk of developing certain cancers and infections compared with the general population. Biologic and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) are effective treatment options for RA, but limited evidence is available on the comparative risks among b/tsDMARDs. We assessed the risk of malignancies and infections in patients with RA who initiated abatacept versus other b/tsDMARDs in a real-world setting.

Methods: This retrospective, observational study used administrative data from three large US healthcare databases (MarketScan, PharMetrics, and Optum) to identify patients treated with abatacept or other b/tsDMARDs. In both groups, age-stratified incidence rates (IRs) with 95% confidence intervals (CIs) were calculated for total malignancy and hospitalized infections; propensity score matching and Cox proportional hazards regression models were used to estimate hazard ratios (HRs) with 95% CIs for total malignancy, lung cancer, lymphoma, breast cancer, non-melanoma skin cancer (NMSC), hospitalized infections, opportunistic infections, and tuberculosis (TB), both within individual databases and in meta-analyses across the three databases.

Results: A rounded total of 19.2, 13.6, and 4.2 thousand patients initiating abatacept and 55.3, 40.8, and 13.8 thousand initiating other b/tsDMARDs were identified in the MarketScan, PharMetrics, and Optum databases, respectively. The IRs for total malignancy and hospitalized infections were similar between the two groups in each age stratum. In meta-analyses, total malignancy risk (HR [95% CI] 1.09 [1.02-1.16]) of abatacept versus other b/tsDMARDs was slightly but statistically significantly increased; small, but not statistically significant, increases were seen for lung cancer (1.10 [0.62-1.96]), lymphoma (1.27 [0.94-1.72]), breast cancer (1.15 [0.92-1.45]), and NMSC (1.10 [0.93-1.30]). No significant increase in hospitalized infections (0.96 [0.84-1.09]) or opportunistic infections (1.06 [0.96-1.17]) was seen. For TB, low event counts precluded meta-analysis.

Conclusions: In this real-world multi-database study, the risks for specific cancers and infections did not differ significantly between patients in the abatacept and other b/tsDMARDs groups. The slight increase in total malignancy risk associated with abatacept needs further investigation. These results are consistent with the established safety profile of abatacept.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13075-019-1992-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6839238PMC
November 2019

Football Increases Future Risk of Symptomatic Radiographic Knee Osteoarthritis.

Med Sci Sports Exerc 2020 04;52(4):795-800

Division of Rheumatology, Tufts Medical Center, Boston, MA.

Introduction: Male youth in the United States commonly participate in gridiron (American) football. There are little data substantiating current popular opinion that it is associated with knee pain or osteoarthritis (OA) later in life. We aimed to evaluate the relationship of football with these outcomes in the Osteoarthritis Initiative (OAI).

Methods: This is a study of male OAI participants with knee x-ray readings, symptom assessments, and completed surveys on lifetime physical activity. The OAI is a multicenter, observational cohort recruited from the community not based on football participation status. A history of exposure to American football was ascertained via self-report. Knee radiographs were scored for Kellgren-Lawrence grade (0-4). Radiographic OA (ROA) was defined as Kellgren-Lawrence ≥ 2 in at least one knee. Frequent knee pain meant at least one knee with frequent knee pain. Symptomatic ROA required at least one knee with both ROA and frequent knee pain.

Results: A total of 1166 men had a mean age of 63.7 (SD, 9.2) yr and body mass index of 28.6 (SD, 4.2) kg·m. Thirty-one percent (365/1166) played football at some point in their lives, 95% of whom participated from ages 12 to 18 yr. The ORs for symptomatic ROA from the lowest to highest football participation were 1.2, 1.5, and 2.2, respectively (P for trend = 0.004). Findings were similar for football from ages 12 to 18 yr and for outcomes of knee pain and ROA.

Conclusion: This is the first large epidemiologic study to suggest that football participation, including in the teen years, may be detrimental toward knee health. Prospective studies evaluating football players are warranted.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1249/MSS.0000000000002189DOI Listing
April 2020

Evidence that Swimming May Be Protective of Knee Osteoarthritis: Data from the Osteoarthritis Initiative.

PM R 2020 06 4;12(6):529-537. Epub 2019 Dec 4.

Department of General Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX.

Background: To date, there have not been any epidemiologic studies that have evaluated the association between swimming over a lifetime and knee health.

Objective: The study aimed to evaluate the relationship of a history of swimming with knee pain, radiographic knee OA (ROA), and symptomatic knee OA (SOA).

Design: Cross-sectional retrospective study.

Setting: Four academic centers in the United States.

Participants: Respondents to the historical physical activity survey within the Osteoarthritis Initiative with knee radiographs and symptom assessments.

Methods: In this retrospective study nested within the Osteoarthritis Initiative, researchers performed logistic regression with the predictor being swimming over a lifetime and over particular age ranges.

Main Outcome Measurements: Person-based definitions of frequent knee pain, ROA, and SOA.

Results: A total of 2637 participants were included, with a mean age of 64.3 years (SD 8.9), body mass index of 28.4 kg/m (SD 4.9), and 44.2% male. Over a lifetime, the adjusted prevalence measures for frequent knee pain, ROA, and SOA for any versus no history of swimming were 36.4% (33.4% - 39.5%) v. 39.9% (37.4% - 42.5%), 54.3% (51.0% - 57.6%) v. 61.1% (58.4% - 63.7%), and 21.9% (19.4% - 24.7%) v. 27.0% (24.7% - 29.4%) respectively.

Conclusions: This is the first epidemiologic study to indicate that swimming is potentially beneficial toward knee health, particularly when performed earlier in life (before age 35). Future prospective studies are needed to confirm these findings and to better scrutinize the associations in older age groups.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/pmrj.12267DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7166141PMC
June 2020

Effect of Intra-Articular Sprifermin vs Placebo on Femorotibial Joint Cartilage Thickness in Patients With Osteoarthritis: The FORWARD Randomized Clinical Trial.

JAMA 2019 10;322(14):1360-1370

Institute of Anatomy, Department of Imaging and Functional Musculoskeletal Research, Paracelsus Medical University Salzburg and Nuremberg, Salzburg, Austria.

Importance: Sprifermin is under investigation as a disease-modifying osteoarthritis drug.

Objective: To evaluate the effects of sprifermin on changes in total femorotibial joint cartilage thickness in the more symptomatic knee of patients with osteoarthritis.

Design, Setting, And Participants: FORWARD (FGF-18 Osteoarthritis Randomized Trial with Administration of Repeated Doses) was a 5-year, dose-finding, multicenter randomized clinical trial conducted at 10 sites. Eligible participants were aged 40 to 85 years with symptomatic, radiographic knee osteoarthritis and Kellgren-Lawrence grade 2 or 3. Enrollment began in July 2013 and ended in May 2014; the last participant visit occurred on May 8, 2017. The primary outcome at 2 years and a follow-up analysis at 3 years are reported.

Interventions: Participants were randomized to 1 of 5 groups: intra-articular injections of 100 μg of sprifermin administered every 6 months (n = 110) or every 12 months (n = 110), 30 μg of sprifermin every 6 months (n = 111) or every 12 months (n = 110), or placebo every 6 months (n = 108). Each treatment consisted of weekly injections over 3 weeks.

Main Outcomes And Measures: The primary end point was change in total femorotibial joint cartilage thickness measured by quantitative magnetic resonance imaging at 2 years. The secondary end points (of 15 total) included 2-year change from baseline in total Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores. The minimal clinically important difference (MCID) is unknown for the primary outcome; for total WOMAC score in patients with hip and knee osteoarthritis, the absolute MCID is 7 U (95% CI, 4 to 10 U) and the percentage MCID is 14% (95% CI, 9% to 18%).

Results: Among 549 participants (median age, 65.0 years; 379 female [69.0%]), 474 (86.3%) completed 2-year follow-up. Compared with placebo, the changes from baseline to 2 years in total femorotibial joint cartilage thickness were 0.05 mm (95% CI, 0.03 to 0.07 mm) for 100 μg of sprifermin administered every 6 months; 0.04 mm (95% CI, 0.02 to 0.06 mm) for 100 μg of sprifermin every 12 months; 0.02 mm (95% CI, -0.01 to 0.04 mm) for 30 μg of sprifermin every 6 months; and 0.01 mm (95% CI, -0.01 to 0.03 mm) for 30 μg of sprifermin every 12 months. Compared with placebo, there were no statistically significant differences in mean absolute change from baseline in total WOMAC scores for 100 μg of sprifermin administered every 6 months or every 12 months, or for 30 μg of sprifermin every 6 months or every 12 months. The most frequently reported treatment-emergent adverse event was arthralgia (placebo: n = 46 [43.0%]; 100 μg of sprifermin administered every 6 months: n = 45 [41.3%]; 100 μg of sprifermin every 12 months: n = 50 [45.0%]; 30 μg of sprifermin every 6 months: n = 40 [36.0%]; and 30 μg of sprifermin every 12 months: n = 48 [44.0%]).

Conclusions And Relevance: Among participants with symptomatic radiographic knee osteoarthritis, the intra-articular administration of 100 μg of sprifermin every 6 or 12 months vs placebo resulted in an improvement in total femorotibial joint cartilage thickness after 2 years that was statistically significant, but of uncertain clinical importance; there was no significant difference for 30 μg of sprifermin every 6 or 12 months vs placebo. Durability of response also was uncertain.

Trial Registration: ClinicalTrials.gov Identifier: NCT01919164.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jama.2019.14735DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6784851PMC
October 2019
-->