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- Emery, Carolyn A, et al.
(författare)
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Establishing outcome measures in early knee osteoarthritis
- 2019
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Ingår i: Nature Reviews Rheumatology. - : Springer Science and Business Media LLC. - 1759-4804 .- 1759-4790. ; 15:7, s. 438-448
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Forskningsöversikt (refereegranskat)abstract
- The classification and monitoring of individuals with early knee osteoarthritis (OA) are important considerations for the design and evaluation of therapeutic interventions and require the identification of appropriate outcome measures. Potential outcome domains to assess for early OA include patient-reported outcomes (such as pain, function and quality of life), features of clinical examination (such as joint line tenderness and crepitus), objective measures of physical function, levels of physical activity, features of imaging modalities (such as of magnetic resonance imaging) and biochemical markers in body fluid. Patient characteristics such as adiposity and biomechanics of the knee could also have relevance to the assessment of early OA. Importantly, research is needed to enable the selection of outcome measures that are feasible, reliable and validated in individuals at risk of knee OA or with early knee OA. In this Perspectives article, potential outcome measures for early symptomatic knee OA are discussed, including those measures that could be of use in clinical practice and/or the research setting.
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- Johansson, Fredrik, 1988, et al.
(författare)
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Predicting response to tocilizumab monotherapy in rheumatoid arthritis: A real-world data analysis using machine learning
- 2021
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Ingår i: Journal of Rheumatology. - : The Journal of Rheumatology. - 1499-2752 .- 0315-162X. ; 48:9, s. 1364-1370
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Tidskriftsartikel (refereegranskat)abstract
- Objective. Tocilizumab (TCZ) has shown similar efficacy when used as monotherapy as in combination with other treatments for rheumatoid arthritis (RA) in randomized controlled trials (RCTs). We derived a remission prediction score for TCZ monotherapy (TCZm) using RCT data and performed an external validation of the prediction score using real-world data (RWD). Methods. We identified patients in the Corrona RA registry who used TCZm (n = 452), and matched the design and patients from 4 RCTs used in previous work (n = 853). Patients were followed to determine remission status at 24 weeks. We compared the performance of remission prediction models in RWD, first based on variables determined in our prior work in RCTs, and then using an extended variable set, comparing logistic regression and random forest models. We included patients on other biologic disease-modifying antirheumatic drug monotherapies (bDMARDm) to improve prediction. Results. The fraction of patients observed reaching remission on TCZm by their follow-up visit was 12% (n = 53) in RWD vs 15% (n = 127) in RCTs. Discrimination was good in RWD for the risk score developed in RCTs, with area under the receiver-operating characteristic curve (AUROC) of 0.69 (95% CI 0.62-0.75). Fitting the same logistic regression model to all bDMARDm patients in the RWD improved the AUROC on held-out TCZm patients to 0.72 (95% CI 0.63-0.81). Extending the variable set and adding regularization further increased it to 0.76 (95% CI 0.67-0.84). Conclusion. The remission prediction scores, derived in RCTs, discriminated patients in RWD about as well as in RCTs. Discrimination was further improved by retraining models on RWD.
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- Solomon, Daniel H., et al.
(författare)
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The sequence of disease-modifying anti-rheumatic drugs: pathways to and predictors of tocilizumab monotherapy
- 2021
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Ingår i: Arthritis Research and Therapy. - : Springer Science and Business Media LLC. - 1478-6362 .- 1478-6354. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: There are numerous non-biologic and biologic disease-modifying anti-rheumatic drugs (bDMARDs) for rheumatoid arthritis (RA). Typical sequences of bDMARDs are not clear. Future treatment policies and trials should be informed by quantitative estimates of current treatment practice. Methods: We used data from Corrona, a large real-world RA registry, to develop a method for quantifying sequential patterns in treatment with bDMARDs. As a proof of concept, we study patients who eventually use tocilizumab monotherapy (TCZm), an IL-6 antagonist with similar benefits used as monotherapy or in combination. Patients starting a bDMARD were included and were followed using a discrete-state Markov model, observing changes in treatments every 6 months and determining whether they used TCZm. A supervised machine learning algorithm was then employed to determine longitudinal patient factors associated with TCZm use. Results: 7300 patients starting a bDMARD were followed for up to 5 years. Their median age was 58 years, 78% were female, median disease duration was 5 years, and 57% were seropositive. During follow-up, 287 (3.9%) reported use of TCZm with median time until use of 25.6 (11.5, 56.0) months. Eighty-two percent of TCZm use began within 3 years of starting any bDMARD. Ninety-three percent of TCZm users switched from TCZ combination, a TNF inhibitor, or another bDMARD. Very few patients are given TCZm as their first DMARD (0.6%). Variables associated with the use of TCZm included prior use of TCZ combination therapy, older age, longer disease duration, seronegative, higher disease activity, and no prior use of a TNF inhibitor. Conclusions: Improved understanding of treatment sequences in RA may help personalize care. These methods may help optimize treatment decisions using large-scale real-world data.
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- Suter, Lisa G., et al.
(författare)
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Projecting Lifetime Risk of Symptomatic Knee Osteoarthritis and Total Knee Replacement in Individuals Sustaining a Complete Anterior Cruciate Ligament Tear in Early Adulthood
- 2017
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Ingår i: Arthritis Care and Research. - : Wiley. - 2151-464X. ; 69:2, s. 201-208
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To estimate the lifetime risk of knee osteoarthritis (OA) and total knee replacement (TKR) in persons sustaining anterior cruciate ligament (ACL) tear by age 25 years. Methods: We used the Osteoarthritis Policy Model to project the cumulative incidence of symptomatic knee OA requiring TKR in varying situations: no prevalent or incident injury; isolated ACL tear, surgically treated; isolated ACL tear, nonoperatively treated; or a prevalent history or surgically treated ACL and meniscal tear (MT). We estimated MT prevalence and incidence and increased risk of knee OA associated with ACL injury and MT from published literature. We conducted a range of sensitivity analyses to examine the impact of uncertainty in input parameters. Results: Estimated lifetime risk of symptomatic knee OA was 34% for the cohort with ACL injury and MT, compared to 14% for the no-injury cohort. ACL injury without MT was associated with a lifetime risk of knee OA between 16% and 17%, depending on ACL treatment modality. Estimated lifetime risk of TKR ranged from 6% in the no-injury cohort to 22% for the ACL injury and MT cohort. Subjects in the ACL injury and MT cohort developed OA approximately 1.5 years earlier (55.7 versus 57.1) and underwent TKR approximately 2 years earlier (66 versus 68) than the cohort without knee injuries. Conclusion: Sustaining ACL injury early in adulthood leads to greater lifetime risk and earlier onset of knee OA and TKR; concomitant MTs compound this risk. These data provide insight into the impact of sustainable injury prevention interventions in young adults.
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- Whittaker, Jackie L., et al.
(författare)
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Toward designing human intervention studies to prevent osteoarthritis after knee injury : A report from an interdisciplinary OARSI 2023 workshop
- 2024
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Ingår i: Osteoarthritis and Cartilage Open. - 2665-9131. ; 6:2
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The global impact of osteoarthritis is growing. Currently no disease modifying osteoarthritis drugs/therapies exist, increasing the need for preventative strategies. Knee injuries have a high prevalence, distinct onset, and strong independent association with post-traumatic osteoarthritis (PTOA). Numerous groups are embarking upon research that will culminate in clinical trials to assess the effect of interventions to prevent knee PTOA despite challenges and lack of consensus about trial design in this population. Our objectives were to improve awareness of knee PTOA prevention trial design and discuss state-of-the art methods to address the unique opportunities and challenges of these studies. Design: An international interdisciplinary group developed a workshop, hosted at the 2023 Osteoarthritis Research Society International Congress. Here we summarize the workshop content and outputs, with the goal of moving the field of PTOA prevention trial design forward. Results: Workshop highlights included discussions about target population (considering risk, homogeneity, and possibility of modifying osteoarthritis outcome); target treatment (considering delivery, timing, feasibility and effectiveness); comparators (usual care, placebo), and primary symptomatic outcomes considering surrogates and the importance of knee function and symptoms other than pain to this population. Conclusions: Opportunities to test multimodal PTOA prevention interventions across preclinical models and clinical trials exist. As improving symptomatic outcomes aligns with patient and regulator priorities, co-primary symptomatic (single or aggregate/multidimensional outcome considering function and symptoms beyond pain) and structural/physiological outcomes may be appropriate for these trials. To ensure PTOA prevention trials are relevant and acceptable to all stakeholders, future research should address critical knowledge gaps and challenges.
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