Corticosteroid Injections for Symptomatic Treatment of Osteoarthritis of the Knee: A Pilot Blinded Randomized Trial.

OBJECTIVE: To quantify the effect of corticosteroids compared to lidocaine-only injections over 12 weeks among patients with knee osteoarthritis (KOA). METHODS: Participants with KOA were randomized to receive a knee injection of methylprednisolone acetate 1 mL (40 mg) plus 2 mL lidocaine (1%) or 1 mL saline and 2 mL lidocaine. Participants and providers were blinded to treatment allocation using an opacified syringe. The outcome was the average change from baseline of the total Knee Injury and Osteoarthritis Outcome Score (KOOS) (range 0-100) assessed at 2-week intervals over 12 weeks. Participants received KOOS questionnaires on their smartphones through a web-based platform. We used linear mixed-effects regressions with robust variance estimators to evaluate the association between the intervention and change in KOOS total and subscales (ClinicalTrials.gov identifier NCT03835910; registered 2019-02-11). RESULTS: Of the 33 randomized participants, 31 were included in the final analysis. The predicted mean (SE) change in total KOOS over the 12-week follow-up was 9.4 (3.2) in the corticosteroids arm versus -1.3 (1.4) in the control arm (P = 0.003). Of participants, 47% achieved change as large as the minimal clinically important difference (16 units) in the intervention arm compared to 6% of participants in the lidocaine arm. Further, there were greater improvements in the intervention arm for KOOS subscales and for Patient Reported Outcomes Measurement Information System (PROMIS) assessments of pain intensity, behavior, and interference. CONCLUSION: Corticosteroid injections demonstrated clinically meaningful improvements in KOA symptoms over 12 weeks of follow-up. These data support larger studies to better quantify short-term benefits.

Hydroxychloroquine and Risk of Long QT Syndrome in Rheumatoid Arthritis: A Veterans Cohort Study With Nineteen-Year Follow-up.

OBJECTIVE: Recent evidence suggests that hydroxychloroquine use is not associated with higher 1-year risk of long QT syndrome (LQTS) in patients with rheumatoid arthritis (RA). Less is known about its long-term risk, the examination of which was the objective of this study. METHODS: We conducted a propensity score-matched active-comparator safety study of hydroxychloroquine in 8,852 veterans (mean age 64 ± 12 years, 14% women, 28% Black) with newly diagnosed RA. A total of 4,426 patients started on hydroxychloroquine and 4,426 started on another nonbiologic disease-modifying antirheumatic drug (DMARD) and were balanced on 87 baseline characteristics. The primary outcome was LQTS during 19-year follow-up through December 31, 2019. RESULTS: Incident LQTS occurred in 4 (0.09%) and 5 (0.11%) patients in the hydroxychloroquine and other DMARD groups, respectively, during the first 2 years. Respective 5-year incidences were 17 (0.38%) and 6 (0.14%), representing 11 additional LQTS events in the hydroxychloroquine group (number needed to harm 403; [95% confidence interval (95% CI)], 217-1,740) and a 181% greater relative risk (95% CI 11%-613%; P = 0.030). Although overall 10-year risk remained significant (hazard ratio 2.17; 95% CI 1.13-4.18), only 5 extra LQTS occurred in hydroxychloroquine group over the next 5 years (years 6-10) and 1 over the next 9 years (years 11-19). There was no association with arrhythmia-related hospitalization or all-cause mortality. CONCLUSIONS: Hydroxychloroquine use had no association with LQTS during the first 2 years after initiation of therapy. There was a higher risk thereafter that became significant after 5 years of therapy. However, the 5-year absolute risk was very low, and the absolute risk difference was even lower. Both risks attenuated during longer follow-up. These findings provide evidence for long-term safety of hydroxychloroquine in patients with RA.

Protocol for a multi-center randomized controlled trial to evaluate the benefits of exercise incentives and corticosteroid injections in osteoarthritis of the knee (MOVE-OK).

BACKGROUND: Knee osteoarthritis (KOA) is a high-priority problem among the aging population. While exercise has been shown to be beneficial in management of the disease, scalable and low-cost interventions to improve exercise in this population are lacking. Recent controversy over the value of corticosteroid injections for palliation has also arisen. Therefore, we designed a randomized, double-blind, placebo-controlled clinical trial with a 2-period crossover design to study (1) behavioral incentives to promote exercise and (2) corticosteroid injections to reduce pain and improve function in patients with KOA when compared to lidocaine only. METHODS: The study design is a pragmatic factorial and crossover randomized clinical trial. Patients with KOA who are deemed eligible by their provider to receive knee injections and are able to walk without assistive devices will be recruited from clinical practices at four sites within the Veterans Affairs (VA) Health System in the USA. In total, 220 participants will be randomized to receive social incentives with gamification (i.e., incorporation of game elements) to promote exercise and compared to controls that receive a Fitbit but no incentive. Each patient will also be assigned to receive a blinded corticosteroid injection and a lidocaine-only injection in random order. The primary outcomes are the change in average daily step counts from baseline and the change in Knee Osteoarthritis Outcome Score (KOOS) from baseline. The study team will continuously collect step count, heart rate, and sleep data using activity monitors and patient-reported outcomes using the Way to Health (WTH) platform at two four-week intervals over eight months of follow-up. Mixed effects regression incorporating all available data points will be used for analysis. DISCUSSION: The "Marching on for Veterans with Osteoarthritis of the Knee" (MOVE-OK) trial will take a pragmatic approach to evaluate (1) whether incentives based on behaviorally enhanced gamification can improve physical activity in this patient population and (2) whether corticosteroids injections reduce pain and disability in patients with KOA. Results of this trial will help to direct clinical practice and inform management guidelines. TRIAL REGISTRATION: ClinicalTrials.gov NCT05035810 . Registered on 5 September 2021.

How to use biologic agents in patients with rheumatoid arthritis who have comorbid disease.

Although biologic disease modifying anti-rheumatic drugs (bDMARDs) have improved the quality of life of patients with rheumatoid arthritis, side effects remain a problem, especially for patients with pre-existing comorbidities. Randomized controlled trials of such drugs in rheumatoid arthritis typically exclude patients with comorbidities and are of short duration, so they do not provide data on adverse events in these people. Other data sources such as national bDMARD registries are limited by the preselection of patients for both conventional synthetic chemical compound disease modifying anti-rheumatic drugs (csDMARDs) and bDMARDs, and although these databases document comorbidity, they rarely report its severity. This too limits definitive statements on the progression or resolution of pre-existing disease. Although bDMARDs may not be contraindicated in patients with rheumatoid arthritis and certain comorbid diseases, additional assessments or precautions are recommended. This review summarizes current data on the use of bDMARDs in people with rheumatoid arthritis and common comorbid diseases. It provides an evidence base for doctors and their patients when discussing and selecting the appropriate bDMARDs.