Intra-articular Glucocorticoid Injections Research Articles

Calcium pyrophosphate crystal arthritis associated with immune checkpoint inhibitor successfully treated with intra-articular glucocorticoid: A case report.

Immune checkpoint inhibitors (ICIs) sometimes induce immune-related adverse events (irAEs), and arthritis is one of the irAE symptoms. Recently, crystal-induced arthritis, such as calcium pyrophosphate (CPP) crystal deposition disease and gout, has been reported to occur after ICI administration. However, the distinction between ICI-associated crystal arthritis and ICI-induced non-crystal arthritis is difficult because their symptoms are similar. Besides, optimal treatment for ICI-associated crystal arthritis has not been established. Here, we report a patient who developed CPP crystal arthritis twice after pembrolizumab (ICI) administration and was successfully treated with intra-articular glucocorticoid injection. He suffered arthritis and acute interstitial nephritis simultaneously after ICI administration. Musculoskeletal ultrasound of his affected joint suggests that his arthritis was crystal-induced arthritis, and arthrocentesis detected CPP crystal in synovial fluid. Thus, we diagnosed his arthritis as ICI-associated cystal arthritis. Therefore, our case encourages the use of musculoskeletal ultrasound in patients with arthritis after treatment with ICI because it may distinguish between ICI-associated crystal arthritis and ICI-induced non-crystal arthritis. Besides, ICI-associated crystal arthritis could be treatable by intra-articular glucocorticoid injection.

Safety and Efficacy of Radiosynoviorthesis: A Prospective Canadian Multicenter Study.

Radiosynoviorthesis is approved in several European countries and the United States to treat refractory synovitis in many inflammatory joint diseases, such as rheumatoid arthritis, spondyloarthropathies, and other arthritic joint diseases. No radiopharmaceuticals for radiosynoviorthesis are currently approved in Canada. The aim of this Health Canada-approved trial was to demonstrate the safety and efficacy of radiosynoviorthesis. Methods: Between July 2012 and November 2017, we conducted a multicenter, prospective, interventional Canadian trial. Patients (n = 360) with synovitis refractory to standard treatments after failing 2 intraarticular glucocorticoid injections were included. They were followed up at 3, 6, and 12 mo. Outcome measures included adverse events (AEs) and clinical signs of synovitis (pain, swelling, and joint effusion) measured with the Health Assessment Questionnaire Disability Index, the Disease Activity Score, and the Visual Analog Scale. Results: In total, 392 joints were treated, including those reinjected after 6 mo (n = 34). Of these, 83.4% (327/392) were injected with [90Y]Y-citrate for the knees and 9.9% (39/392) with [186Re]Re-sulfide for medium-sized joints. Of the joints treated, 82.7% (324/392) were knees. Fifty-five AEs, most of them of mild grade, occurred and resolved without sequelae and were not life-threatening. The incidence of radiosynoviorthesis-related AEs was 9.4% (34/360). The proportion of patients showing an improvement in synovitis symptoms after radiosynoviorthesis was significant at 3 mo and was maintained up to 12 mo (P < 0.001). Conclusion: This study confirmed the safety of radiosynoviorthesis in the treatment of patients with synovitis refractory to standard treatments. There is evidence of sustained clinical efficacy at 12 mo, suggesting that radiosynoviorthesis is an effective treatment for improving synovitis symptoms.

P072 The management of hand osteoarthritis in the NHS: a national UK clinician-based study

Abstract Background/Aims Hand Osteoarthritis (HOA) is a condition causing significant pain and disability in those affected. Treatments include pharmacological/non-pharmacological approaches, including splinting, pain management with non-steroidal anti-inflammatory drugs (NSAIDs), intra-articular corticosteroid (ICS) injections and surgery. There may be variability in ICS use, since few trials have compared efficacy of ICS over placebo. We conducted a UK-wide study of practising clinicians regarding their management of HOA. Methods An online survey was conducted from September 2022 - May 2023. Practising clinicians who are members of their respective societies were contacted by email. Participants provided information about their job role, region of work, nature of their clinical practice, subtypes of HOA managed and preferred management options. Results A total of 132 complete responses were obtained from the survey. Responding clinicians included Consultant Rheumatologists (43.2%), Consultant Hand Surgeons (34.8%), Rheumatology Specialist Nurses (6.1%), Rheumatology trainees (7.4%), Occupational Therapists (4.6%), Consultant Radiologists (1.5%), Physiotherapists (0.8%), General Practitioners (0.8%) and Physician Associates (0.8%). Responses were obtained from London (25%), South East (12.9%), South West (4.5%), East of England (6.8%), Midlands (12.1%), North West (3.8%), North East (3.8%), Yorkshire and the Humber (28%), Scotland (0.8%) and Wales (2.3%). There were 48.5% of respondents working in tertiary care services, 37.1% in district general hospitals, 13.6% across multiple sites in secondary care and 0.8% in primary care. Ninety-eight per cent of responders were seeing patients with HOA and the most common number of patients seen with HOA was 1-10 per month, reported by 40.3% of respondents. The most common type of HOA observed was first CMC joint or DIP/PIP joint involvement (more than 50%), with a lower proportion for erosive HOA (up to 10%). More than 90% of respondents reported that NSAIDs/hand therapy/intra-articular steroid injections/surgery were the treatments most likely to be offered. Eighty per cent of respondents reported an awareness of splinting, 31% were aware of taping. Regarding ICS, 62.9% performed ICS injections and 37.1% preferred injections under ultrasound (US) guidance. Reasons for preferring injections in clinic included time taken for US guided injections due to pressure on radiology services. Some clinicians preferred US guided confirmation of inflammation before proceeding to injection. Conclusion We obtained a high response rate from clinicians managing HOA. The most common HOA subtype observed was the first CMC, PIP/DIP joints. Recent EULAR (European Alliance of Associations for Rheumatology) recommendations state that ‘intra-articular injections of glucocorticoids should not generally be used in hand OA’, but can be considered in patients with painful PIP/DIP joints. We found high use of ICS injections as an adjunct to other therapies. Injection in clinic was preferred due to pressures on Radiology services. Our data suggest a higher use of ICS in clinical practice in comparison with published guideline recommendations. Disclosure N. Sofat: None. L. Ahmed: None. A. Radulovic: None. S. Cerovac: None. S. Umarji: None.

Effectiveness of Ultrasound-guided versus Landmark-based Glucocorticoid Injection in the Treatment of First Carpometacarpal Joint Osteoarthritis

Background: Osteoarthritis is a debilitating degenerative disease more pronounced in elderly affecting many joints. The first carpometacarpal joint (CMC1) is commonly affected. Pain is the major complaint, which can impact patient’s daily activities. Intra-articular glucocorticoid injection can be considered if conservative measures fail and ultrasound guided injection might be superior to the traditional anatomic landmark-guided technique. Objective: The aim of this study is to evaluate the effectiveness of ultrasound-guided versus landmark-based approach to intra-articular CMC1 injection using the Australian Canadian osteoarthritis hand index (AUSCAN). Methods: Adult patients diagnosed with symptomatic CMC1 osteoarthritis who failed conservative measures were enrolled. In this prospective observational cohort study, utilizing a convenience sample, intra-articular corticosteroid injection was administered either by ultrasound-guided technique or landmark-based approach. Pain, stiffness and function in 10-points scale at baseline, 6 and 12 weeks were collected and analyzed using descriptive analysis. Results: There were 33 patients enrolled. Mean age was 63 years, with females making up the majority of participants (n = 28, 84.8%). Mean duration of CMC1 pain was 10 months (SD=2.5) up to the point of receiving the injection. Ultrasound guided injection was performed in 60.6% (n=20), while 39.4% (n=13) had the landmark approach. Both groups achieved a statistically and clinically significant level of change in AUSCAN score at week 6 (P≤ 0.05) but with a recurrence of symptoms at week 12 (P ≤ 0.05). At both intervals the AUSCAN scores were better than baseline (P ≤ 0.05). There was no difference between the two groups regarding baseline pain VAS score (mean ultrasound group= 6.6 vs landmark group= 7.5; P = 0.18). No significant differences were identified between two groups in terms of changes from baseline to 6, 12 and between 6 to 12 weeks in pain, stiffness and hand function (P &gt; 0.05). Conclusion: No difference was found between the ultrasound-guided and landmark-based approaches for CMC1 injection on pain score, stiffness, or function.

Impact of the COVID-19 Pandemic on the Management of Juvenile Idiopathic Arthritis: Analysis of United States Commercial Insurance Data.

Given limited information on health care and treatment utilization for juvenile idiopathic arthritis (JIA) during the pandemic, we studied JIA-related health care and treatment utilization in a commercially insured retrospective US cohort. We studied rates of outpatient visits, new disease-modifying antirheumatic drug (DMARD) initiations, intra-articular glucocorticoid injections (iaGC), dispensed oral glucocorticoids and opioids, DMARD adherence, and DMARD discontinuation by quarter in March 2018-February 2021 (Q1 started in March). Incident rate ratios (IRR, pandemic vs prepandemic) with 95% confidence intervals (CIs) were estimated using multivariable Poisson or Quasi-Poisson models stratified by diagnosis recency (incident JIA, <12 months ago; prevalent JIA, ≥12 months ago). Among 1294 children diagnosed with JIA, total and in-person outpatient visits for JIA declined during the pandemic (IRR, 0.88-0.90), most markedly in Q1 2020. Telemedicine visits, while higher during the pandemic, declined from 21% (Q1) to 13% (Q4) in 2020 to 2021. During the pandemic, children with prevalent JIA, but not incident JIA, had lower usage of iaGC (IRR, 0.60; 95% CI, 0.34-1.07), oral glucocorticoids (IRR, 0.47; 95% CI, 0.33-0.67), and opioids (IRR, 0.44; 95% CI, 0.26-0.75). Adherence to and discontinuation of DMARDs was similar before and during the pandemic. In the first year of the pandemic, visits for JIA dropped by 10% to 12% in commercially insured children in the United States, declines partly mitigated by use of telemedicine. Pandemic-related declines in intra-articular glucocorticoids, oral glucocorticoids, and opioids were observed for children with prevalent, but not incident, JIA. These changes may have important implications for disease control and quality of life.

SAT295 Metabolic And Endocrine Risks In Association With The Use Of Intraarticular Glucocorticoid Injections: A Retrospective Study

Abstract Disclosure: E. Rabiei-Flori: None. Y. Yin: None. F. Hasan: None. Introduction: The use of intraarticular glucocorticoid injections (IGCI) to alleviate chronic pain from degenerative joint disease (DJD) is very common and the frequency of their use is probably underestimated. In our clinical experience the harmful metabolic effects of the frequent IGCI use are concerning, yet are not well studied. It is well-known that chronic exposure to systemic glucocorticoids is the most common cause of Cushing’s syndrome; i.e., iatrogenic Cushing’s (IC). There are, however, limited data assessing the link between IGCI use and IC. Methods: In this retrospective study we compare the outcomes in two large populations, both of which had received intraarticular injections to alleviate DJD pain. The first population received IGCI, while the second (comparison) population received a non-steroid, hyaluronic acid injection (IAHA). We hypothesize that, compared to the use of IAHA, the use of IGCI is associated with worse metabolic and endocrine outcomes, such as higher frequencies of diabetes, insulin requirement, obesity, hypertension, osteoporosis, and vertebral compression fractures. We included patients aged 18-90 years who received ≥1 IAHA dose versus ≥ 5 IGCI to a major joint (hip, knee, or shoulder) between 1/1/2017-9/30/2021. Results: During the study period 34,600 subjects received at least one of the two treatments (30,273 received IGCI vs 4327 who received IAHA; ratio of IGCI to IAHA population ≈ 7). Among the IGCI population 2421 (8%) received ≥ 5 IGCI injections. Comparisons are provided for this subset vs. IAHA. At baseline, mean age in the IGCI vs IAHA groups were 66.3 (±11.5) and 63.8 (±11.8) years, respectively. The use of IGCI was 2 folds higher and the use of IAHA was 1.5 folds higher in females than males. Most patients were White (88.6% and 90% in the IGCI and IAHA groups, respectively). There was no difference in BMI between the groups at baseline (both 32.7 ± 7). Compared to the IAHA population, those who received ≥ 5 IGCI had significantly higher frequency of incident diabetes (42.1% vs. 35.3%, p 0.0006), requiring insulin therapy for diabetes (14.8% vs 12.6%, p=0.02), hypertension (55.4% vs. 43.6%, p &amp;lt;0.001), osteopenia (7.9% vs 5.7%, p=0.001), osteoporosis (8.8% vs 4.9%, p&amp;lt;0.0001), vertebral compression fracture (2.1% vs. 1.3%, p=0.04), depression (14.3% vs. 9.5%, p&amp;lt;0.001), cataract (3.6% vs. 2 %, p=0.0008), emergency room visit (48.8% vs 43.2%, p &amp;lt; 0.0001), ER visit for hypertension (3.4% vs 2.3%, p=0.02) and hospitalization for any reason (32.6% vs 27%, p&amp;lt;0.0001). Furthermore, the IGCI population had significantly lower lumbar spine BMD on DXA scan (0.98 vs 1.04 g/cm3, p=0.02). In contrast, the prevalence of obesity or severe obesity was not different between the two populations. Conclusion: compared to IAHA, the use of IGCI is associated with increased frequency of endocrine and metabolic risks that are observed in iatrogenic Cushing’s syndrome. Presentation: Saturday, June 17, 2023

Levels of antibodies to adalimumab in children with juvenile idiopathic arthritis at different stages of treatment

Background. Juvenile idiopathic arthritis (JIA) is one of the most common rheumatological diseases of childhood. The central place in the problem of JIA belongs to the question of treatment the timeliness and adequacy of which determine the disease prognosis and, in fact, the entire future of the child. Immunobiological therapy can cause stable clinical and laboratory remission, as well as stop the further progression of structural changes, affecting the pathogenetic link of idiopathic arthritis. But the lack of response to therapy or a decrease in its effectiveness remains a fairly common problem and, in many cases, can be caused by the immunogenicity of immunobiological drugs, especially in case of treatment with tumor necrosis factor inhibitors. Aim of the work: to study the level of antibodies to adalimumab in children with juvenile idiopathic arthritis at different stages of treatment for analysis of immunogenicity. Materials and methods. The concentration of antibodies to adalimumab in 80 serum samples from patients with JIA was studied and evaluated, treatment effectiveness and adverse events were analyzed in 56 patients with JIA at different stages of therapy. Two groups were identified. The first one included 24 patients who had at least a 6-month break in adalimumab administration for non-medical reasons during which treatment was continued with methotrexate with periodic intra-articular injection of glucocorticoids. The level of antibodies to adalimumab was evaluated before the break and 1 month after the reinitiation of adalimumab administration. The second group consisted of 32 children who continued adalimumab without a break during treatment. Disease activity was measured using JADAS-27. Antibodies to adalimumab were detected by enzyme-linked immunosorbent assay. Results. During the examination, an elevated level of antibodies to adalimumab was detected in 10 of 24 serum samples (42 %) before non-medical withdrawal in group I. Among the results of group II, elevated levels of antibodies to adalimumab were found in 12 samples, which was 38 %. The correlation analysis revealed direct statistically significant relationships of moderate strength between the level of antibodies to adalimumab and the indicator of inflammatory activity on JADAS-27 (Spearman’s r = 0.39, p &lt; 0.05), as well as between the level of antibodies and disease duration (Spearman’s r = 0.32, p &lt; 0.05). Conclusions. Monitoring serum antibodies to adalimumab is informative for the correct interpretation of treatment effectiveness and the course of the disease with immunobiological treatment, as it may improve understanding of the clinical consequences of continued therapy, help prevent adalimumab immunogenicity, develop follow-up strategies and, as a result, can affect a long-term outcome of treatment for JIA.

Mask parathyroid adenoma in morbid obese woman with secondary adrenal insufficiency

Abstract Introduction Primary hyperparathyroidism (PHPT) and metabolic syndrome (MS) are independently increase cardiovascular morbidities; however, this association is still controversial. The pathogenic mechanisms of MS among PHPT are not completely clear and the association with calcium metabolism is being studied, since calcium is pivotal for many metabolic processes. The association between these entities is complex and may be a source of additional morbidity and mortality. Objective is to highlight the mask features of parathyroid adenoma in morbid obese woman with secondary adrenal insufficiency. Clinical case A 33-year-old female presented with discomforting polyarthralgia and weight gain for the last 2 years that was labelled as nonspecific arthritis and treated by multiple intra-articular injections of glucocorticoids. After a careful history and examination with baseline analysis, she was discovered to have MS (dysglycemia, high insulin resistance and hypertension). A feature glucocorticoid induced adrenal insufficiency was documented and work up for any evidence of osteoporosis was initiated. A high parathyroid hormone with hypercalcemia was documented and an established osteoporosis was evident. Furthermore, a large left side parathyroid adenoma was observed by a neck sonography and confirmed by a four-dimension computed tomography of the neck. Surgical exploration with excision of the parathyroid adenoma was performed, following which the patient recovered uneventfully. The patient was initially managed as a case of MS with secondary adrenal insufficiency due to glucocorticoid misuse. Although not suspected initially, an extensive work up for osteoporosis screening and accidental hypercalcemia increase the chance of high index of suspicion for hyperparathyroidism. Further investigations then revealed the presence of a solitary parathyroid adenoma with coexistent hyperparathyroidism which was then managed surgically. Conclusion Despite the majority of PHPT is asymptomatic and over masked by MS, Active surveillance for any evidence of hypercalcemia and bone metabolism have to be judged carefully to reduce further morbidity and mortality.

Efficacy and safety of GLucocorticoid injections into InfrapaTellar faT pad in patients with knee ostEoarthRitiS: protocol for the GLITTERS randomized controlled trial

BackgroundKnee osteoarthritis (OA) is a prevalent disabling disorder that involves changes in articular cartilage damage, subchondral bone remodeling, synovitis, and abnormal infrapatellar fat pad (IPFP). Due to the complicated etiology and numerous phenotypes of knee OA, limited improvement is achieved for treatments among knee OA patients with different phenotypes. Inflammatory OA phenotype is a typical knee OA phenotype, and individualized treatment targeting inflammation is a promising way to obtain an optimal therapeutic effect for people with inflammatory knee OA phenotype. Glucocorticoid is a traditional anti-inflammatory drug for knee OA, and intra-articular glucocorticoid injections are recommended clinically. However, emerging evidence has shown that repeated intra-articular glucocorticoid injections in the long term would induce cartilage loss. IPFP and its adjacent synovium are considered as the main source of inflammation in knee OA. This GLITTERS trial aims to investigate if a glucocorticoid injection into the IPFP is effective and safe over 12 weeks among knee OA patients with an inflammatory phenotype.MethodsGLITTERS is a multicenter, double-blinded, randomized, and placebo-controlled clinical trial among knee OA patients with both Hoffa-synovitis and effusion-synovitis. Sixty participants will be allocated randomly and equally to either the glucocorticoid group or the control group. Each group will receive an injection of glucocorticoid or saline into the IPFP with an intra-articular hyaluronic acid injection as a background treatment at baseline and be followed at 4, 8, and 12 weeks. The primary outcomes will be changes in knee pain on a visual analog scale and effusion-synovitis volume measured on magnetic resonance imaging (MRI). The secondary outcomes will be changes in the total score of Western Ontario and McMaster Universities Osteoarthritis Index score, MRI-detected Hoffa-synovitis score, quality of life, pain medication use, IPFP volume, and the incidence of adverse reactions. Data analyses based on the intention-to-treat principle will include mixed-effects regressions, Wilcoxon rank-sum tests, and chi-square tests (or Fisher’s exact test).DiscussionGLITTERS may provide high-quality evidence for the efficacy and safety of ultrasound-guided glucocorticoid injections into IPFP among people with inflammatory knee OA in a short term. The results of this trial are expected to provide a reliable reference for a longer-term risk–benefit profile of this treatment in the future.Trial registrationClinicalTrials.gov NCT05291650. Registered on 23 March 2022.

Test-Retest Reliability and Sensitivity to Change of Ultrasound-Based Methods of Measuring Synovial Inflammation in Knee Osteoarthritis.

To assess test-retest reliability of musculoskeletal ultrasound (US) measures of inflammation in patients with knee osteoarthritis (OA) and to assess the sensitivity to change of US measures of inflammation in patients with knee OA. To mimic a common clinical scenario, 36 patients (n=70 knees) with symptomatic knee OA who were in stable condition underwent 2 assessments within 14 days by different operators and different US machines, graded by a single rater. Test-retest reliability was measured using Cohen's kappa coefficient, intraclass correlation coefficient (ICC), and absolute agreement parameters. A total of 51 patients (n=72 knees) were tested immediately before and 21-28 days after intraarticular glucocorticoid injection to investigate sensitivity to change and longitudinal construct validity. Paired t-tests and standardized response mean (SRM) were used to assess sensitivity to change. Multivariate linear regression was used to investigate longitudinal construct validity of US with Knee Injury and Osteoarthritis Outcome Score (KOOS) pain scores, while adjusting for covariates. US measures of inflammation demonstrated moderate (κ=0.41, 0.60) to substantial (κ=0.61, 0.80) agreement. Quantitative measures of synovitis and effusion demonstrated good test-retest reliability (ICC2,1 0.71, 0.92). US measures of synovitis and effusion demonstrated low-to-moderate sensitivity to change (SRM -0.29, -0.50). The associations between changes in US measures and KOOS pain scores over time were low, and 95% confidence intervals included zero. In a clinical setting, US measures of inflammatory features of knee OA have substantial reliability and low-to-moderate sensitivity to change, whereas measures of structural OA features are less reliable. Longitudinal construct validity of US measures of synovitis and effusion to KOOS pain scores is not strongly supported.

Increased Chondroprotective Effect of Combining Hyaluronic Acid with a Glucocorticoid Compared to Separate Administration on Cytokine-Treated Osteoarthritic Chondrocytes in a 2D Culture

Intra-articular injections of glucocorticoids (GC) or hyaluronic acid (HA) are commonly used interventions for patients suffering from knee osteoarthritis (OA). Both substances are combined to achieve a chondroprotective and anti-inflammatory effect. Clinical studies have shown benefits, but data on the cellular level are still lacking. This study aimed to investigate the effect of the GC triamcinolone hexacetonide, HA, and a mix of both substances on cytokine-treated chondrocytes in vitro. Chondrocytes isolated from human articular cartilage were seeded on 6- and 24-well plates. Mimicking OA’s inflammatory state, cells were treated with IL-1β and IL-17 for six days, whereby, after three days, test substances (10%) were added to the culture medium. Chondrocytes were analyzed on days three and six concerning their actin polymerization, expression of anabolic and catabolic genes, metabolic activity, cytokine release, and reactive oxygen species (ROS). Adding HA or GC/HA to the inflammatory culture medium increased the metabolic activity of chondrocytes, while groups containing GC reduced catabolic gene expression and the release of TNF-α. In addition, enhanced F-actin content was shown supplementing HA or GC/HA to the culture medium. Supplementing GC with HA leads to an anti-inflammatory and chondroprotective effect by diminishing the side effects of GC supplementation alone.

Optimizing the anti-inflammatory strategies in (osteo)arthritis: local or systemic?

Arthritis is affecting millions of people globally, involvement and distribution depending on the type of arthritis. The most common arthritic conditions are osteoarthritis (OA) and rheumatoid arthritis (RA). Despite the pathogeneses being fundamentally different, both joint diseases share the same need for local treatment of synovitis. No current treatment can stop the progression of OA. Local articulate treatment including glucocorticoid (GC) injections, radiosynoviorthesis (RSO) and surgical synovectomy are the only options to relieve pain and temporally improve movability before surgical intervention. For RA, despite effective systemic treatments, similarly need for local articulate treatment is still present, especially early in the disease, but also in case of recurrent episodes of disease flare. Current evidence supports local GC injection as first line treatment for persistent synovitis in a single or a few joints. RSO provides an evident and effective alternative for GC refractory synovitis, especially in early RA. Surgical synovectomy is an invasive alternative, but with less documented efficacy. Whether one unsuccessful intraarticular GC injection is enough to change of mode of action for local treatment is still unclear and needs to be further investigated. In conclusion persistent single joint synovitis in OA and RA is well treated with local treatment. Intra-articular GC injection is considered as first line of treatment, but RSO provides an additional treatment alternative with less side effects and better evidence of efficacy than surgical synovectomy.

Do Glucocorticoid Injections Increase the Risk of Knee Osteoarthritis Progression Over 5 Years?

Recent findings have demonstrated that intraarticular (IA) glucocorticoid injections can be deleterious for knees with osteoarthritis (OA). This study was undertaken to assess, in a real-life setting, the risk of knee OA progression in patients who received IA glucocorticoid injections over a 5-year follow-up period. We used marginal structural modeling with inverse probability of treatment weighting to determine the causal association between IA glucocorticoid injections and the 5-year risk of disease progression in patients with symptomatic knee OA from the Knee and Hip Osteoarthritis Long-term Assessment cohort. OA progression was defined as an incident total knee replacement (TKR) and/or radiographic worsening (Kellgren/Lawrence [K/L] grade or joint space narrowing [JSN]). We also examined these outcomes in knees that received IA hyaluronan (IAHA) injections. Among the 564 patients with knee OA included in the study sample, 51 (9.0%) and 99 (17.5%) received IA glucocorticoid or IAHA injections, respectively, and 414 (63.1%) did not receive any injection during follow-up. Compared to untreated knees, those treated with IA glucocorticoid injections had a similar risk of incident TKR (hazard ratio [HR] 0.92 [95% confidence interval (95% CI) 0.20, 4.14]; P = 0.91) or K/L grade worsening (HR 1.33 [95% CI 0.64, 2.79]; P = 0.44). IAHA injections had no effect on the risk of TKR (HR 0.81 [95% CI 0.14, 4.63]; P = 0.81) or K/L grade worsening (HR 1.36 [95% CI 0.85, 2.17]; P = 0.20). Similar results were obtained for JSN, and when TKR and radiographic outcomes were combined. In this study, IA glucocorticoid injections for symptomatic knee OA did not significantly increase the 5-year risk of incident TKR or radiographic worsening. These findings should be interpreted cautiously and replicated in other cohorts.

Effect of Intramuscular vs Intra-articular Glucocorticoid Injection on Pain Among Adults With Knee Osteoarthritis

Intra-articular (IA) glucocorticoid injection is widely used in patients with knee osteoarthritis (OA), but the safety of this technique is in question among physicians. Intramuscular (IM) glucocorticoid injection could be an alternative approach. To investigate whether an IM glucocorticoid injection is noninferior to an IA glucocorticoid injection in reducing knee pain for patients with knee OA in primary care. The KIS trial, a multicenter, open-label, randomized clinical noninferiority trial including patients with symptomatic knee OA, was conducted in 80 primary care general practices in the southwest of the Netherlands. The study was conducted from March 1, 2018, to July 28, 2020. Patients were randomly allocated to receive an injection of triamcinolone acetonide, 40 mg, either IM in the ipsilateral ventrogluteal region or IA in the knee joint. All patients were followed up for 24 weeks. The pain score at 4 weeks measured with Knee Injury and Osteoarthritis Outcome Score (range, 0-100; 0 indicates extreme pain), with a noninferiority margin of -7 (IM minus IA). A per-protocol analysis was prespecified as the primary analysis. A total of 145 patients (94 women [65%]; mean [SD] age, 67 [10] years) were included; of these, 138 patients (IM, 72; IA, 66) were included in the per-protocol analysis. Clinically relevant improvements in knee pain were reached up to 12 weeks after the injection in both groups. At 4 weeks, the estimated mean difference in the Knee Injury and Osteoarthritis Outcome Score between the 2 groups was -3.4 (95% CI, -10.1 to 3.3). Noninferiority could not be declared because the lower limit exceeded the noninferiority margin. Intramuscular injection was noninferior to IA injection at 8 (mean difference, 0.7; 95% CI, -6.5 to 7.8) and 24 (mean difference, 1.6; 95% CI, -5.7 to 9.0) weeks. No significant difference was found among all the secondary outcomes. These results were similar for the sensitivity analysis in an intention-to-treat population. The most frequently reported adverse events were hot flush (IM, 7 [10%] vs IA, 14 [21%]) and headache (IM, 10 [14%] vs IA, 12 [18%]), and all events were classified as nonserious. Based on the findings of this trial, among patients with knee OA in primary care, IM glucocorticoid injection could present an inferior effect in reducing pain at 4 weeks compared with IA injection. Noninferiority of an IM injection was observed at 8 and 24 weeks after injection. This trial provides data for shared decision-making, taking into account the advantages and disadvantages of both types of injections. Dutch Trial Registry: NTR6968.

Arthroscopic surgery for degenerative knee disease (osteoarthritis including degenerative meniscal tears).

Arthroscopic surgery for degenerative knee disease (osteoarthritis including degenerative meniscal tears).

Evaluation of the effectiveness of intra-articular injections of glucocorticoids in knee synovitis in patients with rheumatic diseases in real clinical practice

Intra-articular injections of glucocorticoids are widely used in the complex therapy of rheumatic diseases (RD). However, there is insufficient data on their effectiveness and safety in real clinical practice.The aim of the study – to evaluate the effectiveness of intra-articular injections of glucocorticoids in rheumatic diseases in real clinical practice.Material and methods. The study group consisted of 290 patients with RD, mainly osteoarthritis (OA) and rheumatoid arthritis (RA) (69.0% – women; age – 55.6±12.6 years), who underwent intra-articular injections of glucocorticoids in the knee joint. Indications for intra-articular injections of glucocorticoids were determined by the attending physicians. The control group consisted of 112 patients with OA (71.4% – women; age 59.3±14.6 years) who underwent a course of intra-articular injections of hyaluronic acid. The result of treatment was evaluated in 2 weeks, 1 and 3 months according to a telephone survey.Result. After 2 weeks, 1 month and 3 months after the intra-articular injections of glucocorticoids, the severity of pain during movement decreased (numerical rating scale (NRS) 0–10; Me [25%; 75%]) from 6.0 [4.0; 8.0] to 1,0 [0; 2,0], 2,0 [1,0; 4,0] and 2.5 [1.0; 4.0] respectively (p&lt;0.001). After 3 months, the number of patients with no pain or mild pain (&lt;4 NRS) was 63.8%, with complete/almost complete absence of pain (≤1 NRS) – 30.3%. The effect of intraarticular injections of glucocorticoids was higher in RA than in OA: pain dynamics after 3 months –4.0 [–2.0; –6.0] and –2.0 [–1.0; –5.0] respectively (p=0.003). In OA, the effect of intra-articular injections of glucocorticoids and of hyaluronic acid did not differ: the dynamics of pain after 3 months was –2.0 [–1.0; –5.0] and –3.0 [–1.0; –5.0] respectively (p=0.869). No serious adverse reactions were noted at intra-articular injections of glucocorticoids.Conclusions. Intra-articular injections of glucocorticoids are an effective and fairly safe method of short-term treatment of synovitis in rheumatic diseases.

Osteoarthritis: what's new?

Osteoarthritis (OA) is a very common disease. As a consequence of the ageing society, osteoarthritis prevalence will further increase. Age itself, trauma, unequal load distribution and overweight are risk factors. Cellular senescence and overweight have been in the focus of scientific interest for the last few years. Both risk factors are able to facilitate joint inflammation, independent of a mechanical approach. Senescent chondrocytes as well as adipocytes can produce increased amounts of inflammatory cytokines. Cornerstones of the therapy are patient education including information on the character/course of the disease and intentional weight loss. Although NSAIDs can be recommended as analgesics, their contraindications limit the widespread use. Alternatively, acetaminophen or low-potency opioids such as tramadol might be considered. Topical NSAIDs and intraarticular glucocorticoid injections can be helpful in pain reduction particularly in knee osteoarthritis. There is still no general recommendation for nutritional supplements including chondroitin or glycosaminoglycan, but they might be considered as an accompanying therapy. With the current non-approval of the nerve growth factor (NGF)-antibody tanezumab, a new therapeutical option for OA suffered a setback. Unfortunately, the results of the phase 2 study on the Wnt inhibitor lorecivivint are barely encouraging. However, the results of the according phase 3 study are eagerly awaited.

Cost-effectiveness of Physical Therapy vs Intra-articular Glucocorticoid Injection for Knee Osteoarthritis

Physical therapy and glucocorticoid injections are initial treatment options for knee osteoarthritis, but available data indicate that most patients receive one or the other, suggesting they may be competing interventions. The initial cost difference for treatment can be substantial, with physical therapy often being more expensive at the outset, and cost-effectiveness analysis can aid patients and clinicians in making decisions. To investigate the incremental cost-effectiveness between physical therapy and intra-articular glucocorticoid injection as initial treatment strategies for knee osteoarthritis. This economic evaluation is a secondary analysis of a randomized clinical trial performed from October 1, 2012, to May 4, 2017. Health economists were blinded to study outcomes and treatment allocation. A randomized sample of patients seen in primary care and physical therapy clinics with a radiographically confirmed diagnosis of knee osteoarthritis were evaluated from the clinical trial with 96.2% follow-up at 1 year. Physical therapy or glucocorticoid injection. The main outcome was incremental cost-effectiveness between 2 alternative treatments. Acceptability curves of bootstrapped incremental cost-effectiveness ratios (ICERs) were used to identify the proportion of ICERs under the specific willingness-to-pay level ($50 000-$100 000). Health care system costs (total and knee related) and health-related quality-of-life based on quality-adjusted life-years (QALYs) were obtained. A total of 156 participants (mean [SD] age, 56.1 [8.7] years; 81 [51.9%] male) were randomized 1:1 and followed up for 1 year. Mean (SD) 1-year knee-related medical costs were $2113 ($4224) in the glucocorticoid injection group and $2131 ($1015) in the physical therapy group. The mean difference in QALY significantly favored physical therapy at 1 year (0.076; 95% CI, 0.02-0.126; P = .003). Physical therapy was the more cost-effective intervention, with an ICER of $8103 for knee-related medical costs, with a 99.2% probability that results fall below the willingness-to-pay threshold of $100 000. A course of physical therapy was cost-effective compared with a course of glucocorticoid injections for patients with knee osteoarthritis. These results suggest that, although the initial cost of delivering physical therapy may be higher than an initial course of glucocorticoid injections, 1-year total knee-related costs are equivalent, and greater improvement in QALYs may justify the initial higher costs. ClinicalTrials.gov Identifier: NCT01427153.

Analysis of Some Immunological Aspects of Joint Infections Developed as a Result of Intra-Articular Glucocorticoid Injection

Summary. The work is devoted to the studies of immune status of patients with infectious complications after local glucocorticoid injections.&#x0D; Objective: to assess the state of the immune system of patients with infectious complications after local glucocorticoid injections, to monitor the dynamics of immunological parameters before and after sanitizing surgical treatment, and to reveal factors that are important for predicting the course of the disease and treatment results.&#x0D; Materials and Methods. The immune status of 26 patients with purulent inflammatory processes after local glucocorticoid injections in rheumatoid arthritis, deforming osteoarthritis, and chronic synovitis was studied. Immunological, hematological, and statistical research methods were used.&#x0D; Results. Changes of immunity factors as well as hematological parameters were revealed: a decrease in the content of T-lymphocytes (CD3+), T-helpers (CD4+), T-suppressors / cytotoxic lymphocytes (CD8+), immunoglobulins of classes A, M, and G; an increase in the levels of circulating immune complexes (СIC), the number of thrombocytes, erythrocyte sedimentation rate (ESR), and the reaction of the neutrophil leukocytes. It has been shown that the improvement of the immune status and the decrease in the level of inflammatory reactions after the sanitizing surgical intervention occurs slowly, which requires the inclusion of immunocorrective therapy in the treatment of such patients.&#x0D; Conclusions. Primary examination of patients before surgery for the purpose of sanitizing the infection showed that the local inflammatory process in the bones and joints occurs against the background of altered immunological and hematological parameters. Dynamic follow-up showed that we are dealing not only with a local process, but also with a systemic inflammatory response. A variant of the laboratory criterion for the course of infectious complications and the effectiveness of the treatment can be the determination in the dynamics of the content of T-lymphocytes and their subpopulations, the levels of the CIC, platelets and ESR.

Intra-articular glucocorticoid injection site: best practice guidelines

The article presents modern recommendations for the use of systemic administration of glucocorticoids. It is indicated that there is a clear tendency to minimize the doses and timing of the appointment of systemic glucocorticoids in rheumatoid arthritis, and in seronegative spondyloarthropathies (ankylosing spondylitis, psoriatic arthritis), in accordance with both foreign and domestic recommendations, systemic therapy with glucocorticoids is not carried out. It is emphasized that at the present stage, the role of local administration of glucocorticoids will increase as an effective way to reduce the activity of arthritis in any nosologically form. The mechanisms of action of locally administered glucocorticoids leading to anti-inflammatory and analgesic effects are described. The comparative characteristics of locally administered glucocorticoids with different duration of action according to their effectiveness and safety are presented. Predictors of the effectiveness of local therapy with glucocorticoids are described. The data on the evaluation of the duration of the anti-inflammatory and analgesic effects of various local glucocorticoids, including in comparison with the intra-articular administration of hyaluronic acid preparations, which showed the advantages of betamethasone over triamcinolone acetate, are presented. The differences in the crystal structure of betamethasone and triamcinolone acetate are described. It is indicated that the 2.5-fold smaller size of betamethasone crystals compared to triamcinolone acetate crystals and the absence of betamethasone crystals makes it possible to use betamethasone in the treatment of inflammatory processes in periarticular tissues, as well as in crystalline arthritis (gout, pseudogout). The data on the safety of the use of intra-articular injection of glucocorticoids are presented. It is indicated that the registration in the Russian Federation of a new form of betamethasone in pre-filled syringes makes it even more possible to avoid infectious complications of this type of therapy. Rare cases of complications of local therapy with glucocorticoids are described.