Tender Joint Research Articles

P084 Gout symptom improvements and patient outcomes with SEL-212 in gout refractory to conventional therapy: DISSOLVE I & II phase 3, double-blind, placebo-controlled clinical trials

Abstract Background/Aims Serum uric acid (sUA) ≥6.8 mg/dL often leads to severe clinical manifestations in gout refractory to conventional therapy. Uricase-based therapies can be effective, although immunogenicity can reduce efficacy and increase infusion-reaction risk. SEL-212 is a novel, once-monthly treatment of sequential infusions of tolerogenic nanoparticles containing sirolimus (SEL-110) followed by a pegylated uricase (pegadricase, SEL-037). DISSOLVE I and II (DI and DII) evaluated the safety/efficacy of SEL-212 in adults with refractory gout. Here we report secondary and key safety endpoints. Methods DI (US) and DII (Global) were placebo-controlled, double-blind, randomised clinical trials that evaluated a combination of SEL-110 at either 0.15 mg/kg [high-dose] or 0.1 mg/kg [low-dose] with SEL-037 (0.2 mg/kg) in refractory gout. Six-month outcomes included sUA reduction, number of tender/swollen joints, tophus burden, health-related quality-of-life, and safety. Results 112 participants (96% male, 66% aged ≥50 years, DI) and 153 participants (97% male, 72% ≥50 years, DII) were dosed (Table 1). Mean age was 55 years, 57% (DI) and 67% (DII) had tophi at baseline, and time since gout diagnosis was 12.9 (DI) and 11.0 years (DII). Both SEL-212 doses significantly reduced mean sUA levels versus placebo over 6-months (5.2-5.6 mg/dL in DI and 3.3-4.5 mg/dL in DII, p < 0.001 for all), with marked reductions during the first-treatment period. In DII, tender joints declined significantly between baseline and six-months in the high- and low-dose groups (8.1 joints, p = 0.003; 9.2 joints, p < 0.001, respectively) versus placebo (4.4 joints). Swollen joints were also significantly reduced with high-dose SEL-212 (5.7 joints, p = 0.013) versus placebo (3.4 joints). There were significant improvements in SF-36 physical component score with both SEL-212 doses versus placebo (p ≤ 0.01), while HAQ-DI was significantly improved with low-dose versus placebo (p = 0.018) in DII. In DI non-statistically significant trends favouring SEL-212 across all secondary endpoints were observed. This may reflect the smaller sample size and milder baseline symptom burden of patients in DI versus DII. Infusion reactions occurred in 3.4% of the combined high-dose groups. Conclusion SEL-212 was well tolerated and provided significant reductions in mean sUA over time, improvement in SF-36 physical and HAQ-DI measures and reduced the number of tender/swollen joints. Disclosure H.S.B. Baraf: Corporate appointments; Sobi, Selecta BioScience, Grünenthal, Fresenius Kabi and Olatec. Member of speakers’ bureau; Horizon Pharmaceuticals. Grants/research support; Horizon Pharmaceuticals, Swedish Orphan Biovitrum. P. Khanna: Consultancies; Horizon, Sobi. Other; Investigator: Selecta Bioscience, Dyve Biosciences. A. Patel: Member of speakers’ bureau; Lexicon Pharmaceuticals. J. Sobierska: Other; Employee of Sobi. J. Christie: Shareholder/stock ownership; GSK Pharma. Other; Employee of Sobi. W. DeHaan: Shareholder/stock ownership; Selecta Biosciences. Other; Employee of Selecta Biosciences. R. Azeem: Shareholder/stock ownership; Selecta Biosciences. Other; Employee of Selecta Biosciences;. P.G. Traber: Shareholder/stock ownership; Selecta Biosciences. Other; Employee of Selecta Biosciences. A. Kivitz: Consultancies; AXDEV Group, Amgen, Pfizer, Janssen, Boehringer Ingelheim, AbbVie, Flexion, Gilead, Grünenthal, Orion, Regeneron, Sun Pharma Advance Research, and ECOR1. Shareholder/stock ownership; Pfizer, GSK, Gilead, Novartis, and Amgen. Member of speakers’ bureau; Merck & Co, Eli Lilly, Novartis, Pfizer, Flexion, AbbVie, Amgen, Genentech, Regeneron, UCB, Horizon, and GSK.

OA40 Clinical and psychological factors associated with adherence based on a patient self-reported questionnaire: results from the biologics in rheumatoid arthritis genetics and genomics study syndicate (BRAGGS) cohort

Abstract Background/Aims To explore the relationship of clinical and psychological factors with adherence based on a patient self-reported questionnaire from a prospective longitudinal study of patients receiving TNFi biologic treatment for rheumatoid arthritis, recruited since 2008. Methods Analysis of data collected from a prospective longitudinal UK study (Biologics in Rheumatoid Arthritis Genetics and Genomics Study Syndicate [BRAGGSS]) of patients with moderate to severe RA commencing TNFi biologic treatment. Clinical data including Disease Activity Score-28 (DAS28), serological status (Rheumatoid Factor positivity) and body mass index (BMI) were collected. Patients also completed self-reported questionnaires, the health assessment questionnaire (HAQ), hospital anxiety and depression scale (HAD), beliefs about medicine questionnaire (BMQ), brief illness perception score (B-IPQ) and a self-reported adherence questionnaire. Adherence was defined as any deviation from prescribed medication regime such as altering the dose, forgetting a dose, stopping treatment, missing a dose, and taking less than instructed. Associations between demographic and psychological variables and adherence were evaluated using regression models and a multivariable logistic regression model was used to further evaluate associations, controlling for BMI. Results 1,513 patients (75.7% female, age 58.1 [IQR 16.0], disease duration 9.6 ± 9.6 years and pre-treatment DAS28 scores 5.7 ± 0.8) were included. 70% of patients self-reported adherence to their medication. When comparing the different TNFi treatments, etanercept had the lowest levels of adherence at the 3 and 6 month time-points. Adherence was higher in those with older age (β = 0.03, p< 0.01), higher baseline CRP levels (β = 0.01, p= 0.03) and higher necessity beliefs (β = 0.04, p= 0.03). Adherence was lower in those with higher tender joint counts at baseline (β=-0.03, p= 0.04) and 3 months (β = 0.03, p= 0.02) (Table I). These associations persisted after controlling for the effects of BMI using a multivariable logistic model. Conclusion Self-reported adherence was 70% in this BRAGGS population. Factors associated with non-adherence included higher tender joint counts and lower necessity beliefs pre-treatment, which may allow targeting of interventions to optimise adherence in these groups. Disclosure T.K.Y. Chong: None. N. Nair: None. A.W. Morgan: None. J.D. Isaacs: None. A.G. Wilson: None. K.L. Hyrich: Honoraria; Abbvie. Grants/research support; K.H has grants from BMS and Pfizer. D. Plant: None. A. Barton: Grants/research support; A.B has received funding/speaker fees from BMS, Pfizer and Galapagos.

E058 Disease activity measurement in rheumatoid arthritis - simpler in not always better!

Abstract Background/Aims Rheumatoid arthritis is one of the commonest inflammatory arthritis (1). The traditional method of disease activity assessment would incorporate activity measures like DAS 28, CDAI and SDAI which have been validated in clinical research (2). All these indices use 28 joint assessment method. These measures use different aspects of disease activity including swollen joint count, tender joint count, patient global scores and physician global assessment scores and inflammatory markers are included in some of the measures. We conducted a small study to compare these outcome measures in patients with moderate RA (per DAS criteria) who were recruited for disease activity assessment through MSK ultrasound. Methods Of the 30 biologic naive patients recruited, 27 were included in this study. Patients with moderate disease activity (per DAS criteria) were recruited for MSK ultrasound evaluation by a single rheumatologist. Patients with a diagnosis of fibromyalgia were excluded. These patients had been reviewed by two assessors prior to USS assessment and disease activity measures updated. Patient data was collected through electronic patient records. Data was analysed through MS Excel. Results The median age was 63. There were 66% females and 34% male patients. Majority were sero positive for either RhF, Anti CCP or both (77%). Mean DAS-28 score was 4.4 and corresponding mean CDAI and SDAI scores were 22.8 and 23.5 respectively. Mean HAQ score 1.08 and median CRP was 8.6. The median composite EULAR OMERACT synovitis score was 9.18. The average physician global assessment score for disease activity before USS was 4.9/10 and it correlated well with decision to escalate treatment in 41% patients as a result of USS assessment. Conclusion With a small sample size, this project shows that simplified disease activity measures do not necessarily provide clear evidence of disease activity and are heavily influenced by patient reported outcome measures (tender joint count and global pain scores). CDAI scores can be slightly higher compared to DAS and SDAI scores for the similar patients. Physician assessment and ultrasound can provide robust evaluation of disease activity and help in decision-making. A multicentric study with a large simple size to evaluate these findings would be helpful. Judicious use of clinical evaluation and imaging can help in tailoring treatment according to patient’s clinical condition and can also save money. Disclosure H. Crawshaw: None. E. Gates: None. C. Acebes: None. M. Jamal: None.

P173 The positive utility of PSAID-12 score in remote monitoring and the impact of gender and treatment on patient reported outcomes in psoriatic arthritis

Abstract Background/Aims Psoriatic arthritis (PsA) is a chronic inflammatory disease that significantly impacts the quality of life (QOL) of patients. The PSAID-12 score reflects the impact of the PsA from the perspective of the patients. This study assessed patient reported outcomes using the PSAID-12 and evaluated the impact of gender, treatment and disease duration. Methods This study was a cross-sectional, observational study of patients with PsA meeting CASPAR critieria. Patients were recruited consecutively from clinic and completed the PSAID-12 questionnaires 14 days prior to their clinic visit digitally or by paper. Demographic and clinical data, including age, gender, disease duration, medication were collected. Disease activity was measured using the the tender/swollen joint count, patient/physician assessment and CRP. Results The total number of patients in the study was n = 225. The female:male ratio was 1.0:0.8. The mean disease duration was 27 years (range 2 months to 44 years). The mean age was 52 years (range 18 to 86 years). The number of patients on DMARDs was 89.3 % (201/225) and combined DMARDs and biologics was 26.67 % (60/ 225). The mean PSAID-12 score was 4.09 (SD 2.47). There was a positive correlation between the pre-clinic PSAID-12 score and the in-person calculated tender joint count (r = 0.58), swollen joint count (r = 0.51) and the Likert pain score (r = 0.84). All domains of the PsAID-12 score were higher in female than male (4.53 vs 3.47 respectively), Table 1. Fatigue, discomfort, and pain were the most reported score for females (mean 5.52, 5.22, 5.02 respectively) whereas for males the commonest scores were discomfort, pain and fatigue (mean 4.10, 3.88, 3.88 respectively). The fourth commonest score for both genders was the impact on work and or leisure activities (4.67 for females and 3.83 for males). In terms of disease duration, discomfort is the most common reported score for patients with a disease duration of less than 5 years (mean 5.09) whereas fatigue was the most common complaint in patients with the group of 5-10 years and >10 years (4.56 and 5.11 respectively). There was a lower mean score of skin problems in the biologics compared to the non-biologic group (2.78 vs 3.90). There was a trend towards lower coping, embarrassment, and social participation scores in the biologics group. Conclusion The PSAID-12 score correlated well with PsA disease activity. The impact on QOL from PsA was higher in females than males. Fatigue, pain and discomfort were the commonest symptoms and higher scores were reported in early disease, with discomfort being the highest in this group. Fatigue was more commonly reported in patients with longer disease duration. The benefits of the biologics on QOL and skin problems were seen in these patients despite their longer disease duration. Disclosure A. Chan: None. N. Soe: None.

Drug survival and change of disease activity using a second janus kinase inhibitor in patients with difficult-to-treat rheumatoid arthritis who failed to a janus kinase inhibitor and subsequent biologics.

To assess the drug survival and change of disease activity using a second Janus kinase inhibitor (JAKi) after failure to a JAKi and subsequent biologic disease-modifying anti-rheumatic drugs (bDMARDs) in patients with difficult-to-treat rheumatoid arthritis (RA). This retrospective cohort study included 32 patients with difficult-to-treat RA who failed to a JAKi and subsequently to one or more bDMARDs and then switched to a second JAKi. To assess drug survival, electronic medical records of each patient were reviewed. Data on whether the second JAKi was discontinued, and the reasons for discontinuation were collected. The change of disease activity was assessed by analyzing changes in tender joint count (TJC), swollen joint count (SJC), patient's global assessment of disease activity on a visual-analogue scale (VAS), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), Disease Activity Score for 28 joints with ESR (DAS28-ESR), and DAS28-CRP from baseline to that at six months from initiation of the second JAKi. Overall, discontinuation of the second JAKi occurred in 20 (62.5%) patients. Primary failure, secondary failure, adverse events, and insurance coverage issues were the reasons for discontinuation in 9 (45.0%), 5 (25.0%), 2 (10.0%), and 4 (20.0%) patients, respectively. The estimated 2-year drug survival rate was 39.3%. In terms of change of disease activity, the second JAKi significantly improved TJC (p < 0.001), SJC (p < 0.001), VAS (p < 0.001), CRP (p = 0.026), DAS28-ESR (p < 0.001), and DAS28-CRP (p < 0.001) at 6-month compared with that at the baseline. Second JAKi could be a therapeutic option in patients with difficult-to-treat RA who have failed to a JAKi and subsequent bDMARDs.

Sleep disorders in rheumatoid arthritis patients

Aim of the workTo determine the frequency of sleep disturbances in patients with rheumatoid arthritis (RA) and to identify associated factors. Patients and methodsThis study included 100 RA patients. The disease activity score (DAS28), tender joint count (TJC), swollen joint count (SJC), Visual Analog Scale (VAS)-pain and Health Assessment Questionnaire (HAQ) were assessed. Epworth Sleepiness Scale (ESS) and Pittsburgh Sleep Quality Index (PSQI) were used to assess sleep quality. ResultsThe patients were 89 females and 11 males, mean age 53.2 ± 11.2 years (21–76 years) and disease duration was 11.1 ± 8.9 years (1–40 years).The meanTJC was 8.5 ± 7.9 (0–24), SJC 4 ± 4.8 (0–24) and VAS 51 ± 21 mm (10–90 mm). Their mean DAS28 was 3.9 ± 1.1 (1–6.15) and HAQ 1.3 ± 0.7 (0–2.9). The ESS was 7.9 ± 5.6 (0–24). 28 % of patients had signs of daytime sleepiness (ESS ≥ 11 points) with a significant association with female sex (p = 0.03), TJC (p = 0.03), SJC (p = 0.02), DAS28 (p = 0.05), VAS (p = 0.04) and HAQ (p < 0.01). The mean Pittsburgh score was 6.9 ± 5.1 (0–19). 51 % of patients had disturbed sleep (PSQI > 5.5 points). The most disturbed components were respectively sleep latency (1.5 ± 1.1), subjective sleep quality (1.25 ± 0.8) and sleep disorders (1.19 ± 0.8). Disturbed sleep assessed by PSQI had a significant association with TJC (p < 0.01), SJC (p < 0.01), C-reactive protein, nocturnal awakening (p < 0.01), DAS28 (p < 0.01), VAS-pain (p < 0.01), HAQ (p < 0.01), and corticosteroid intake (p = 0.01). ConclusionHalf of the patients had sleep disorders with a significant association with disease activity parameters which underline the importance of ensuring remission or low level of activity to improve the quality of sleep of patients.

Depression in Rheumatoid Arthritis: Prevalence and Effects on Disease Activity.

Background:The primary objective of this study was to estimate depression's prevalence in a cohort of rheumatoid arthritis (RA) patients, and the secondary objective was to evaluate the impact of depression on disease activity over time. Methods: We included all patients with RA presenting to our clinic from 2019 to 2020, who had three follow-up visits available. Depression prevalence was calculated using the patient's history of diagnosed depression, and disease activity was assessed using the disease activity score for 28 joints (DAS28) and its components: tender joint count (TJC), swollen joint count (SJC), pain value on a visual analog scale (VAS), and inflammatory markers. Results: A total of 400 RA patients were included, 75 of whom had diagnosed depression, generating a prevalence of 18.8%. The mean values of DAS28 and its components were higher, with statistical significance, in the depression subgroup at all three follow-ups (p < 0.001). Conclusions: Depression is prevalent in the RA population, and leads to higher disease activity in dynamic evaluations. Assessing depression could be a psychological marker for RA prognosis with an important outcome in controlling disease activity.

Effect of Periodontal Therapy on Rheumatoid Disease Activity in Patients on Anti-Rheumatoid Drugs - A Prospective Study.

The aim of this clinical trial rheumatoid arthritis-chronic periodontitis (RA-CP) is to assess the effect of non-surgical periodontal therapy in RA patients. Sixty RA patients taking disease-modifying anti-rheumatoid drugs (DMARD) with CP were selected from the Institute of Rheumatology, Madras Medical College, randomised into the intervention group (IG) and control group (CG). IG received non-surgical periodontal therapy after the screening visit, but CG did not receive treatment until the 3 months study period. Periodontal parameters were recorded at baseline and after 3 months for both groups. Rheumatoid Disease activity (RD activity) was assessed using disease activity score (DAS28), inclusive of tender joints count (TJC), swollen joints count (SJC), visual analog scale (VAS), and erythrocyte sedimentation rate (ESR) for both groups at baseline and after 3 months. At the end of 3 months, IG had significant reduction in RA parameters such as tender joints count (0.0005), swollen joints count (0.0005), ESR (0.003), VAS score (0.0005), and DAS28 values (0.0005) compared to CG. Periodontal parameters at the end of 3 months were also significantly reduced in IG than in CG. Non-surgical periodontal therapy might have reduced the burden of systemic inflammatory markers, thus reducing severity of RA in IG. Reduction in tenderness and swelling of joints in the upper arm might have enabled the patients in IG to perform better oral hygiene maintenance procedures.

Evaluating the real-world effectiveness of belimumab in patients with SLE using SLE-related laboratory values and rheumatoid arthritis-derived disease activity measures: RAPID3, swollen joint count and tender joint count

ObjectiveTo investigate the real-world impact of intravenous belimumab treatment among patients with SLE using rheumatoid arthritis-derived disease activity measures and SLE-related laboratory values.MethodsThis retrospective cohort study used US electronic medical...

Investigation of recurrence of joint symptoms after COVID-19 in patients with rheumatoid arthritis: Cross-sectional study

Abstract Background: In this study, the relationship between involvement by COVID-19 and the recurrence of symptoms of rheumatoid arthritis (RA) was investigated. Materials and Methods: This cross-sectional study was conducted on 112 patients with RA with and without a history of COVID-19. The severity and recurrence of RA symptoms were measured and recorded by the Disease Activity Score in 28 joints (DAS-28) index and clinical evaluations by a rheumatologist. Results: The results showed that the recurrence of RA in patients with and without a history of COVID-19 had a statistically significant difference (P &lt; 0.001). In addition, there was a statistically significant relationship between erythrocyte sedimentation rate, visual analogue scale (VAS), tender joint count, swollen joint count, and DAS-28 and the history of COVID-19 (P &lt; 0.05). Conclusion: The present study showed that infection with COVID-19 leads to the recurrence of joint symptoms in RA patients.

Impact of DMARD treatment and systemic inflammation on all-cause mortality in patients with rheumatoid arthritis and interstitial lung disease: a cohort study from the German RABBIT register

ObjectivesTo investigate the impact of disease activity and treatment with disease-modifying antirheumatic drugs (DMARDs) on all-cause mortality in patients with rheumatoid arthritis and prevalent interstitial lung disease (RA-ILD).MethodsPatients with RA-ILD...

A Systematic Review of the Novel Targeted Immunobiological Medications in Rheumatoid Arthritis: Efficacy, Safety, and Innovation

Introduction: Over the last half-century, the treatment and management of autoimmune rheumatic diseases have progressively improved, particularly with the contribution of immunobiological or biological therapies known as disease-modifying antirheumatic drugs. Although these agents have been generally efficient in the management of rheumatoid arthritis (RA), some patients experience limited efficacy and non-responsiveness to treatment. In addition, they may cause adverse clinical effects, further aggravating the disease. Objectives: Despite advancements in biological therapies, significant clinical needs persist. This review aims to discuss novel treatments, guiding future guidelines and drug discoveries for rheumatoid arthritis. Methods: This review follows the 2020 PRISMA statement, utilising PubMed and Google Scholar for literature search and emphasizing recent meta-analyses on the safety and efficacy of targeted immunobiological medications. Results: Small molecule inhibitors, whether utilised independently or in conjunction with Methotrexate, have been shown to contribute to effective disease management and have the potential for better adherence to the American College of Rheumatology criteria. Tocilizumab therapy demonstrates a significant reduction in disease activity and improves rates of disease remission when combined with Methotrexate. Investigations of mesenchymal stromal cell therapies have had promising outcomes, improving both cartilage quality (as evaluated by Macroscopic Cartilage Repair Assessment) and joint tenderness and swelling in clinical joint counts. Intra-articular administration of tolerogenic dendritic cells has displayed a capacity to alleviate pain, as measured by Visual Analog Scale scores, and enhance the Disease Activity Score across 28 joints. Resveratrol capsules supplemented with allopathic therapy show potential in reducing TNF-α and interleukin-6 serum levels. Conclusion: More investigations and their analysis will improve patient outcomes and reduce adverse effects and the costs involved in developing and obtaining immunobiological drugs. Moreover, assessing the safety and efficacy of anti-RA properties of the bioactive compounds could offer less toxic and more cost-effective natural treatment options.

Prognostic modeling in early rheumatoid arthritis: reconsidering the predictive role of disease activity scores.

In this prospective cohort study, we provide several prognostic models to predict functional status as measured by the modified Health Assessment Questionnaire (mHAQ). The early adoption of the treat-to-target strategy in this cohort offered a unique opportunity to identify predictive factors using longitudinal data across 20years. A cohort of 397 patients with early RA was used to develop statistical models to predict mHAQ score measured at baseline, 12months, and 18months post diagnosis, as well as serially measured mHAQ. Demographic data, clinical measures, autoantibodies, medication use, comorbid conditions, and baseline mHAQ were considered as predictors. The discriminative performance of models was comparable to previous work, with an area under the receiver operator curve ranging from 0.64 to 0.88. The most consistent predictive variable was baseline mHAQ. Patient-reported outcomes including early morning stiffness, tender joint count (TJC), fatigue, pain, and patient global assessment were positively predictive of a higher mHAQ at baseline and longitudinally, as was the physician global assessment and C-reactive protein. When considering future function, a higher TJC predicted persistent disability while a higher swollen joint count predicted functional improvements with treatment. In our study of mHAQ prediction in RA patients receiving treat-to-target therapy, patient-reported outcomes were most consistently predictive of function. Patients with high disease activity due predominantly to tenderness scores rather than swelling may benefit from less aggressive treatment escalation and an emphasis on non-pharmacological therapies, allowing for a more personalized approach to treatment. Key Points •Long-term use of the treat-to-target strategy in this patient cohort offers a unique opportunity to develop prognostic models for functional outcomes using extensive longitudinal data. •Patient reported outcomes were more consistent predictors of function than traditional prognostic markers. •Tender joint count and swollen joint count had discordant relationships with future function, adding weight to the possibility that disease activity may better guide treatment when the components are considered separately.

Real-Life Comparison of Four JAK Inhibitors in Rheumatoid Arthritis (ELECTRA-i Study).

Background: Real-world evidence of the efficacy and adverse events of JAK inhibitor treatment (Tofacitinib, Baricitinib, Upadacitinib, and Filgotinib) in rheumatoid arthritis is still limited. Methods: We studied 115 patients from the Rheumatology Unit of S. Giovanni di Dio Hospital affected by D2T-RA, according to the 2010 EULAR criteria. Out of the 115 patients, 17 had been treated with Baricitinib 8 mg/daily, 32 with Filgotinib 200 mg/daily, 21 with Tofacitinib 10 mg/daily, and 45 with Upadacitinib 15 mg/daily. We evaluated the clinical response after 3, 6, and 12 months of treatment and the follow-up from September 2022 to September 2023. All patients were evaluated according to the number of tender joints (NTJs), number of swollen joints (NSJs), visual analog scale (VAS), global assessment (GA), health assessment questionnaire (HAQ), Disease Activity Score (DAS28), and CDAI. Furthermore, laboratory parameters of efficacy and tolerability were evaluated. Results: All treatments demonstrated a statistically significant decrease in the DAS28 and CDAI scores, tender and swollen joint counts, VAS, HAQ, and patient global assessment (PGA) after 3, 6, and 12 months of treatment. All treatments showed similar behavior, and statistically significant decreases in circulating calprotectin, TNFα, and IL-6 were observed for all drugs after 12 months of treatment. In addition, soluble urokinase plasminogen activator receptor (suPAR) values showed significant differences at baseline and after 12 months of treatment for Filgotinib: 4.87 ± 4.53 vs. 3.61 ± 0.9 (0.009) and Upadacitinib: 6.64 ± 7.12 vs. 4.06 ± 3.61 (0.0003), while no statistically significant differences were found for Baricitinib: 3.4 ± 0.1 vs. 3.78 ± 0.1 and Tofacitinib: 3.95 ± 1.77 vs. 2.58 ± 0.1. The TC/HDL-C ratio (atherogenic index) showed significant differences when comparing Baricitinib vs. Filgotinib (0.0012), Filgotinib vs. Tofacitinib (0.0095), and Filgotinib vs. Upadacitinib (0.0001); furthermore, the LDL-C/HDL-C ratio in the Filgotinib group did not change (2.37 ± 0.45 vs. 2.35 ± 2.13 (NS)) after 12 months of treatment. Venous Thrombotic Events (VTEs) and major adverse cardiovascular events (MACEs) accounted for 1% of adverse events after treatment with Baricitinib. Herpes zoster reactivation accounted for 1% of adverse events after treatment with Filgotinib and Tofacitinib, while non-melanoma skin cancer (NMSC) accounted for 1% of adverse events after Upadacitinib treatment. Conclusions: Our real-world data from patients with RA show differences in some laboratory parameters and in the impact of lipid metabolism in JAK inhibitor treatment.

Analysis of the Effect of Rehabilitation Nursing Intervention on Functional Recovery in Patients with Rheumatoid Arthritis

Objective: To explore and analyze the effect of rehabilitation nursing intervention on functional recovery in patients with rheumatoid arthritis. Methods: From May 2020 to May 2023, 150 patients with rheumatoid arthritis who received integrated treatment of Tibetan and Western medicine in the rheumatology department were selected as the research subjects. They were divided into the rehabilitation group and the reference group according to the double-blind mechanism, with 75 cases in each group. The rehabilitation group received rehabilitation nursing intervention and the reference group received basic nursing. The standard of living, joint function recovery, and nursing satisfaction were compared between the two groups. Results: Before the intervention, there was no statistically significant difference (P &gt; 0.05) in living standards such as physiology, mental outlook, emotional performance, and social culture between the groups. After the intervention, the standard of living such as culture, of the rehabilitation group was significantly better than that of the reference group (P &lt; 0.05). Before the intervention, there was no statistically significant difference (P &gt; 0.05) in the recovery of joint functions such as the number of joint tenderness, grip strength of both hands, duration of morning stiffness, and number of joint swelling among the groups. After the intervention, the number of joint tenderness, hand grip strength, duration of morning stiffness, number of joint swelling, and other joint function recovery in the rehabilitation group were significantly better than those in the reference group (P &lt; 0.05). The nursing satisfaction of the rehabilitation group was significantly higher than that of the reference group (P &lt; 0.05). Conclusion: Rehabilitation nursing intervention can accelerate the recovery of joint function and improve the living standard of patients with rheumatoid arthritis.

Early Oligoarticular Psoriatic Arthritis Responds to Treatment With Apremilast: Week 16 Results From FOREMOST - a Phase 4 Randomized Controlled Trial

Early Oligoarticular Psoriatic Arthritis Responds to Treatment With Apremilast: Week 16 Results From FOREMOST – a Phase 4 Randomized Controlled Trial&#x0D; Laure Gossec1, Dafna Gladman2, Laura C. Coates3, Jacob Aelion4, Jitendra Vasandani5, Jyotsna Reddy6, Rebecca Wang6, Michele Brunori6, Stephen Colgan6, Philip Mease7&#x0D; 1Sorbonne Université and Pitié Salpêtrière Hospital, Paris, France; 2Toronto Western Hospital, Toronto, ON, Canada; 3University of Oxford, Oxford, UK; 4West Tennessee Research Institute, Jackson, TN, USA; 5West Texas Clinical Research, Lubbock, TX, USA; 6Amgen Inc., Thousand Oaks, CA, USA; 7Swedish Medical Center/Providence St. Joseph Health and University of Washington School of Medicine, Seattle, WA, USA&#x0D; Introduction &amp; Objectives:&#x0D; Psoriatic arthritis (PsA) is underdiagnosed in dermatology practice, typically presenting 10 years after skin symptoms. Dermatologists may encounter early PsA since up to 30% of patients with psoriasis have PsA. Oligoarticular PsA affects ≤4 joints, is very common, and is underrepresented in clinical trials as most pivotal studies exclude patients with &lt;3 swollen and tender joints. Here, we report the efficacy and safety of apremilast vs. placebo for the treatment of early oligoarticular PsA.&#x0D; Materials &amp; Methods:&#x0D; FOREMOST (NCT03747939) is a phase 4, multicenter, randomized, double-blind, placebo-controlled, parallel-group study. Patients with PsA,based on CAPSAR criteria, duration ≤5 years, swollen joint count (SJC) &gt;1 but ≤4, and tender joint count (TJC) &gt;1 but ≤4 were randomized 2:1 to apremilast 30 mg BID (APR) or placebo for 24 weeks. The primary endpoint was the achievement of minimal disease activity (MDA)-Joints1 (mandating SJC ≤1 and TJC ≤1, and 3/5 alternate items) at week 16.&#x0D; Results:&#x0D; Of 308 patients randomized (APR: n=203; placebo: n=105), mean PsA duration was 9.9 months, mean age was 50.9 years, and 39.9% of patients were using csDMARD. MDA-Joints response was achieved in 33.9% vs. 16.0% for patients treated with APR vs. placebo (primary endpoint, P=0.0008). At week 16, a significantly greater proportion, 70.2%, of patients treated with APR achieved cDAPSA REM/LDA vs. 51.8% with placebo (P=0.0017). A greater proportion of patients achieved a good/moderate response in PASDAS score with APR (59.9%) vs. placebo (42.7%). Greater improvements from baseline in PsA Impact of Disease (PsAID)-12 score (LS mean change, −1.5 vs. −0.4; nominal P&lt;0.0001) and nail psoriasis score (visual analog scale [VAS]; LS mean change, −13.9 vs. −6.8; nominal P=0.0094) were observed with APR vs. placebo at week 16. Patients treated with APR also achieved greater improvement in quality of life measures (Patient Pain [VAS ≤15: 59.6 vs. 13.8; nominal P=0.0022], Patient Global Assessment [PtGA; VAS ≤20: 61.7 vs. 20.1; nominal P=0.0286]) when compared to placebo at week 16. No new safety signals were identified.&#x0D; Conclusion:&#x0D; FOREMOST is the first global randomized controlled trial exclusively studying early oligoarticular PsA. We report the first results of FOREMOST, the primary outcome, and show better disease control is achievable with APR, with twice the MDA-Joint response compared with placebo at 16 weeks. These findings show APR treatment of early oligoarticular PsA improves clinical and quality of life outcomes and may inform optimal management of these patients.&#x0D; Reference: 1. Coates LC, et al. J Rheumatol. 2016;43:371–5.

Clinical observation of hypofibrinogenemia induced by the treatment of tocilizumab in rheumatic diseases and exploration of risk factor for hypofibrinogenemia.

The objective of this study was to analyze the changes in plasma fibrinogen (FIB) levels during tocilizumab (TCZ) treatment in patients with rheumatic diseases, to clarify the incidence of hypofibrinogenemia and its possible risk factors, and toestablish a nomogram model for predicting the probability of hypofibrinogenemia in rheumatoid arthritis (RA) patients treated with TCZ. Clinical data of patients treated with TCZ at the Department of Rheumatology and Immunology, the First Affiliated Hospital of Xi'an Jiaotong University from January 2014 to October 2021 were retrospectively analyzed to observe the incidence of hypofibrinogenemia in several rheumatic diseases at different time points. The risk factor of hypofibrinogenemia in RA patients treated with TCZ was determined by using Cox regression analysis. Based on the results of Cox regression analysis, a nomogram for predicting the probability of hypofibrinogenemia in rheumatoid arthritis (RA) patients treated with TCZ was established and validated through RStudio software. A total of 83 TCZ-treated patients were enrolled in this study, and 32 (38.55%) patients developed hypofibrinogenemia during TCZ treatment. There were 8 males and 24 females in the FIB-reduced group, with an average age of 44.88 ± 18.39years. Hypofibrinogenemia was most common in TCZ-treated patients with takayasu arteritis (TA) and RA. Hypofibrinogenemia typically occured within 3months after TCZ treatment. In RA patients treated with TCZ, platelet distribution width, parathyroid hormone, bone mineral density, tender joint count, and swollen joint count were independent risk factors for the occurrence of hypofibrinogenemia. The nomogram based on the above risk factors could effectively predict the probability of hypofibrinogenemia in RA patients receiving TCZ. Although bleeding symptoms were not observed in this study, the incidence of hypofibrinogenemia remained high after TCZ treatment, usually occurring within 3months of treatment. Therefore, it is necessary to monitor FIB levels during TCZ treatment. In addition, clinicians can use the nomogram model developed from this study to predict the incidence of hypofibrinogenemia after TCZ treatment in RA patients. Key Points • Hypofibrinogenemia often occurs during TCZ treatment for rheumatic diseases. • PDW, PTH, BMD, tender joint count, and swollen joint count are risk factors for the occurrence of hypofibrinogenemia. • It is necessary to monitor FIB levels during TCZ treatment to avoid bleeding tendency.

Efficacy and safety of Huzhang Granule, a compound Chinese herbal medicine, for acute gouty arthritis: A double-blind, randomized controlled trial

BackgroundAcute gouty arthritis (AGA) is an inflammatory joint disease with a high prevalence. Typical medical interventions, including nonsteroidal anti-inflammatory drugs, colchicine and glucocorticoids, can have serious adverse reactions. Huzhang Granule (HZG), a compound Chinese herbal medicine, has been used to treat AGA for more than 30 years with satisfactory effects and no significant adverse reactions. However, the efficacy and safety of HZG in AGA patients remains unknown. ObjectiveThe present investigation was designed to examine the efficacy and safety profile of HZG in managing AGA patients. Design, setting, participants and interventionsThe current study was conducted as a noninferiority, randomized controlled clinical trial on 180 eligible enrolled participants. Participants were randomly assigned into the HZG and etoricoxib groups. Treatments were administered for 5 d, during which the HZG group received HZG and placebo etoricoxib, while the etoricoxib group received etoricoxib and placebo HZG in the same ratio (1:1). Main outcome measuresThe primary outcome was pain experienced by the patient in the gout-afflicted joint from days 2 to 5 of the treatment window. The pain level was measured via a visual analogue scale, ranging from 0 mm to 100 mm. The secondary outcomes comprised joint tenderness and swelling, reduction of inflammatory biomarkers, and the patient’s and investigator’s global evaluations of therapeutic response. ResultsThe mean reduction in pain was −51.22 mm (95% confidence interval [CI], [−53.42, −49.03] mm) for the HZG and −52.00 mm (95% CI, [−54.06, −49.94] mm) for the etoricoxib groups. The mean difference between the two groups was 0.78 mm (95% CI, [−2.25, 3.81] mm). All additional efficacy endpoints, covering decreased inflammation and pain relief, yielded compelling proof of noninferiority. Patients in the HZG group exhibited a comparatively lower rate of adverse events compared to those in the etoricoxib group (4.44% vs 13.33%; P ≤ 0.05). ConclusionHZG and etoricoxib groups demonstrated similar levels of analgesic effectiveness. The safety and efficacy of HZG indicates that it can be used as a potential therapeutic option for treating AGA. Trial registrationChinese Clinical Trial Registry (ChiCTR2000036970).Please cite this article as: Wang H, Chen ST, Ding XJ, Kuai L, Hua L, Li X, Wang YF, Zhang M, Li B, Wang RP, Zhou M. Efficacy and safety of Huzhang Granule, a compound Chinese herbal medicine, for acute gouty arthritis: A double-blind, randomized controlled trial. J Integr Med. 2024; 22(3): 270–278.

BASDAI versus ASDAS in evaluating axial involvement in patients with psoriatic arthritis: a pooled analysis of two phase 3 studies.

In the absence of axial psoriatic arthritis (axPsA)-specific tools, the BASDAI and Ankylosing Spondylitis Disease Activity Score (ASDAS) are used to assess axial symptoms in patients with PsA. Here, we assessed the performance of BASDAI and ASDAS in patients with PsA. Patients with active PsA in DISCOVER-1 and DISCOVER-2 (ClinicalTrials.gov: NCT03162796 and NCT03158285, respectively) with or without axPsA but with available baseline BASDAI information were analysed; those with investigator-identified axial symptoms and imaging-confirmed sacroiliitis comprised the axPsA cohort. Correlations between BASDAI/ASDAS and clinical variables were assessed with Pearson's coefficient (r). Longitudinal effects of enthesitis (Leeds Enthesitis Index [LEI]), swollen joint count and presence versus absence of axPsA on BASDAI/ASDAS (normalized 0-10 scale) were analysed with mixed models for repeated measures. At baseline in the axPsA (n = 312) and non-axPsA (n = 124) cohorts, BASDAI scores showed no or weak correlation with swollen joint count (0.18-0.20), tender joint count (0.12-0.29), LEI (-0.04 to 0.24) and physician global assessment (0.35-0.43); moderate correlation with fatigue (both -0.56); and strong correlation with patient global assessment of disease activity (0.62-0.69) and patient-reported pain (0.66-0.70). Similar correlations were observed for ASDAS. Axial involvement versus non-involvement was associated with higher BASDAI scores and ASDAS (all β ≥ 0.5), without differences between instruments; longitudinal associations between swollen joint count (β ≤ 0.06)/LEI (β ≤ 0.19) and BASDAI/ASDAS were clinically unimportant. BASDAI and ASDAS performed similarly in patients with active PsA and axial involvement, independent of peripheral disease involvement, supporting their performance in assessing axial disease activity. ClinicalTrials.gov, http://clinicaltrials.gov, NCT03162796 and NCT03158285.

Microstructural abnormality of white matter tracts in rheumatoid arthritis

BackgroundStructural and functional brain imaging studies have reported abnormalities of gray matter morphology and functional activities in patients with rheumatoid arthritis (RA). However, it is largely unknown whether patients with RA show alterations of white matter microstructural organization. ObjectivesTo automatically identify alteration of white matter microstructure in patients with RA and further examine how this alteration associates with clinical characteristics. MethodsThis single-institutional prospective study included 66 participants (33 patients with RA [52 ± 9 years, 29 women] and 33 sex/age-matched healthy controls [53 ± 12 years, 27 women]), who underwent diffusion MRI scan from January 2021 to December 2021. The white matter microstructure was assessed using fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity. Voxelwise analyses were conducted on white matter skeleton using an automated, observer-independent tract-based spatial statistics analysis. The relationship between white matter microstructural alterations and clinical and neuropsychological variables was evaluated using correlation analysis. ResultsCompared with healthy controls, patients with RA exhibited lower fractional anisotropy in several major white matter tracts (threshold-free cluster enhancement at P < 0.05 for multiple comparison correction, permutation test), involving the forceps minor, bilateral inferior fronto-occipital fasciculus, bilateral anterior thalamic radiation, and bilateral uncinate fasciculus. Lower fractional anisotropy values in the patients with RA were significantly associated with pain-related assessments, including tender joint count (r = -0.43, P = 0.015), Clinical Disease Activity Index score (r = -0.36, P = 0.049), pain severity rated through visual analogue scale (r = -0.45, P = 0.012), and Simplified Disease Activity Index score (r = -0.36, P = 0.045). No significant group difference was found in mean diffusivity, axial diffusivity, and radial diffusivity. ConclusionsWe report the first anatomical evidence for aberrant microstructure organization of several major white matter tracts and its associations with pain processing in patients with rheumatoid arthritis.