American College Of Rheumatology Criteria Research Articles

Biology of tongue coating in different disease stages of RA and its value in disease progression

ObjectiveTo assess and compare the composition of tongue coating microbiota among patients at different stages of rheumatoid arthritis (RA). MethodsA total of 47 patients diagnosed with RA, as per the American College of Rheumatology criteria, and 10 healthy individuals were enrolled in this study. The RA patients were stratified considering their Disease Activity Score 28 (DAS28), a composite measure based on the 28 tender and swollen joint count and erythrocyte sedimentation rate (ESR). The study population was further categorized into active phase group (LMH group) and inactive phase group (RE group) according to their DAS28 values. DNA extraction was extracted from tongue coating samples. Subsequently, the V3–V4 16S rDNA region was selectively amplified and sequenced through high-throughput 16S rDNA analysis. The resulting data were then utilized to ascertain the microbial contents. ResultsSignificant variations were observed in the tongue coating microbiota of patients with RA during active and inactive phases, in comparison to healthy individuals (p < 0.05). At the genus level, the presence of Prevotellan, Veillonella, Rothia, and Neisseria in RA patients was notably more evident than in the healthy control (HC) group. These disparities find support in existing research on gut and oral microbiota. During the active phase of RA, the relative abundance of Veillonella, Rothia, and Neisseria in the tongue coating microbiota of patients was significantly higher than in those with inactive RA. These findings underscore the need for further and in-depth research on the potential impact of these microorganisms on the progression of RA disease. ConclusionThe results substantiate the hypothesis that tongue coating microbes actively contribute to the progression of RA.

Exploring the association of gender role expectations of pain and measures of pain sensitization in people with knee osteoarthritis: A cross-sectional study

ObjectivesFirst, we explored the association between Gender Role Expectations of Pain (GREP), and psychophysical measures of sensitization in people with knee osteoarthritis (OA). Second, we explored whether the association differed by level of GREP items (high vs low scores). DesignWe conducted secondary analyses of a cohort study. Those who were (i) age of ≥ 40, English or French speaking, ii) diagnosed with knee OA using American College of Rheumatology criteria and iii) consulting with an orthopedic surgeon were included. GREP items pertaining to pain sensitivity and pain endurance of the typical man or woman were rated by males and females respectively. Psychophysical tests consisted of pressure pain thresholds (PPTs), Temporal Summation (TS), and Conditioned Pain Modulation (CPM). Multiple linear regression models for males and females were run with GREP scores (independent variables) and psychophysical tests (dependent variables). Next models stratified on the median split of GREP scores were run. Models were adjusted for age, BMI, pain catastrophizing, anxio-depressive symptoms, and radiographic severity. Results280 participants (57% females; age (SD): 63.9 (9.6) and BMI (SD): 31.3 (8.40)) were included. GREP pain sensitivity scores in males were associated with CPM values (β: 95% CI: 0.09 (0.01 to 0.17)). Males with low GREP pain sensitivity or pain endurance had very small to small positive associations with PPT and CPM values. ConclusionThis first exploration of gendered pain sensitivity and pain endurance by males and females has small and clinically unimportant associations with measures of pain sensitization requiring further validation.

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.

The role of the progesterone receptor PROGINS variant in the development of fibromyalgia syndrome and its psychological findings

Fibromyalgia syndrome (FMS), a chronic pain disorder of unknown etiology, is more common in women. This suggests that biological sex is important. Therefore, we performed an analysis to determine whether the progesterone receptor (P GR) gene Alu insertion (named P ROGINS) variant is associated with an increased risk of FMS in the Turkish population. A total of 288 subjects, including 138 patients diagnosed with FMS according to the 2016 American College of Rheumatology criteria and 150 healthy subjects, were evaluated. Genotyping of the P GR P ROGINS variant was determined by polymerase chain reaction (P CR) analysis. The results of the analyses were evaluated for statistical significance. There were no subjects in the control group carrying the T2 allele. The P GR P ROGINS T1/T2 genotype was more prevalent in both all patients and female patients compared to all controls and female controls (p = 0.001, p = 0.003, respectively). A statistically significant relationship was observed in both all patients and female patients when compared to the control group according to T1/T1 vs. T1/T2+T2/T2 (p < 0.000, p < 0.001, respectively). The current study suggests that the P GR Alu insertion variant T2 allele might influence FMS susceptibility in the Turkish population. Large-sample sizes and studies of different ethnicities are required to further evaluate the association between this variant and FMS.

Efficacy and Safety of Risankizumab for Active Psoriatic Arthritis: 100-Week Results from the Phase3 KEEPsAKE1 Randomized Clinical Trial.

Patients with psoriatic arthritis (PsA) require treatment providing durable long-term efficacy in different disease domains as well as safety. We present 100-week efficacy and safety results of risankizumab in patients with active PsA and previous inadequate response/intolerance to ≥ 1 conventional synthetic disease-modifying antirheumatic drug (csDMARD-IR). KEEPsAKE1 (NCT03675308) is a global phase3 study, including a 24-week, double-blind, placebo-controlled and ongoing open-label extension periods. Patients were randomized 1:1 to receive risankizumab 150mg or placebo at baseline and weeks4 and 16. After week24, all patients received open-label risankizumab every 12weeks thereafter. Patients were evaluated through 100weeks. Endpoints included achieving ≥ 20% reduction in American College of Rheumatology criteria for symptoms of rheumatoid arthritis (ACR20), minimal disease activity (MDA; defined as ≥ 5/7 criteria of low disease activity and extent), and other measures. Overall, 828/964 (85.9%) patients completed week100. For patients receiving continuous risankizumab, 57.3%, 70.6%, and 64.3% achieved ACR20 at weeks24, 52, and 100, respectively. For the placebo/risankizumab cohort, 33.5% achieved ACR20 at week24 but increased after switching to active treatment at weeks52 (63.7%) and 100 (62.1%). In ACR20 responders at week52, 81.2% of both treatment cohorts maintained response at week100. MDA was achieved by 25.0%, 38.3%, and 38.2% of the continuous risankizumab cohort at weeks24, 52, and 100. In the placebo/risankizumab cohort, 10.2% achieved MDA at week24, increasing at weeks52 (28.0%) and 100 (35.2%). MDA response was maintained at week100 in week52 responders in the continuous risankizumab (75.5%) and placebo/risankizumab cohorts (78.2%). Similar trends were observed for other efficacy measures. Risankizumab was generally well tolerated through 100weeks. For patients with active PsA who are csDMARD-IR, risankizumab demonstrated durable long-term efficacy and was generally well tolerated, with a consistent long-term safety profile. ClinicalTrials.gov identifier, NCT03675308.

Efficacy and Safety of Risankizumab for Active Psoriatic Arthritis: 100-Week Results from the KEEPsAKE2 Randomized Clinical Trial.

Long-term therapeutic options providing durable response and tolerability are needed for psoriatic arthritis (PsA). The ongoing KEEPsAKE2 trial is evaluating risankizumab treatment in patients with active PsA who previously had inadequate response/intolerance to ≥ 1 conventional synthetic disease-modifying antirheumatic drug (csDMARD-IR) and/or 1-2 biologic DMARDs (bDMARD-IR). Herein, we report results through 100weeks of treatment. KEEPsAKE2 is a global phase3 trial. Patients with active PsA were randomized 1:1 to double-blind subcutaneous risankizumab 150mg or placebo (weeks0, 4, and 16). At week24, all patients received open-label risankizumab every 12weeks until end of study. Efficacy endpoints included achieving ≥ 20% improvement in PsA symptoms using American College of Rheumatology criteria (ACR20), attaining minimal disease activity (MDA; meeting ≥ 5/7 criteria of low disease activity and extent), and improving in other measures. At the cutoff date, 345/443 (77.9%) patients were ongoing in thestudy. ACR20 was achieved in 57.1% and 52.5% of the continuous risankizumab and placebo/risankizumab cohorts, respectively, at week100 and in 60.0% and 55.8%, respectively, at week52. In week52 responders, maintenance of ACR20 at week100 was achieved in 74.8% (continuous risankizumab) and 78.7% (placebo/risankizumab) of patients. In the continuous risankizumab and placebo/risankizumab cohorts, respectively, MDA was achieved by 33.0% and 33.3% of patients at week100 and by 27.2% and 33.8% at week52. Among MDA responders at week52, maintenance of MDA response was achieved by 83.6% and 73.0% of the continuous risankizumab and placebo/risankizumab cohorts, respectively. Risankizumab was well tolerated through week100. Risankizumab demonstrated durable efficacy and tolerability through 100weeks; most patients who achieved ACR20 and MDA responses at week52 maintained this achievement through week100. There were no new safety signals in patients who had csDMARD-IR and bDMARD-IR. ClinicalTrials.gov NCT03671148.

Modulation of Interleukin-23 Signaling With Guselkumab in Biologic-Naive Patients Versus Tumor Necrosis Factor Inhibitor-Inadequate Responders With Active Psoriatic Arthritis.

We assessed and compared immunologic differences and associations with clinical response to guselkumab, a fully human interleukin (IL)-23p19 subunit inhibitor, in participants with active psoriatic arthritis (PsA) who were biologic-naive or had inadequate response to tumor necrosis factor inhibitors (TNFi-IR). Serum biomarker levels at baseline and after treatment with guselkumab 100 mg every 8 weeks were compared between biologic-naive (n=251) and TNFi-IR (n=93) subgroups identified in the pooled DISCOVER-1/DISCOVER-2/COSMOS data set. Baseline biomarker levels determined by achievement of week 24 clinical responses (≥75%/90% improvement in Psoriasis Area and Severity Index [PASI 75/90], Investigator's Global Assessment [IGA] of psoriasis score 0/1 and ≥2-point improvement], ≥20% improvement in American College of Rheumatology criteria [ACR20]) were compared between prior treatment subgroups. Baseline IL-22, TNFα, and beta defensin-2 (BD-2) levels were significantly lower in biologic-naive than in TNFi-IR participants. With guselkumab, week 24 IL-17A, IL-17F, IL-22, serum amyloid A, C-reactive protein, IL-6, and BD-2 levels were significantly reduced from baseline in biologic-naive and TNFi-IR participants (≥1.4-fold difference, nominal P < 0.05). Clinical responders to guselkumab exhibited significantly higher baseline levels of several biomarkers than nonresponders (IL-17A, IL-17F, BD-2 in biologic-naive PASI 90 responders; IL-17A, BD-2 in TNFi-IR IGA 0/1 responders; IL-22, BD-2 in TNFi-IR PASI 90 responders [nominal P < 0.05]) and trended higher in TNFi-IR ACR20 responders. Guselkumab modulates IL-23 signaling and provides consistent pharmacodynamic effects in both biologic-naive and TNFi-IR PsA patients. Significantly elevated baseline IL-22, TNFα, and BD-2 levels and associations between baseline IL-22, IL-17A, and BD-2 levels and skin responses to guselkumab suggest greater dysregulation of IL-23/Th17 signaling in patients with TNFi-IR.

Pulmonary Manifestations of Systemic Lupus Erythematosus Among Adults in Aseer Region, Saudi Arabia.

Nearly half of the Systemic lupus erythematosus (SLE) patients develop lung involvement. The study assessed the extent of pulmonary involvement among SLE patients and to identify the associated factors in the population. This retrospective cohort study was conducted at Aseer Hospital and Khamis Myshat Hospital in the Southern region of Saudi Arabia. The study spanned from January 1, 2016, to June 3, 2023. Patient inclusion criteria encompassed individuals who received a definitive diagnosis and classification as per American College of Rheumatology criteria, while patients under 18 years of age and those with mixed connective tissue diseases were exclude. A total of 247 participants were included. 41.7% (n=103) aged 41 years and older, 95.1% (n = 235) were females. Around 10.10% had diabetes mellitus and 17.00% had hypertension and hypothyroidism. Lupus Nephritis was in 15.40%. Chest involvement was reported in 21.9%, in the form of pleuritis (6.10%), pleural effusion (4.00%), and lupus pneumonitis (4.00%), interstitial lung disease (4.00%), pulmonary embolism (3.60%) of individuals, and pulmonary hemorrhage (2.80%). The respiratory symptoms reported by SLE were; dyspnea, cough, and chest pain each having a prevalence of around 18.0%. Palpitations have a relatively high occurrence at 13.80%. Meanwhile, hemoptysis (blood coughing) has a lower prevalence of 1.20%, and fever is reported at 2.80%. Having chronic kidney disease and hypertension were significantly associated with having pulmonary involvement; (χ2=3.308, p=0.027) and (χ2=7.782, Fisher's p=0.002) respectively. The seropositivity for antiphospholipid Abs, anti-CCP, and antids-DNA were significantly associated with pulmonary involvement (χ2=3.239, =p=0.049), (χ2=4.621, Fisher's p=0.023), and (χ2=8.248, p=0.010) respectively. The study found that 21.9% of SLE patients experience chest involvement, with varying degrees of pulmonary symptoms. Factors such as chronic kidney disease, hypertension, antiphospholipid antibodies, Anti-CCP positivity, and seropositivity for Anti-dsDNA were found to be significant associations with lung involvement, contributing to our understanding of SLE.

Effect of knee pain on muscles imbalance and physical limitation in individuals with bilateral knee osteoarthritis: A comparative cross-sectional study

Objectives: When osteoarthritis (OA) affects the knee, it causes muscle imbalance and physical limitations. This study aimed to determine the impact of knee pain on quadriceps strength, hamstring length, and physical limitations in individuals with bilateral knee OA. Methods: A cross-sectional study at Khyber Teaching Hospital and Northwest General Hospital, Peshawar, included individuals aged 50–65, who met the American College of Rheumatology criteria. Subjects diagnosed with bilateral knee OA (grade II or greater on the Kellgren–Lawrence grading scale) and experiencing pain in both knees (numeric pain rating scale [NPRS] score ≥ 1) were selected through purposive sampling (n = 70). Data collection involved the NPRS, modified belt stabilizer hand-held dynamometer, active knee extension test, and Western Ontario and McMaster Universities Arthritis Index (WOMAC) Urdu version questionnaire. Measurements from both knees assessed quadriceps muscle strength, hamstring length, and physical limitations. Results: The median interquartile range (IQR) of quadricep strength for the more painful knee was 0.53 (0.36) Nm/kg and 1.35 (0.34) Nm/kg for the less painful knee showing a significant difference in quadriceps strength (P &lt; 0.01). In terms of hamstring length, the more painful knee had a median (IQR) of 29.0 (2.0) degrees whereas the less painful knee recorded 11.0 (6.0) degrees indicating a significant difference (P &lt; 0.01). Likewise, there was a significant difference in WOMAC scores between the less painful and more painful knees (P &lt; 0.01). Conclusion: This study found that individuals experiencing more knee pain demonstrated decreased quadriceps muscle strength and increased hamstring muscle tightness. In addition, those with more painful knees exhibited greater physical limitations in bilateral knee OA.

Skin Changes in Lupus Erythematosus: A Concise Review Lupus Erythematosus and Skin-demystifying the Features

Lupus erythematosus is an autoimmune disease characterised by the formation of various autoantibodies, leading to the involvement of numerous organ systems like the nervous system, renal system, and cutaneous involvement. Cutaneous involvement is the second most common manifestation after musculoskeletal involvement and can range from minor involvement to severe disabling sequelae. The type of skin manifestation can sometimes predict the underlying systemic involvement, as most patients of acute lupus erythematosus have concomitant systemic involvement in contrast to limited chronic cutaneous LE, which has a low incidence of systemic involvement. The cutaneous manifestations have been included in the Systemic Lupus International Collaborating Clinics (SLICC) and American College of Rheumatology criteria for ease in diagnosing lupus erythematosus patients. Herein, we present a review of various cutaneous manifestations seen in association with systemic lupus erythematosus (SLE) patients and their specific management, which can ease the early diagnosis of the patients and triage the patients that will need close follow-up for systemic involvement.

Performance of the 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology Classification Criteria for antineutrophil cytoplasmic antibody-associated vasculitis in previously diagnosed adult patients from Türkiye.

Objectives: This study aimed to evaluate the applicability of the new 2022 American College of Rheumatology (ACR)/European Alliance of Associations for Rheumatology (EULAR) criteria in Turkish adult patients previously diagnosed with antineutrophil cytoplasmic antibody-associated vasculitis (AAV). Patients and methods: One hundred sixty-four patients (96 males, 68 females; mean age: 49.6±14.4 years; range, 18 to 87 years) diagnosed with AAV by experienced rheumatologists between July 2016 and May 2022 were included in this retrospective cross-sectional study and reclassified based on the 1990 ACR criteria, the European Medicines Agency (EMEA) algorithm, and the 2022 ACR/EULAR criteria. For external validation, 83 patients (48 males, 35 females; mean age: 47.3±17.5 years; range, 19 to 81 years) diagnosed with immunoglobulin (Ig)A vasculitis were included. Results: One hundred twenty-six (76.8%) patients had granulomatosis with polyangiitis (GPA), 13 (7.9%) patients had eosinophilic granulomatosis with polyangiitis (EGPA), and 25 (15.2%) patients had microscopic polyangiitis (MPA). According to the criteria, the number of unclassified patients was nine (5.5%) for both the 2022 ACR/EULAR AAV classification criteria and the EMEA algorithm. The new criteria had an almost perfect agreement with the clinician's diagnosis (Cohen's kappa coefficient [κ]=0.858 for GPA, κ=0.820 for EGPA, and κ=0.847 for MPA). The kappa statistics for agreement of 2022 ACR/EULAR classification criteria with the EMEA algorithm were found 0.794 for GPA, 0.820 for EGPA, and 0.700 for MPA. None of the 83 patients diagnosed with IgA vasculitis could be classified as GPA, EGPA, or MPA using the new ACR/EULAR AAV classification criteria. Conclusion: The 2022 ACR/EULAR classification criteria for AAV showed substantial or perfect agreement with the clinical diagnosis and the EMEA algorithm.

Halo sign on temporal artery ultrasound versus temporal artery biopsy for giant cell arteritis.

Halo sign on temporal artery ultrasound versus temporal artery biopsy for giant cell arteritis.

Bimekizumab treatment in patients with active psoriatic arthritis and prior inadequate response to tumour necrosis factor inhibitors: 52-week safety and efficacy from the phase III BE COMPLETE study and its open-label extension BE VITAL

ObjectivesTo assess 52-week safety and efficacy of bimekizumab in patients with active psoriatic arthritis (PsA) and prior inadequate response/intolerance to tumour necrosis factor inhibitors.MethodsPatients completing the 16-week phase III double-blind,...

Evaluation of the Diagnostic Performance of American College of Rheumatology, EULAR, and National Institute for Health and Clinical Excellence Criteria Against Clinically Relevant Knee Osteoarthritis: Data From the CHECK Cohort.

Our objective was to evaluate the diagnostic performance of the EULAR, American College of Rheumatology (ACR), and National Institute for Health and Care Excellence (NICE) criteria by using clinical experts' diagnosis of clinically relevant knee osteoarthritis (OA) as the outcome of interest. In a previous study, we recruited clinical experts to evaluate longitudinal (5-, 8-, and 10-year follow-up) clinical and radiographic data of symptomatic knees from the Cohort Hip and Cohort Knee (CHECK) study for the presence or absence of clinically relevant OA. In the current study, ACR, EULAR, and NICE criteria were applied to the same 5-, 8-, and 10-year follow-up data; then a knee was diagnosed with OA if fulfilling the criteria at one of the three time points (F1), two of the time points (F2), or at all three time points (F3). Using clinically relevant OA as the reference standard, the sensitivity, specificity, and positive and negative predictive values for the three criteria were assessed. A total of 539 participants for a total of 833 examined knees were included. Thirty-six percent of knees were diagnosed with clinically relevant OA by experts. Sixty-seven percent to 74% of the knees received the same diagnosis (OA or non-OA) by the three criteria sets for the different definitions (F1 to F3). EULAR consistently (F1 through F3) had the highest specificity, and NICE consistently had the highest sensitivity. The diagnoses only moderately overlapped among the three criteria sets. The EULAR criteria seemed to be more suitable for study enrollment (when aimed at recruiting clinically relevant OA knees), given the highest specificities. The NICE criteria, given the highest sensitivities, could be more useful for an initial diagnosis in clinical practice.

Vatari Guggulu, Hingvashtaka Churna, and Brihat Saindhavadya Taila in the management of rheumatoid arthritis: An open-label, prospective, single-arm multi-center study

Abstract Background: Despite significant advances in the diagnosis and treatment of rheumatoid arthritis (RA), the clinical outcomes remain unsatisfactory in a significant proportion of patients. Ayurveda management for RA (Amavata) has shown promising clinical outcomes in routine clinical practice and as per published research studies. Objective: The study was designed to assess the therapeutic effect and safety of Ayurveda interventions, Vatari Guggulu (VG), Hingvashtaka Churna (HC), and Brihat Saindhavadya Taila (BS) in the management of RA. Materials and Methods: An open-label, prospective, single-arm multicenter study was conducted at Ayurveda Research Institutes in Patna, Bhubaneswar, and Guwahati with a sample size of 180 participants. Patients of any gender aged 20–60 years with clinically diagnosed RA as per the revised American College of Rheumatology criteria and willing to provide written informed consent to participate in the study were included in the study. Ayurveda interventions, VG, HC, and BS, were administered to the study participants for 12 weeks, with a follow-up at four weeks without intervention. The primary outcome measure was a change in the Disease Activity Score-28 (DAS28) from baseline. The other outcome measures included change in the Indian Health Assessment Questionnaire Disability Index score (HAQ-DI), changes in the acute phase reactants (erythrocyte sedimentation rate [ESR] and C-reactive protein [CRP]), and change in the quality of life parameters (assessed through the SF-36 questionnaire). Results: A total of 180 participants were enrolled in the study, and data of 179 participants were considered for the final analysis. A statistically significant difference was observed in the outcome parameters, such as a mean change in the DAS28 score, HAQ-DI score, SF-36 score, and ESR and CRP levels (P &lt; 0.001) after 12 weeks of treatment. The mean DAS28 score changed from 6.50 ± 0.790 at baseline to 4.21 ± 1.286 on week 16 follow-up (P &lt; 0.001). No participant withdrew from the study due to adverse events. The trial interventions were well-tolerated and safe. Conclusion: The study outcomes provide preliminary evidence of the safety and potential benefits of the Ayurveda interventions in the management of RA. Further, randomized controlled studies may be planned to generate robust evidence on the therapeutic potential of these interventions so that they can be recommended for use in routine clinical practice. Trial registration: CTRI/2014/12/005242.

Utility of sUPAR as a Novel Biomarker for Stratifying Rheumatoid Arthritis Patients in Remission

Introduction: Soluble urokinase plasminogen activator receptor (SuPAR) is a novel biomarker studied in conditions such as infections and malignancies. There is a paucity of data on suPAR levels in patients in RA clinical remission. A hypothesis-driven study was conducted to determine the level of suPAR, which will aid in the stratification of patients in remission. Methodology: This observational pilot study included 48 subjects (24 rheumatoid arthritis [RA] patients in clinical remission as per the American College of Rheumatology criteria and 24 age-matched healthy individuals). 28-Joint Disease Activity Score (DAS28) calculator was used to calculate disease activity. Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and plasma suPAR levels were assessed using suPARnostic® ELISA Assay kit (ViroGates, Denmark). The inflammatory parameters such as CRP, ESR, and suPAR were recorded at the time the patients were defined to be in clinical remission. Results: The median of suPAR level among cases in remission was 4.94 ng/mL and in controls was 3.54 ng/mL. The level of serum suPAR among RA remission patients was significantly higher (P &lt; 0.001) than in healthy individuals (P &lt; 0.001). The median of DAS28 score was 2.10, ESR 23, and CRP was 2.66. Nonparametric analysis (Spearman’s rho test) showed a significant correlation (P = 0.008) between DAS28 and ESR. The receiver operating characteristic showed area under the curve of 0.954 with sensitivity 83.3%, specificity 100%, negative predictive value 84%, and positive predictive value 100%. Conclusion: High suPAR levels among patients with clinical remission of RA demonstrate that these patients do possess baseline inflammatory status and hence continued treatment is required despite normal to mild range of ESR, CRP, and/or DAS 28 score. Thus, suPAR is a prognostic biomarker that can aid in better therapeutic management to patients with RA remission.

Clinical manifestations and prognosis of giant cell arteritis: A retrospective cohort study

The aim of the study was to evaluate the clinical manifestations and survival of patients with giant cell arteritis (GCA).Methods. A retrospective study included 166 patients with newly diagnosed GCA. Clinical, laboratory and instrumental data, three sets of classification criteria were used to confirm the diagnosis: the American College of Rheumatology (ACR) 1990, the revised ACR criteria of 2016 and/or the new ACR and European Alliance of Associations for Rheumatology (EULAR) 2022 criteria. Some of the patients underwent instrumental investigations: temporal artery ultrasound Doppler (n=61), contrast-enhanced computed tomography (CT) (n=5), CT angiography (n=6), magnetic resonance imaging (n=4), magnetic resonance angiography (n=3) and 18F-FDG positron emission tomography/CT (n=47). Overall and recurrence-free survival were analyzed using survival tables, Kaplan – Meier method.Results. The most frequent first manifestations of GCA were headache (81.8%), weakness (64%), fever (63.8%) and symptoms of rheumatic polymyalgia (56.6%). Changes of temporal arteries in color duplex scanning were detected in 44 out of 61 patients. GCs therapy was performed in all patients who agreed to be treated (n=158), methotrexate was used in 49 out of 158 patients, leflunomide – in 9 patients. In 45 (28.5%) out of 158 patients a stable remission was achieved as a result of GCs monotherapy, in 120 (75.9%) patients long-term maintenance therapy with GCs was required to prevent exacerbations, including 71 (44.9%) patients – in combination with methotrexate or other immunosuppressive drugs. The follow-up period of patients with a history of relapses was 21.0 (8.0–54.0) months. Relapses developed in 73 (46.2%) patients. The overall one-year survival rate was 97.1% [95% confidence interval (CI): 94.3; 99.9], and the five-year survival rate of patients was 94.6% [95% CI: 90.2; 99.0]. The one-year relapse-free survival rate was 86.4% [95% CI: 80.5; 92.3], and the five-year relapse-free survival rate was 52.4% [95% CI: 42.0; 62.8]. 12 (7.2%) of 166 patients died. The cause of death was myocardial infarction in two patients, stroke in two patients, and breast cancer in one patient; in the remaining seven cases, the cause of death was not determined.Conclusion. Given the high frequency of disease exacerbation, patients with GCA require long-term follow-up, especially during the first year after diagnosis.

Knowledge on cause, clinical manifestation and treatment for fibromyalgia among medical doctors: A worldwide survey.

Hench introduced the fibromyalgia syndrome almost 50 years ago. In the meantime, the prevalence has increased, the clinical criteria have changed and the way we explain (chronic) pain has altered. In the current study, we conducted a worldwide survey in which we investigate whether medical doctors are familiar with the American College of Rheumatology (ACR) criteria for fibromyalgia and, if so, whether these medical doctors adhere to the clinical guidelines following evidence-based treatments. In total, 286 medical doctors from 43 countries spread over 6 continents filled out the survey. In most of the countries, the diagnosis fibromyalgia was used. Only 10% adhere to the ACR criteria, widespread pain (44%), unrefreshed sleep (24%), fatigue (20%) and cognitive problems (8%) were most used diagnostic criteria. Of the respondents, 94 (32%) mentioned that the cause is unknown or idiopathic, but also a wide variety of other causes was mentioned. More than 70 different treatment options were provided, of which 24% of the responses were classified as according to the clinical guidelines. From this study, we conclude that many medical doctors do not follow the ACR criteria; the majority has an inappropriate knowledge of causes for fibromyalgia and that a minority of treatment advice adhere to the guidelines.

Comparing tocilizumab biosimilar BAT1806/BIIB800 with reference tocilizumab in patients with moderate-to-severe rheumatoid arthritis with an inadequate response to methotrexate: a phase 3, randomised, multicentre, double-blind, active-controlled clinical trial

Biosimilars provide an opportunity to address unmet medical need by expanding access to biological treatments. This study aimed to show equivalent efficacy, and comparable safety, immunogenicity, and pharmacokinetic profiles of a proposed tocilizumab biosimilar BAT1806/BIIB800, to reference tocilizumab, in participants with rheumatoid arthritis with an inadequate response to methotrexate. This phase 3, multicentre, randomised, double-blind, active-controlled, equivalence study comprised a 24-week initial treatment period (results reported here) and a 24-week secondary treatment period. Participants were recruited at 54 centres across five countries (China, Ukraine, Poland, Georgia, and Bulgaria). Patients with active rheumatoid arthritis with an inadequate response to methotrexate were randomly assigned (1:1:2) to receive reference tocilizumab up to week 48, or reference tocilizumab up to week 24 followed by BAT1806/BIIB800 up to week 48 (the two reference tocilizumab groups were analysed as a single group in this analysis), or BAT1806/BIIB800 up to week 48 (the BAT1806/BIIB800 group), administered by intravenous infusion once every 4 weeks at a starting dose of 8 mg/kg. The primary endpoint was the proportion of participants who had a 20% improvement in American College of Rheumatology criteria (ACR20) at week 12 (for the European Medicines Agency [EMA]) or week 24 (for the US Food and Drug Administration [FDA] and China National Medical Products Administration [NMPA]) using prespecified equivalence margins (95% CI -14·5 to +14·5 [EMA], 90% CI -12·0 to +15·0 [FDA], and 95% CI -13·6 to +13·6 [NMPA]). The International Council for Harmonisation E9(R1) estimand framework, with strategies for addressing intercurrent events, was implemented for the efficacy evaluations with expected differences as per the predefined equivalence margins. This trial is registered at ClinicalTrials.gov (NCT03830203) and EudraCT (2018-002202-31), and is closed to new participants. Between Dec 19, 2018, and Jan 5, 2021, we randomly assigned 621 participants: 309 to the reference tocilizumab group and 312 to the BAT1806/BIIB800 group. The mean age was 50·5 years (SD 12·0), 534 (86%) were women, 87 (14%) were men, and 368 (59%) were White. For the primary estimands, estimated ACR20 response rates were 64·8% in the reference tocilizumab group and 69·0% in the BAT1806/BIIB800 group (treatment difference 4·1% [95% CI -3·6 to 11·9]) at week 12, and 67·9% in the reference tocilizumab group and 69·9% in the BAT1806/BIIB800 group (treatment difference 1·9% [90% CI -4·0 to 7·9; 95% CI -5·2 to 9·1]) at week 24. All confidence intervals were contained within the predefined equivalence margins. Comparable pharmacokinetic and immunogenicity profiles were observed for the reference tocilizumab and BAT1806/BIIB800 groups. Adverse events were reported by 201 (65%) participants in the reference tocilizumab group and 206 (66%) in the BAT1806/BIIB800 group; 196 (63%) participants in the reference tocilizumab group and 201 (64%) participants in the BAT1806/BIIB800 group reported a treatment-emergent adverse event. Five participants had a fatal event (reference tocilizumab n=1; BAT1806/BIIB800 n=4). BAT1806/BIIB800 showed equivalent efficacy, and comparable safety, immunogenicity, and pharmacokinetic profiles as reference tocilizumab. Bio-Thera Solutions and Biogen.

Decline in Incidence of Extra-Articular Manifestations of Rheumatoid Arthritis: A Population-Based Cohort Study.

The focus of this study was to assess changes in the cumulative incidence of extra-articular manifestations of rheumatoid arthritis (ExRAs) and associated mortality risk. This study evaluated trends in occurrence of ExRAs using a population-based inception cohort that included all adult patients with incident rheumatoid arthritis (RA) from 1985 through 2014 meeting the 1987 American College of Rheumatology criteria. Patients were divided into two cohorts based on the incidence date of RA, 1985 to 1999 and 2000 to 2014. The occurrence of ExRAs was determined by manual chart review, and the 10-year cumulative incidence was estimated for each ExRA in both cohorts. Cox proportional hazard models were used to determine associations between specific demographic and RA disease characteristics and ExRAs and between ExRAs and mortality. There were 907 patients included, 296 in the 1985 to 1999 cohort and 611 in the 2000 to 2014 cohort. The 10-year cumulative incidence of any ExRA decreased significantly between the earlier and later cohorts (45.1% vs 31.6%, P < 0.001). This was largely driven by significant declines in subcutaneous rheumatoid nodules (30.9% vs 15.8%, P < 0.001) and nonsevere ExRAs (41.4% vs 28.8%, P = 0.001). Identified risk factors for the development of any ExRAs include rheumatoid factor positivity (hazard ratio [HR] 2.02, 95% confidence interval [CI] 1.43-2.86) and current smoking (HR 1.61, 95% CI 1.10-2.34). Mortality was increased in patients with either nonsevere (HR 1.83, 95% CI 1.18-2.85) or severe ExRAs (HR 3.05, 95% CI 1.44-6.49). The incidence of ExRAs has decreased over time. Mortality remains increased in patients with ExRAs.