What do we measure with 28-joint DAS in elderly patients? An explorative analysis in the NOR-DMARD study.

OBJECTIVE: Insight into the influence of ageing on disease outcomes is limited. The objective of this study was to examine the potential effect of age on disease activity using the 28-joint DAS (DAS28) and its components in patients with RA. METHODS: Baseline data of DMARD-naïve patients with RA from the Norwegian Register of DMARDs were used. Linear regression explored the strength of the association between age (<45, 45-65 and >65 years) and each DAS28 component while accounting for education and gender. Adjusted predicted scores for DAS28 components and total DAS28 score were calculated for each age category. RESULTS: Baseline data from 2037 patients [mean age 55.2 years (s.d. 14.0), 68% females] were available. Regression models had to be stratified for gender (P for interaction <0.001); education was a significant covariate. Males >65 years of age with an intermediate level of education have a 56% higher ESR and 25% higher 28-joint swollen joint count as compared with their younger counterparts (<45 years). For females, corresponding differences were 51% and 27%, respectively. The age effect on the 28-joint tender joint count and patient global assessment was negligible. In patients with an intermediate education level, DAS28 was 5.0 vs 5.5 (10% increase) in the youngest vs oldest age groups, independent of gender. CONCLUSION: The age-related increase in ESR and 28-joint swollen joint count scores without a relevant corresponding increase in 28-joint tender joint count and patient global assessment might imply that age-related processes (e.g. soft tissue changes, physiological ESR increase) contribute to a higher DAS28 in elderly patients.

Role of the C-reactive Protein-to-Albumin Ratio in Assessing Disease Activity in Elderly Patients With Rheumatoid Arthritis.

OBJECTIVE: Nowadays, one measure that is more helpful in assessing the level of inflammation than either C-reactive protein (CRP) or albumin alone is the C-reactive protein-to-albumin ratio (CAR). Our study set out to assess the CAR in elderly individuals with rheumatoid arthritis (RA) and its correlation with other parameters. METHODS: Included in the research were patients who were being followed up on for RA between January 2021 and January 2024 and categorized according to their age at the time of enrolment and assigned to one of two groups: younger patients, defined as <60 years of age, and those aged ≥60 years, who were recorded as elderly patients. The clinical evaluation of the patients and laboratory data measured for each patient included age, gender, disease duration, medications, CRP, erythrocyte sedimentation rate (ESR), albumin, neutrophil-to-lymphocyte ratio (NLR), and CAR. Disease activity was assessed with the disease activity score 28 (DAS 28)-ESR. The health assessment questionnaire was used to measure the functional status. RESULTS: Ninety-four patients (<60 years: 58 and ≥60 years: 36) were included. The mean age of the elderly patients was 65.80 ± 5.33 years. Female predominance was similar in both the RA groups (<60 years: 50 patients (86.2%) vs. ≥60 years: 31 (86.1%)). The distribution of biological and disease-modifying drugs did not significantly differ between the groups. With the exception of albumin, there was no statistically significant difference between the groups for ESR, CRP, CAR, NLR, or DAS28-ESR. Elderly patients with a DAS28-ESR of 2.6 and above had a statistically significant higher CAR than the remission group (3.44±3.73 vs. 2.71±5.73, respectively). There was no statistically significant difference in the NLR value of elderly patients with a DAS28-ESR of 2.6 and above compared to the remission group (3.06 ± 2.95 vs. 2.65 ± 1.38, respectively). In addition, CAR was positively correlated with ESR, CRP, and DAS28-ESR (r = 0.726, p < 0.001; r = 0.954, p < 0.001; r = 0.339, p = 0.043, respectively). However, there was no discernible correlation between CAR and HAQ, NLR, or disease duration. CONCLUSION: In elderly RA patients, our study demonstrated the correlation between CAR and inflammatory biomarkers and the DAS28-ESR. According to this, CAR may prove to be a useful biomarker for assessing inflammation and disease activity in clinical settings.

The Cost-Effectiveness of and Adherence to Disease-Modifying Antirheumatic Drug (DMARD) Therapy in Rheumatoid Arthritis Patients in a Tertiary Care Teaching Hospital in Uttarakhand, India.

Objective This study was conducted with the aim of evaluating the cost-effectiveness of and adherence to treatment in patients on disease-modifying antirheumatic drug (DMARD) therapy for rheumatoid arthritis (RA) in a tertiary care teaching hospital in Uttarakhand, India. Methodology This prospective observational study was conducted on 150 rheumatoid arthritis patients presenting to the Rheumatology Outpatient Department (OPD) receiving DMARD therapy (approval number AIIMS/IEC/18/160). The patients were followed up for an average of 10.7 weeks and received drugs in four regimens with methotrexate (MTX) (Regimen 1) having the least contribution with a mean of 46.05 Rs, methotrexate + hydroxychloroquine (MTX + HCQ) (Regimen 2) with 174.15 Rs, methotrexate + hydroxychloroquine + leflunomide (MTX + HCQ + Lef) (Regimen 3) with Rs 371.70, and methotrexate + hydroxychloroquine + leflunomide + biological DMARD adalimumab (MTX + HCQ + Lef + bDMARD adalimumab) (Regimen 4) with 17,349.4 Rs. The cost of drug therapy was assessed by calculating the cost of therapy per month for each patient, and adherence was assessed using the Morisky-Green-Levine Scale (MGLS) at the follow-up visit. Results The overall mean cost of DMARD treatment was 205.81 Rs. The overall DMARD therapy cost-effectiveness was Rs 878.14 for a unit change of Disease Activity Score (DAS28). The most cost-effective treatment came out to be Regimen 1 with the least cost of 290.9 Rs for a unit change of DAS28, and the least cost-effective was Regimen 4 with 65,661.8 Rs for a unit change of DAS28. At follow-up, among all subjects of the study, 49 (32.7%) subjects showed high adherence, 71 (47.3%) subjects showed medium adherence, and 30 (20%) subjects showed low adherence. Accordingly, the maximum number of participants fell in the category of medium adherence, i.e., 71 (47.4%). Conclusion Our study concluded that the cost burden varied according to the number of DMARDs being given to the patient. The double-drug therapy of methotrexate + hydroxychloroquine had a maximum "high adherence." On a whole, the majority of patients had "medium adherence" to therapy.

Factors Leading to Diagnostic and Therapeutic Delay of Rheumatoid Arthritis and Their Impact on Disease Outcome.

Objective To identify the factors which lead to delay in diagnosis and initiation of disease-modifying anti-rheumatic drugs (DMARDs) in rheumatoid arthritis (RA) patients and their impact on disease outcome and functional ability. Methodology This cross-sectional study was conducted from June 2021 to May 2022 at the Department of Rheumatology and Immunology, Sheikh Zayed Hospital, Lahore. Inclusion criteria were patients aged >18 years who were diagnosed with RA, based on American College of Rheumatology (ACR) criteria 2010. Delay was defined as any sort of delay which leads to delay in diagnosis or initiation of treatment of more than three months. The factors and impact on disease outcome were measured by using Disease Activity Score-28 (DAS-28) for disease activity and Health Assessment Questionnaire-Disability Index (HAQ-DI) for functional disability. The collected data were analyzed with Statistical Package for Social Sciences (SPSS) version 24 (IBM Corp., Armonk, NY, USA). Results One hundred and twenty patients were included in the study. Mean delay in referral to a rheumatologist was 36.75±61.07 weeks. Fifty-eight (48.3%) patients with RA were misdiagnosed before presentation to a rheumatologist. Sixty-six (55%) patients had the perception that RA is a non-treatable disease. Delay in diagnosis of RA from onset of symptoms (lag 3) and delay in start of DMARDs from onset of symptoms (lag 4) were significantly associated with increased DAS-28 and HAQ-DI scores (p-value 0.001). Conclusion The factors which led to diagnostic and therapeutic delay were delayed consultation with a rheumatologist, old age, low education status and low socioeconomic status. Rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibodies had no role in diagnostic and therapeutic delay. Many RA patients were misdiagnosed with gouty arthritis and undifferentiated arthritis before consulting a rheumatologist. This diagnostic and therapeutic delay compromises RA management leading to high DAS-28 and HAQ-DI in RA patients.

Early and Late Response and Glucocorticoid-Sparing Effect of Belimumab in Patients with Systemic Lupus Erythematosus with Joint and Skin Manifestations: Results from the Belimumab in Real Life Setting Study-Joint and Skin (BeRLiSS-JS).

AIM: To assess the efficacy of belimumab in joint and skin manifestations in a nationwide cohort of patients with SLE. METHODS: All patients with skin and joint involvement enrolled in the BeRLiSS cohort were considered. Belimumab (intravenous, 10 mg/kg) effectiveness in joint and skin manifestations was assessed by DAS28 and CLASI, respectively. Attainment and predictors of DAS28 remission (<2.6) and LDA (≥2.6, ≤3.2), CLASI = 0, 1, and improvement in DAS28 and CLASI indices ≥20%, ≥50%, and ≥70% were evaluated at 6, 12, 24, and 36 months. RESULTS: DAS28 < 2.6 was achieved by 46%, 57%, and 71% of patients at 6, 12, and 24 months, respectively. CLASI = 0 was achieved by 36%, 48%, and 62% of patients at 6, 12, and 24 months, respectively. Belimumab showed a glucocorticoid-sparing effect, being glucocorticoid-free at 8.5%, 15.4%, 25.6%, and 31.6% of patients at 6, 12, 24, and 36 months, respectively. Patients achieving DAS-LDA and CLASI-50 at 6 months had a higher probability of remission at 12 months compared with those who did not (p = 0.034 and p = 0.028, respectively). CONCLUSIONS: Belimumab led to clinical improvement in a significant proportion of patients with joint or skin involvement in a real-life setting and was associated with a glucocorticoid-sparing effect. A significant proportion of patients with a partial response at 6 months achieved remission later on during follow-up.

CTHRC1: A New Candidate Biomarker for Improved Rheumatoid Arthritis Diagnosis.

Background: The purpose of this study was to determine whether plasma levels of the collagen triple helix repeat containing 1 (CTHRC1) protein can serve as a blood-based biomarker for improved diagnosis of rheumatoid arthritis (RA) patients and monitoring of RA disease activity. Methods: We measured levels of CTHRC1 in the plasma of patients diagnosed with RA, osteoarthritis (OA), reactive arthritis (ReA), as well as in healthy individuals. We then assessed the correlation between CTHRC1 protein and a range of indices including the 28-joint disease activity score (DAS28), rheumatoid factor (RF), C-reactive protein (CRP), anti-citrullinated protein antibodies (ACPA), erythrocyte sedimentation rate (ESR), as well as a panel of cytokines, including interleukin 1 beta (IL-1ß), interleukin 6 (IL-6), interleukin 8 (IL-8), and interferon gamma (IFNγ). Receiver operating characteristic (ROC) analysis was further performed to assess the diagnostic value of CTHRC1. Results: CTHRC1 plasma levels were significantly elevated in RA patients compared to healthy individuals, OA and ReA patients. ROC curve and risk score analysis suggested that plasma CTHRC1 can accurately discriminate patients with RA from healthy controls and may have practical value for RA diagnosis. CTHRC1 levels were positively associated with RF, ACPA, CRP, and disease activity based on the combined index of DAS28 with CRP (DAS28-CRP), and also strongly correlated with IL-1ß, IL-6, IL-8, and IFNγ. Conclusion: Our studies show that CTHRC1 is a sensitive and easy-to-measure plasma marker that differentiates between RA and healthy status and also distinguishes between RA and other forms of arthritis, such as OA and ReA. At the current level of understanding, plasma CTHRC1 levels may improve the diagnosis of RA and these findings warrant confirmation in a larger, more comprehensive patient population.

Antibodies against citrullinated peptides are associated with clinical and radiological outcomes in patients with early rheumatoid arthritis: a prospective longitudinal inception cohort study.

Introduction: Anticitrullinated peptide antibody (ACPA) responses for 22 citrullinated peptides in patients with early rheumatoid arthritis (RA) were analysed and related to radiological and clinical outcome during the first 2 years in a prospective inception cohort. Methods: The ACPA reactivities were assessed in 1022 patients with early RA (symptoms <12 months) using the custom-made microarray chip (Thermo Fisher Scientific, Uppsala, Sweden) in a prospective longitudinal study of observational assessments of Disease Activity Score (DAS28 and its components) and radiology during the first 24 months, accounting for the treatment. Results: Frequency of ACPA reactivities varied between 13.3% and 63.1%. Of the anticyclic citrullinated peptide-2 (anti-CCP2) antibody-negative patients, ACPA reactivities were positive in 32.6%. Smoking, human leucocyte antigen-shared epitope (HLA-SE), anti-CCP2/rheumatoid factor, protein tyrosine phosphatase non-receptor type 22 (1858C/T) and DAS28 were significantly associated with number of ACPA reactivities. The ACPA reactivities modified differently the development of DAS28 over 24 months (identified using trajectories). Anti-Filaggrin307-324, anti-hnRNP (Peptide)-Z1 and anti-F4-CIT-R antibodies anticipated lower DAS28 values (p<0.01-0.05), while positivity for anti-Fibrinogen(Fib)ß62-78(74), and anti-Fibα563-583 predicted higher DAS28 (p<0.01 both). Interaction between anti-Fibß36-52, anti-Pept-5 and anti-Bla-26 antibodies, respectively, and DAS28 during 24 months decreased significantly the DAS28 values (p<0.01-0.05). Corticosteroids and biologicals were related to DAS28-area under the curve and Larsen score 24 months. Anti-vimentin2-17 antibodies remained significantly associated with Larsen score at baseline and 24 months, respectively, and radiological progression, besides biologicals at 24 months adjusted for sex and age. Conclusions: Several ACPA reactivities modified significantly the DAS28 development during the first 24 months and were significantly associated with Larsen score at baseline, 24 months and radiological progression.

[Acupuncture combined with western medicine on rheumatoid arthritis and effects on blood stasis].

OBJECTIVE: To observe the clinical efficacy of acupuncture combined with western medicine in the treatment of rheumatoid arthritis (RA) and its effect on blood stasis, and to explore ways to improve the clinical curative effect. METHODS: A total of 56 patients of RA were randomly divided into an observation group and a control group, 28 cases in each one. ① ibuprofen sustained-release tablets, 2 times a day, each time 0.3 g; ② methotrexate tablets (MTX), once a week, each time 10 mg ③ folic acid tablets, once a week, each time 5 mg were given in the control group, 30 days as one course, a total of 3 courses were required. In the observation group, acupuncture was adopted on the basis of the treatment as the control group. The main acupoints were Ganshu (BL 18), Pishu (BL 20), Shenshu (BL 23), Hegu (LI 4), Quchi (LI 11), Zusanli (ST 36) combined with local ashi points. The treatment was given once every day for continuous 6 days a week, the treatment for 30 days as one course, a total of 3 courses were required. The serological indexs were evaluated before and after treatment, including the rheumatoid factor (RF), hypersensitive C-reactive protein (hs-CRP), erythrocyte sedirnentation rate (ESR), platelet (PLT), fibrinogen (FBG) and D-dimer (D-D), the changes of disease activity score (DAS-28), symptom grade quantitative score, blood stasis syndrome symptom (the joint tingling, lip color, tongue, pulse, subcutaneous ecchymosis, squamous and dry skin) score were observed. RESULTS: ① The scores of RF, hs-CRP, ESR, PLT, D-D, FBG, DAS-28 and symptom grade quantitative were significantly improved in the two groups compared with those before treatment (all P<0.05), and the scores of hs-CRP, ESR, DAS-28 and symptom grading in the observation group were more better than those in the control group (all P<0.05). ② The total score of joint tingling, lip color, tongue, pulse, subcutaneous ecchymosis, squamous and dry skin and blood stasis syndrome in both groups were decreased after treatment (all P<0.05), the joint tingling, tongue, lip color and subcutaneous ecchymosis were improved obviously in the observation group than those in the control group (all P<0.05). ③ The total effective rate in the observation group was 85.7% (24/28), which was better than 75.0% (21/28) in the control group (P<0.05). CONCLUSION: Acupuncture combined with western medicine can not only improve the clinical efficacy of RA patients but also improve the blood stasis.

Effectiveness of arthroscopic elbow synovectomy in rheumatoid arthritis patients: Long-term follow-up of clinical and functional outcomes.

OBJECTIVE: To determine the long-term clinical and functional results of arthroscopic elbow synovectomy in rheumatoid arthritis patients with refractory elbow synovitis in terms of improvement in pain, function, and active range of motion (AROM) or arc of motion. METHOD: Fifteen rheumatoid elbows in 13 patients, not responding to DMARD therapy and with radiological changes not more than Larsen grade 3 were taken, who underwent arthroscopic elbow synovectomy. The main outcome measured in forms of Mayo Elbow Performance Scale (MEPS) score, measurement of pain using a Visual Analogue Scale (VAS), radiological angles of elbow, disease activity score (DAS-28), arc of motions (AOM) and complications, which were assessed at follow-up periods of 6 months, 24 months, and 30 months. Statistical analysis was done both qualitatively and quantitatively. Mann-Whitney U test, chi-square test, and Student t test were used as the statistical test for determining significance. RESULTS: In the study group, the improvement was sustained and significant as compared to baseline (VAS 1.28, MEPS 81.07 and mean flexion range 85°) (p value <0.001). No significant complications were encountered postoperatively after elbow synovectomy. CONCLUSION: The study assesses the long-term results of arthroscopic synovectomy in elbow synovitis secondary to rheumatoid arthritis with significant results favoring arthroscopic synovectomy.