28-joint Disease Activity Score Research Articles

The effect of a tight control regime with monthly follow-up on remission rates and reported pain in early rheumatoid arthritis.

To determine whether a tight control (TC) regime with monthly consultations to the physician for the first 6months, could increase remission rate and improve reported pain of patients with early rheumatoid arthritis (RA). In this single-centre, TC study, with monthly visits to the physician, a cohort of 100 patients with early RA was consecutively included. They were compared with a reference cohort of 100 patients from the same clinic that had been conventionally managed. The patients were followed for 2years. The patients in the TC cohort had lower 28- joints disease activity score (DAS28) at three, six, 12 and 24months, compared with the conventionally managed cohort, p≤0.001. At 12months, 71% in the TC cohort versus 46% in the conventional cohort were in remission (DAS28<2.6) and at 24months 68% versus 49% respectively, p<0.05. The TC cohort reported less pain at three, six, 12 and 24months, p<0.001. Multiple logistical regression analyses adjusted for, respectively, age, disease duration, pharmacological treatment, DAS28 and visual analogue scale pain at inclusion, revealed that participation in the TC cohort had an independent positive association with remission at 12 and 24months and with acceptable pain at 24months. The intensive follow-up schedule for patients with early RA improved remission and led to improvement in reported pain and physical function. The positive effect of a TC regime in early disease may be due to increased empowerment, developed by meeting health professionals frequently.

Long-Term Efficacy and Safety of Risankizumab in Patients with Active Psoriatic Arthritis: Results from a 76-Week Phase 2 Randomized Trial.

IntroductionThe objective of this work was to assess the efficacy and safety of risankizumab in psoriatic arthritis (PsA) over 76 weeks.MethodsIn this double-blind, dose-ranging phase 2 study, adults with active PsA were randomized 2:2:2:1:2 to risankizumab 150 mg at weeks 0, 4, 8, 12, and 16 (arm 1), 150 mg at weeks 0, 4, and 16 (arm 2), 150 mg at weeks 0 and 12 (arm 3), 75 mg at week 0 (arm 4), or placebo (arm 5). Patients completing week 24 could receive risankizumab 150 mg in a 52-week open-label extension study. Efficacy assessments included American College of Rheumatology (ACR) responses, Psoriasis Area Severity Index (PASI) responses, minimal disease activity (MDA), and 28-joint Disease Activity Score based on C-reactive protein (DAS28[CRP]).ResultsOf 185 randomized patients, 173 (93.5%) completed week 16 and 145 (78.4%) entered the open-label extension. Significantly more patients in each risankizumab arm achieved ACR20 at week 16 versus placebo (primary endpoint: pooled arms 1 + 2 [59.5%] versus placebo [35.7%]; treatment difference [90% CI] 24.0 [9.3, 38.7]; P = 0.007). Similarly, significantly more patients in most risankizumab arms achieved ACR20/50/70, PASI75/90/100, MDA, and greater improvements in DAS28(CRP) versus placebo at week 16. These benefits of risankizumab were maintained long term. Treatment-emergent adverse events were comparable across treatment arms. Risankizumab 150 mg was well tolerated over 76 weeks.ConclusionsRisankizumab improved joint and skin symptoms versus placebo in patients with active PsA over 16 weeks; improvements were sustained long term. Risankizumab was well tolerated over the long term with no new safety findings.Trial Registration NumbersNCT02719171 and NCT02986373.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40744-022-00474-5.

Effects of anti-SSA antibodies on the response to methotrexate in rheumatoid arthritis: A retrospective multicenter observational study.

Comparison of clinical response to methotrexate between anti-SSA antibody-positive and -negative patients with methotrexate-naïve rheumatoid arthritis and investigate the reasons for the differences in the response. For this multicenter retrospective cohort study, a total of 210 consecutive patients with rheumatoid arthritis who newly initiated methotrexate were recruited. The effects of anti-SSA antibody positivity on achieving a low disease activity according to the 28-joint Disease Activity Score based on C-reactive protein after 6 months of methotrexate administration were investigated using a logistic regression analysis. This study involved 32 and 178 anti-SSA antibody-positive and -negative patients, respectively. The rate of achieving low disease activity according to the 28-joint Disease Activity Score based on C-reactive protein at 6 months was significantly lower in the anti-SSA antibody-positive group than in the anti-SSA antibody-negative group (56.2% vs. 75.8%, P = 0.030). After 6 months, anti-SSA antibody-positive patients had significantly higher scores on the visual analogue scale (median [interquartile range]: 22 [15-41] vs. 19 [5-30], P = 0.038) and were frequently prescribed nonsteroidal anti-inflammatory drugs (37.5% vs. 18.0%, P = 0.018). In conclusion, the presence of anti-SSA antibodies might be a predictive factor for insufficient responses to treat-to-target strategy in rheumatoid arthritis. Residual pain might contribute to the reduced clinical response to methotrexate in anti-SSA antibody-positive patients with rheumatoid arthritis.

TNF-α Inhibitors in Combination with MTX Reduce Circulating Levels of Heparan Sulfate/Heparin and Endothelial Dysfunction Biomarkers (sVCAM-1, MCP-1, MMP-9 and ADMA) in Women with Rheumatoid Arthritis.

Sulfated glycosaminoglycans (sGAGs) are likely to play an important role in the development and progression of rheumatoid arthritis (RA)-associated atherosclerosis. The present study investigated the effect of anti-tumor necrosis factor-α (anti-TNF-α) therapy in combination with methotrexate on plasma sGAG levels and serum markers of endothelial dysfunction. Among sGAG types, plasma chondroitin/dermatan sulfate (CS/DS) and heparan sulfate/heparin (HS/H) were characterized using electrophoretic fractionation. Serum levels of soluble vascular cell adhesion molecule-1 (sVCAM-1), monocyte chemoattractant protein-1 (MCP-1), matrix metalloproteinase-9 (MMP-9) and asymmetric dimethylarginine (ADMA) were measured by immunoassays. The measurements were carried out four times: at baseline and after 3, 9 and 15 months of anti-TNF-α therapy. All analyzed parameters, excluding ADMA, were significantly elevated in patients with RA before the implementation of biological therapy compared to healthy subjects. Performed anti-TNF-α treatment led to a successive decrease in HS/H levels toward normal values, without any effect on CS/DS levels in female RA patients. The treatment was also effective at lowering the serum levels of sVCAM-1, MCP-1, MMP-9 and ADMA. Moreover, a significant positive correlation was found between the circulating HS/H and the 28 joint disease activity score based on the erythrocyte sedimentation rate (DAS28-ESR, r = 0.408; p <0.05), MCP-1 (r = 0.398; p <0.05) and ADMA (r = 0.396; p <0.05) in patients before the first dose of TNF-α inhibitor. In conclusion, a beneficial effect of anti-TNF-α therapy on cell-surface heparan sulfate proteoglycans (HSPGs)/HS turnover and endothelial dysfunction was observed in this study. This was manifested by a decrease in blood HS/H levels and markers of endothelial activation, respectively. Moreover, the decrease in the concentration of HS/H in the blood of patients during treatment, progressing with the decline in disease activity, indicates that the plasma HS/H profile may be useful for monitoring the efficacy of anti-TNF-α treatment in patients with RA.

Serum 14-3-3η as predictor of clinical remission and progression of structural damage in early rheumatoid arthritis following a treat-to-target strategy in a randomized controlled trial

Objective 14-3-3η is a proinflammatory mediator critical to joint destruction in rheumatoid arthritis (RA). We aimed to evaluate serum 14-3-3η for predicting disease activity and radiographic progression in patients with early RA in the double-blinded, randomized OPERA trial. Method 180 patients with early RA were randomized to receive methotrexate (MTX) + adalimumab or MTX + placebo in combination with glucocorticoid injections into swollen joints. Disease activity was measured using the 28-joint Disease Activity Score–C-reactive protein (DAS28-CRP). Clinical remission was defined as DAS28-CRP < 2.6. X-rays of hands and feet were evaluated by the Total Sharp van der Heijde score (TSS). Radiographic progression was defined as exceeding the smallest detectable change (1.8 TSS-units). Serum 14-3-3η was determined by enzyme-linked immunosorbent assay. Multivariate logistic regression models were used to identify predictors of DAS28-CRP remission at 6 months and radiographic progression at 12 months. Results Baseline 14-3-3η was a borderline significant independent predictor of radiographic progression at 12 months (odds radio = 1.02, 95% confidence interval 1.00–1.03, p = 0.05). In anti-cyclic citrullinated peptide antibody (ACPA)-negative patients, a moderate/high baseline 14-3-3η concentration increased the risk of radiographic progression at 12 months [4/51 (8%) vs 3/9 (33%), χ2 = 4.823, p = 0.028]. No value of 14-3-3η for predicting achievement of clinical remission was found. Conclusion Serum 14-3-3η was a borderline significant predictor of radiographic progression, particularly in ACPA-negative patients, but not of predicting achievement of clinical remission. Optimal cut-off levels of 14-3-3η for predicting radiographic progression in RA need further clarification.

Safety and effectiveness of certolizumab pegol in Japanese patients with rheumatoid arthritis: Results from a 24-week post-marketing surveillance study.

To report 24-week safety and effectiveness of certolizumab pegol (CZP) in Japanese patients with rheumatoid arthritis from a post-marketing surveillance study. Enrolled patients were newly receiving CZP. All adverse events (AEs) and adverse drug reactions (ADRs) were recorded for patients who received ≥1 CZP dose. Effectiveness outcomes included: 28-joint Disease Activity Score with erythrocyte sedimentation rate (DAS28-ESR) and European Alliance of Associations for Rheumatology (EULAR) response. Missing data were imputed using the last observation carried forward. 3727 patients were enrolled; safety and effectiveness were evaluated in 3586 and 1794 patients, respectively. 24.9% of patients reported AEs (893/3586), 14.7% reported ADRs (528/3586), 8.3% (298/3586) reported serious AEs and 5.3% (190/3586) reported serious ADRs. Selected serious ADRs of interest: infections (110; 3.1%), tuberculosis (6; 0.2%), interstitial pneumonia (15; 0.4%), malignancy (8; 0.2%), and hepatic function disorder (7; 0.2%). No allergic reactions, autoimmune disease, cardiac failure, demyelinating diseases, or pancytopenia were reported. Mean DAS28-ESR reduced from 4.8 (baseline) to 3.4 (final evaluation). At final evaluation, 34.7% of patients achieved EULAR good response. These real-world safety and effectiveness results were consistent with previously reported data, with no new safety signals identified. Long-term, real-world CZP safety and effectiveness data are needed.

Safety and Effectiveness of Abatacept in a Prospective Cohort of Patients with Rheumatoid Arthritis–Associated Interstitial Lung Disease

Objective: To prospectively evaluate the safety and efficacy profile of abatacept in patients with rheumatoid arthritis–associated interstitial lung disease (RA-ILD). Methods: We performed a prospective observational multicenter study of a cohort of patients with RA-ILD treated with abatacept between 2015 and 2021. Patients were evaluated using high-resolution computed tomography and pulmonary function tests at initiation, 12 months, and the end of follow-up. The effectiveness of abatacept was evaluated based on whether ILD improved, stabilized, progressed, or was fatal. We also evaluated factors such as infection, hospitalization, and inflammatory activity using the 28-joint Disease Activity Score with the erythrocyte sedimentation rate (DAS28-ESR). Cox regression analysis was performed to identify factors associated with progression of lung disease. Results: The study population comprised 57 patients with RA-ILD treated with abatacept for a median (IQR) of 27.3 (12.2–42.8) months. Lung disease had progressed before starting abatacept in 45.6% of patients. At the end of follow-up, lung disease had improved or stabilized in 41 patients (71.9%) and worsened in 13 (22.8%); 3 patients (5.3%) died. No significant decreases were observed in forced vital capacity (FVC) or in the diffusing capacity of the lung for carbon monoxide (DLCO).The factors associated with progression of RA-ILD were baseline DAS28-ESR (OR [95% CI], 2.52 [1.03–3.12]; p = 0.041), FVC (OR [95% CI], 0.82 [0.70–0.96]; p = 0.019), and DLCO (OR [95% CI], 0.83 [0.72–0.96]; p = 0.018). Only 10.5% of patients experienced severe adverse effects. Conclusion: Pulmonary function and joint inflammation stabilized in 71% of patients with RA-ILD treated with abatacept. Abatacept had a favorable safety profile.

Iguratimod versus salazosulfapyridine in rheumatoid arthritis patients with an inadequate response to methotrexate: Adjusted with propensity score matching.

Methotrexate (MTX) is recommended as a first-line conventional synthetic disease-modifying antirheumatic drug (csDMARD) for treating rheumatoid arthritis (RA). This retrospective study sought to identify an add-on csDMARD treatment strategy for RA patients with MTX-inadequate response (IR). We collected the cases of RA patients treated with salazosulfapyridine (SASP) or iguratimod (IGU) as the additional csDMARD for MTX-IR during a 24-month follow-up. We performed propensity score matching to evaluate the retention rate, clinical efficacy, and safety profile (n = 54, each group). The retention rates at 24 months were 38.5% (MTX+SASP group) and 67.8% (MTX+IGU group). At 3 and 6 months, the MTX+IGU group's 28 joint-disease activity score (DAS28) was significantly decreased versus the MTX+SASP group, and at 3 months the MTX+IGU group's good-responder percentage (22.9%) was significantly higher versus the MTX+SASP group's good-responder percentage (10.7%). Conversely, compared to the MTX+SASP group, the MTX+IGU group showed a greater reduction in the estimated glomerular filtration rate from baseline during follow-up. IGU is a useful add-on csDMARD for RA patients with MTX-IR; its high retention rate and good clinical response make it a useful combination therapy for controlling RA disease activity. However, the renal function should be monitored during follow-up.

Association between TNFi anti-drug antibodies, smoking, and disease activity in patients with inflammatory arthritis: Results from a Norwegian cross-sectional observational study.

IntroductionWe aimed to compare demographics and clinical characteristics between patients with inflammatory arthritis (IA) with vs. without neutralizing anti-drug antibodies (nADAb) against tumor necrosis factor inhibitors (TNFi). A secondary aim of the study was to explore if current smokers were more frequently nADAb-positive.MethodsTNFi-treated outpatients with IA were recruited and a broad range of disease activity measures were assessed. nADAb were assessed using a reporter gene assay. Comparisons between nADAb-positive and -negative patients were done in unadjusted analyses as well as in adjusted logistic regression and general linear models.ResultsA total of 282 patients with IA currently under treatment with TNFi were included. nADAb were identified in 11 patients (nine treated with infliximab, one with etanercept and one with certolizumab pegol). Patients with nADAb reported significantly worse joint pain, patient’s global assessment, Health Assessment Questionnaire, Bath Ankylosing Spondylitis Disease Activity/Functional Index and Short-Form-36 physical functioning scale score than patients without nADAb (p < 0.04, adjusted analyses). 28-joint Disease Activity Score, Simplified Disease Activity Index and Maastricht Ankylosing Spondylitis Enthesitis score were also significantly worse in the nADAb-positive patients (p < 0.04, adjusted analyses), as were serum calprotectin, C-reactive protein and numbers of circulating peripheral leukocytes (p ≤ 0.001). A significantly higher proportion of nADAb-positive patients were current smokers (46 vs. 15%), in unadjusted as well as adjusted analyses (p ≤ 0.008).ConclusionsnADAb-positive patients were more frequently smokers and had significantly worse disease activity, physical function, and inflammatory markers, than patients without nADAb. The association between smoking and nADAb positivity warrants further examination.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40744-022-00464-7.

Association of serum hepatoma-derived growth factor levels with disease activity in rheumatoid arthritis: A pilot study.

BackgroundHepatoma‐derived growth factor (HDGF) is reported to play an important role in tumorigenesis and cancer progression. However, growing evidence indicates its participation in immune system activation. This study analyzed the relationship among serum HDGF levels, disease activity, and laboratory markers in patients with rheumatoid arthritis (RA).MethodsBlood samples from 165 patients with RA, 42 with osteoarthritis (OA), and 28 healthy controls, were used to evaluate the serum HDGF levels. Correlations of serum HDGF levels with age, 28‐joint count disease activity score (DAS28), and laboratory findings were assessed by Pearson correlation and receiver operator characteristic (ROC) curve analyses to obtain HDGF optimal cutoffs according to the disease status. Immunohistochemical staining was performed on the knee synovial tissue samples from patients with RA and OA (n = 10 each) to investigate HDGF joint expression.ResultsSerum HDGF levels were significantly correlated with DAS28 erythrocyte sedimentation rate (r = 0.412, p < 0.001) and C‐reactive protein values (r = 0.376, p < 0.001). The optimal cutoffs of serum HDGF levels from the ROC analysis were 5.79 and 5.14 for the differentiation of active/inactive disease and remission/non‐remission, respectively. The ideal cutoff of serum HDGF levels to differentiate RA and OA was determined as 5.47. Serial serum HDGF level analyses in 21 patients with RA revealed that serum HDGF levels significantly decreased after improvement in disease activity (p = 0.046). HDGF expression was not observed in the synovial tissues of the patients with RA and OA.ConclusionSerum HDGF level could be a potential laboratory biomarker for the severity of RA.

Comparison of treatment of severe rheumatoid arthritis patients with biological agents and JAK-STAT inhibitors. An observational study.

IntroductionTreatment of severe rheumatoid arthritis (RA) is currently based either on biological agents or Janus kinase/signal transducer and activator of transcription inhibitors, most often in combination with methotrexate (MTX).Aim of the studyThe aim of the study was to compare the effectiveness and side effects of bio- logic disease-modifying antirheumatic drugs (bDMARDs) and targeted synthetic (ts) DMARDs treatment.Material and methodsThe analysis included 108 RA patients with active disease treated with MTX 25 mg per week. Eighty patients (group I) were treated with bDMARDs and 28 patients (group II) with JAK-STAT inhibitors. The duration of morning stiffness, pain on Visual Analogue Scale (VAS), 28-joints Disease Activity Score (DAS28) and Simplified Disease Activity Score (SDAI) were assessed. Classical radiographic images of patients’ hands and feet using the Larsen and Dale’s criteria were evaluated. The effects of treatment with bDMARDs and tsDMARDs were analyzed.ResultsAll studied patients presented at least Larsen and Dale’s stage 3 of X-ray changes typical for RA. There were no statistically significant differences in disease duration, ESR, CRP, DAS28 and SDAI values between studied groups. Patients from group II previously used higher numbers of bDMARDs than group I treated with bDMARDs. Low disease activity after treatment was achieved by all patients; therefore patients from group II (treated with tsDMARDs) achieved lower values of patients’ global assessment on VAS.ConclusionsThe results of the present observational study indicated that treatment with JAK inhibitors is very promising. These drugs are not inferior in effectiveness to bDMARDs. It is important to monitor patients for thromboembolic events before and during JAK treatment.

Cost-effectiveness analyses of biologic and targeted synthetic disease-modifying anti-rheumatic diseases in patients with rheumatoid arthritis: Three approaches with a cohort simulation and real-world data.

To assess the cost-effectiveness of biologic and targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARDs) in rheumatoid arthritis. We conducted three analyses: a lifetime analysis with a cohort model (Study A) and two short-term analyses (Studies B and C). Study A evaluated the incremental cost-effectiveness ratio (ICER) per quality-adjusted life-year (QALY) gained from costs of standard treatments. Study B evaluated yearly costs per person achieving American College of Rheumatology (ACR) response (ACR20, ACR50, and ACR70), and Study C evaluated costs per person achieving previously defined claims-based effectiveness (equivalent to 28-joint Disease Activity Score ≤ 3.2). The proportion of ACR responders to the drugs of interest were determined by mixed treatment comparisons. Studies B and C estimated costs using a claims database. In Study A, ICERs of all b/tsDMARDs were lower than 5.0 million Japanese yen (JPY) per QALY. In Study B, yearly costs per person with ACR50 response were lower for subcutaneous tocilizumab (TCZ-SC; 1.9 million JPY) and SC abatacept (2.3 million JPY). In Study C, costs per person were lower for TCZ-SC (1.3 million JPY) and intravenous TCZ (1.6 million JPY) and effectiveness rates were higher for intravenous TCZ (45.3%) and infliximab (43.0%). The b/tsDMARDs with lower prices showed higher cost-effectiveness.

Clinical characteristics and variants that predict prognosis of difficult-to-treat rheumatoid arthritis.

Factors influencing prognosis after administration of the last biologic or targeted synthetic disease-modifying antirheumatic drug (b/tsDMARD) to patients with difficult-to-treat rheumatoid arthritis (D2T_RA) were evaluated in a clinical setting. RA patients who met the EULAR definition of D2T_RA were recruited. These patients were grouped according to success/failure. Success was defined as sustained within light disease activity or discontinued after clinical remission, and all of the following were met, including glucocorticoid (GCS) < 7.5mg/day, no rapid radiographic progression, and improved quality of life from the beginning of the b/tsDMARD (baseline). Failure was defined as any other condition from success. The primary endpoint of the study was success or failure at 12months after baseline. Factors influencing success/failure were statistically evaluated. A total of 71 D2T_RA patients were selected, 22 were in the success group and 49 in the failure group. For patients taking GCS and methotrexate (MTX) ≤ 8.6mg/week, only one was included in the success group and the other 24 were included in the failure group (p < 0.001). Of the 18 patients without GCS and with MTX ≥ 8.7mg, 12 patients whose 28-joint disease activity score ≤ 1.90 at 3months or ≤ 2.54 at 6months were in the success group (p < 0.01). D2T_RA patients with GCS or MTX ≤ 8.6mg at baseline are considered to be at high risk of repeat D2T_RA. Patients with no GCS and MTX ≥ 8.7mg are more likely to withdraw from D2T_RA if their disease activity is tightly controlled.

Efficacy of Tocilizumab Monotherapy Versus Tocilizumab and Methotrexate Combination Therapy in the Prevention of Radiographic Progression in Rheumatoid Arthritis: An Analysis Using Individual Patient Data From Multiple Clinical Trials

ObjectiveTo compare the effects of preventing radiographic progression (in its 3 components) of tocilizumab (TCZ) monotherapy with those of TCZ and methotrexate (MTX) in combination therapy (TCZ + MTX), and to evaluate possible effect modifiers in this model.MethodsRandomized trials that compared TCZ monotherapy to TCZ + MTX combination therapy for differences in radiographic progression were analyzed on an individual patient data level using mixed‐effects models, and data were collected from 820 subjects with either early rheumatoid arthritis (RA) or established RA. Outcomes were classified as the absence of radiographic progression after 2 years (i.e., preventing radiographic progression) as measured by total Sharp/van der Heijde score (SHS), erosion score, and joint space narrowing (JSN) score. Effect modification by baseline joint damage, disease duration, and Disease Activity Score in 28 joints (DAS28) was studied.ResultsOverall, TCZ + MTX combination therapy was more effective in preventing radiographic progression compared to TCZ monotherapy, which was measured by total SHS score. However, in patients with early RA who had more joint damage compared to those with less joint damage at baseline (relative risk [RR] 1.02 versus RR 0.91, respectively) or in patients with a lower DAS28 score compared to those with a higher DAS28 score (RR 1.04 versus RR 0.92, respectively) at baseline, this advantage disappeared. In patients with established RA, the advantage of TCZ + MTX versus TCZ alone in the prevention of radiographic progression disappeared with a longer disease duration at baseline (RR 1.04 versus 0.83). Results of erosion scores as an outcome were in line with these findings, though findings for JSN scores were less clear.ConclusionCombination therapy with TCZ + MTX is more effective in preventing radiographic progression compared to TCZ monotherapy, but the effectiveness of TCZ monotherapy may approximate the effectiveness of TCZ + MTX in patients with early RA who have more joint damage and/or a lower DAS28 at baseline and in patients with established RA who have longer disease duration.

Evaluation of fracture risk in Egyptian rheumatoid arthritis patients by the Fracture Risk Assessment Tool

BackgroundRheumatoid arthritis (RA) patients have a risk of fractures due to secondary osteoporosis. This study aimed to evaluate the probability of fractures in the next 10 years in Egyptian RA patients by the Fracture Risk Assessment Tool (FRAX).ResultsThe study was a case–control study. It included a hundred RA patients as well as 51 apparently healthy volunteers. Bone mineral density (BMD) means of lumbar vertebra, femoral neck, and total femur were significantly lower in the RA patient group. Additionally, FRAX of the major osteoporotic and hip fractures means were significantly higher in the RA group than in the control group. It was also found that age, body mass index (BMI), Health Assessment Questionnaire Disability Index (HAQ-DI), and BMD of the femoral neck were significant predictors of FRAX of major osteoporotic and hip fractures (P ≤ 0.05). The cumulative dose of steroids was a significant predictor for FRAX of major osteoporotic fractures; however, the 28 joints disease activity score calculated with erythrocyte sedimentation rate (ESR) (DAS28-ESR) was a significant predictor for FRAX of hip fractures.ConclusionsRA patients have a high fracture risk probability. Regular annual screening for BMD and FRAX of major osteoporotic and hip fractures is necessary for those patients.

Relative remission rates of Janus kinase inhibitors in comparison with adalimumab in patients with active rheumatoid arthritis: anetwork meta-analysis.

The relative remission rates of tofacitinib, baricitinib, upadacitinib, and filgotinib compared with those of adalimumab were assessed in patients with rheumatoid arthritis (RA) who responded poorly to methotrexate (MTX). We performed aBayesian network meta-analysis to combine direct and indirect evidence from randomized controlled trials (RCTs) to examine the Disease Activity Score in 28joints with C‑reactive protein (DAS28-CRP), the Clinical Disease Activity Index (CDAI), the Simplified Disease Activity Index (SDAI), and the Boolean remission of tofacitinib, baricitinib, upadacitinib, filgotinib, and adalimumab in RA patients with inadequate responses to MTX. Four RCTs, comprising 3507patients, met the inclusion criteria. The filgotinib 200 mg + MTX and upadacitinib 15 mg + MTX groups showed asignificantly higher DAS28-CRP < 2.6 than adalimumab 40 mg + MTX. Upadacitinib 15 mg + MTX showed asignificantly higher CDAI (≤ 2.8) than adalimumab 40 mg + MTX (odds ratio [OR]: 1.62; 95% credible interval [CrI]: 1.16-2.29). The ranking probability based on the surface under the cumulative ranking curve (SUCRA) indicated that upadacitinib 15 mg + MTX had the highest probability of being the best treatment as it achieved aCDAI ≤ 2.8, followed by filgotinib 200 mg + MTX, baricitinib 4 mg + MTX, tofacitinib 5 mg + MTX, and adalimumab 40 mg + MTX. The Boolean remission showed the same distribution pattern as that of the CDAI ≤ 2.8. Upadacitinib 15 mg + MTX showed asignificantly higher SDAI ≤ 3.3 than adalimumab 40 mg + MTX (OR: 1.62; 95% CrI: 1.16-2.28). SUCRA ranking based on SDAI ≤ 3.3 indicated that upadacitinib 15 mg + MTX had the highest probability of being the best treatment for achieving an SDAI ≤ 3.3, followed by baricitinib 4 mg + MTX, filgotinib 200 mg + MTX, tofacitinib 5 mg + MTX, and adalimumab 40 mg + MTX. In RA patients with an inadequate response to MTX, remission rates with JAK inhibitors were significantly higher; there is evidence fordifferences in efficacy regarding remission among the different JAK inhibitors.

Does tenosynovitis of the hand detected by B-mode ultrasound predict loss of clinical remission in rheumatoid arthritis? Results from a real-life cohort.

ObjectiveThe role of US-detected tenosynovitis (USTS) in the management of rheumatoid arthritis remains controversial. The aim of this study was to investigate whether tenosynovitis can predict a flare in rheumatoid arthritis patients in remission in a real-life cohort.MethodsRheumatoid arthritis patients from the Swiss Clinical Quality Management cohort were included in this study if they were in clinical remission, defined by 28-joint disease activity score (DAS28-ESR) <2.6, and had an available B-mode tenosynovitis score. The patients were stratified according to the presence or absence of tenosynovitis (USTS+ vs. USTS–). Cox proportional hazard models were used for time-to-event analysis until the loss of remission, after adjustment for multiple confounders. The impact of baseline US performed early in remission and the advent of flares at different fixed time periods after baseline were investigated in sensitivity analysis.ResultsTenosynovitis was detected in 10% of 402 rheumatoid arthritis patients in remission. At baseline, USTS+ patients in remission had significantly higher DAS28-ESR (mean (SD): USTS– 1.8 (0.5) versus USTS+ 2.0 (0.5); p = 0.0019) and higher additional disease activity parameters, such as physician global assessment, and simplified- and clinical-disease activity index. Joint synovitis detected by B-mode US was associated with tenosynovitis (mean (SD) 7.2 (6.3) in USTS– versus 9.0 (5.4) in USTS+, respectively; p = 0.02). A disease flare was observed in 69% of remission phases, with no differences in the time to loss of remission between USTS+ and USTS– groups.ConclusionWhile US-detected tenosynovitis was associated with higher disease activity parameters in rheumatoid arthritis patients in clinical remission, it was not able to predict a flare.

Cluster analysis identifies unmet healthcare needs among patients with rheumatoid arthritis

Objective To identify the patterns of healthcare resource utilization and unmet needs of persistent disease activity, pain, and physical disability in rheumatoid arthritis (RA) by cluster analysis. Method Patients attending the Jyväskylä Central Hospital rheumatology unit, Finland, were, from 2007, prospectively enrolled in a clinical database. We identified all RA patients in 2010–2014 and combined their individual-level data with well-recorded administrative data on all public healthcare contacts in fiscal year 2014. We ran agglomerative hierarchical clustering (Ward’s method), with 28-joint Disease Activity Score with three variables, Health Assessment Questionnaire index, pain (visual analogue scale 0–100), and total annual health service-related direct costs (€) as clustering variables. Results Complete-case analysis of 939 patients derived four clusters. Cluster C1 (remission and low costs, 550 patients) comprised relatively young patients with low costs, low disease activity, and minimal disability. C2 (chronic pain, disability, and fatigue, 269 patients) included those with the highest pain and fatigue levels, and disability was fairly common. C3 (inflammation, 97 patients) had rather high mean costs and the highest average disease activity, but lower average levels of pain and less disability than C2, highlighting the impact of effective treatment. C4 (comorbidities and high costs, 23 patients) was characterized by exceptionally high costs incurred by comorbidities. Conclusions The majority of RA patients had favourable outcomes and low costs. However, a large group of patients was distinguished by chronic pain, disability, and fatigue not unambiguously linked to disease activity. The highest healthcare costs were linked to high disease activity or comorbidities.

Inter-alpha-trypsin inhibitor heavy chain 4: A serologic marker relating to disease risk, activity, and treatment outcomes of rheumatoid arthritis.

ObjectiveInter‐alpha‐trypsin inhibitor heavy chain 4 (ITIH4) regulates immunity and inflammation, but its clinical role in rheumatoid arthritis (RA) patients remains unclear. Hence, this study was conducted to explore the association of circulating ITIH4 with disease risk, clinical features, inflammatory cytokines, and treatment outcomes of RA.MethodsAfter the enrollment of 93 active RA patients and 50 health controls (HCs), their serum ITIH4 level was analyzed by enzyme‐linked immunosorbent assay (ELISA). For RA patients only, serum ITIH4 level at week (W) 6 and W12 after treatment was also analyzed. Besides, serum tumor necrosis factor‐alpha (TNF‐α), interleukin (IL)‐1β, IL‐6, and IL‐17A at baseline of RA patients were also detected by ELISA.ResultsITIH4 was downregulated in RA patients (151.1 (interquartile range (IQR): 106.2–213.5) ng/mL) than in HCs (306.8 (IQR: 238.9–435.1) ng/mL) (p < 0.001). Furthermore, ITIH4 was negatively related to C‐reactive protein (CRP) (rs = −0.358, p < 0.001) and 28‐joint disease activity score using erythrocyte sedimentation rate (DAS28‐ESR) (rs = −0.253, p = 0.014) in RA patients, but not correlated with other clinical features (all p > 0.05). Besides, ITIH4 was negatively linked with TNF‐α (rs = −0.337, p = 0.001), IL‐6 (rs = −0.221, p = 0.033), and IL‐17A (rs = −0.368, p < 0.001) in RA patients, but not correlated with IL‐1β (rs = −0.195, p = 0.061). Moreover, ITIH4 was gradually elevated in RA patients from baseline to W12 after treatment (p < 0.001). Additionally, the increment of ITIH4 at W6 and W12 was linked with treatment response and remission in RA patients (all p < 0.05).ConclusionCirculating ITIH4 possesses clinical utility in monitoring disease risk, inflammation, disease activity, and treatment outcomes of RA.

Serum interleukin-6 in seropositive rheumatoid arthritis and response to tocilizumab: An observational study.

There is no clinically useful biomarker as a predictor of response to any class of biological disease-modifying antirheumatic drugs (bDMARD). Serum interleukin-6 (IL-6) has a major role in the pathogenesis of rheumatoid arthritis (RA) and its serum level in patients of RA may predict response to treatment with IL-6 receptor (IL-6R) antagonist tocilizumab. Biological DMARD naïve patients of seropositive RA, fulfilling American College of Rheumatology/European League Against Rheumatism classification criteria 2010, were treated with 06 doses of tocilizumab (8mg/kg) at monthly interval. Baseline and post-treatment serum IL-6 levels were measured and correlated with response to treatment measured by disease activity score-28 joints erythrocyte sedimentation rate (DAS28 ESR) after treatment. The study included 34 patients and 26 (70%) of them achieved DAS-28 remission (DAS28 ESR < 2.6). The baseline serum IL-6 did not correlate with post-treatment DAS28 ESR (R -0.197, P = .264). Though, statistically not significant (P = .085) more patients with comparatively lower baseline serum IL-6 attained DAS28 remission (16 out of 17, P = .085). There was an increase in the serum IL-6 level (median 40.5pg/ml [IQR 130.2] to 72.6pg/ml [IQR 162.5]) after tocilizumab treatment and the change in IL-6 level also did not correlate with post-treatment DAS28 ESR (R -0.240, P = .172). Higher number of patients with comparatively lower serum IL-6 level attained DAS28 remission in this study; however, it was not statistically significant. It requires further evaluation in larger studies to make any conclusion on the role of serum IL-6 as a predictor of response to tocilizumab in seropositive RA.