Disease-modifying Antirheumatic Drugs Group Research Articles

Factors determining resistance to conventional disease-modifying anti-rheumatic drug treatment in oligoarticular juvenile idiopathic arthritis.

Our study was designed to investigate the reasons for starting the conventional disease-modifying anti-rheumatic drugs (DMARDs) and the variables that impact the response to DMARD treatment in oligoarticular juvenile idiopathic arthritis (JIA) patients. Oligoarticular JIA patients (n = 187) were categorized into two groups: Group A consisted of patients who achieved remission with DMARD, and Group B comprised those who did not respond to DMARD therapy. DMARDs were initiated for various reasons: 68 (36.4%) due to active disease despite nonsteroidal anti-inflammatory drugs (± intra-articular corticosteroid) treatment, 59 (31.6%) due to uveitis, 49 (26.2%) due to extended oligoarticular JIA, and 11 (5.9%) due to inflammatory bowel disease. One hundred twenty-three patients (65.8%) achieved remission with DMARDs (Group A), while 64 patients (34.2%) did not respond to DMARD therapy (Group B). In Group B, patients had higher C-reactive protein (CRP) levels as well as higher Juvenile Idiopathic Arthritis Disease Activity Scores-71 (JADAS-71) at diagnosis (both p < 0.001). Moreover, extended oligoarticular JIA subtype (p = 0.017) and involvement of small joints at diagnosis (p = 0.043) were more prevalent among these patients. Group A exhibited a higher frequency of antinuclear antibody positivity (p = 0.014). Elevated CRP levels (> 1.1mg/dL) (OR 1.308, 95% CI 1.203-3.574; p < 0.001) and high JADAS-71 at diagnosis (> 15.8) (OR 1.659, 95% CI 1.179-2.941; p < 0.001) were associated with DMARD resistance. Elevated CRP and high JADAS-71 at diagnosis were the main factors associated with DMARD resistance in oligoarticular JIA. Prospective long-term studies may help verify the role of these factors associated with DMARD resistance in oligoarticular JIA. Key Points • Conventional DMARDs were most commonly started due to active disease despite NSAID (± intra-articular corticosteroids). • Remission was achieved with DMARD in 65.8% of oligoarticular JIA patients. • Elevated CRP and high JADAS-71 at diagnosis were associated with DMARD resistance.

Effects of tapering conventional synthetic disease-modifying antirheumatic drugs to drug-free remission versus stable treatment in rheumatoid arthritis (ARCTIC REWIND): 3-year results from an open-label, randomised controlled, non-inferiority trial

Tapering of disease-modifying antirheumatic drugs (DMARDs) to drug-free remission is an attractive treatment goal for patients with rheumatoid arthritis, although long-term effects of tapering and withdrawal remain unclear. We compared 3-year risks of flare between three conventional synthetic DMARD treatment strategies in patients with rheumatoid arthritis in sustained remission. In this open-label, randomised controlled, non-inferiority trial, we enrolled patients aged 18-80 years with rheumatoid arthritis who had been in sustained remission for at least 1 year on stable conventional synthetic DMARD therapy. Patients from ten hospitals in Norway were randomly assigned (2:1:1) with centre stratification to receive stable conventional synthetic DMARDs, half-dose conventional synthetic DMARDs, or half-dose conventional synthetic DMARDs for 1 year followed by withdrawal of all conventional synthetic DMARDs. The primary endpoint of this part of the study was disease flare over 3 years, analysed as flare-free survival and risk difference in the per-protocol population with a non-inferiority margin of 20%. This trial is registered with ClinicalTrials.gov (NCT01881308) and is completed. Between June 17, 2013, and June 18, 2018, 160 patients were enrolled and randomly assigned to receive stable-dose conventional synthetic DMARDs (n=80), half-dose conventional synthetic DMARDs (n=42), or half-dose conventional synthetic DMARDs tapering to withdrawal (n=38). Four patients did not receive the intervention and 156 patients received the allocated treatment strategy. One patient was excluded due to major protocol violation and 155 patients were included in the per-protocol analysis. 104 (67%) of 156 patients were women and 52 (33%) were men. 139 patients completed 3-years follow-up without major protocol violation; 68 (87%) of 78 patients in the stable-dose group, 36 (88%) of 41 patients in the half-dose group and 35 (95%) of 37 patients in the half-dose tapering to withdrawal group. During the 3-year study period, 80% (95% CI 69-88%) were flare-free in the stable-dose group, compared with 57% (41-71%) in the half-dose group and 38% (22-53%) in the half-dose tapering to withdrawal group. Compared with stable-dose conventional synthetic DMARDs, the risk difference of flare was 23% (95% CI 6-41%, p=0·010) in the half-dose group and 40% (22-58%, p<0·0001) in the half-dose tapering to withdrawal group, non-inferiority was therefore not shown. Adverse events were reported in 65 (83%) of 78 patients in the stable-dose group, 36 (90%) of 40 patients in the half-dose group, and 36 (97%) of 37 patients in the half-dose tapering to withdrawal group. One death occurred in the stable-dose conventional synthetic DMARD group (sudden death considered unlikely related to the study medication). Two conventional synthetic DMARD tapering strategies were associated with significantly lower rates of flare-free survival compared with stable conventional synthetic DMARD treatment, and the data do not support non-inferiority. However, drug-free remission was achiveable for a significant subgroup of patients. This trial provides information on risk and benefits of different treatment strategies important for shared decision making. Research Council of Norway and South-Eastern Norway Regional Health Authority.

A clinical study on the risk and safety profiles of NSAIDs used for osteoporotic fractures in Chinese patients with rheumatoid arthritis

Purpose: To investigate the risk and safety profile of non-steroidal anti-inflammatory drugs (NSAIDs) for osteoporotic fractures in patients with rheumatoid arthritis (RA). &#x0D; Methods: 298 RA patients admitted to The First People's Hospital of Huzhou, Huzhou, China from August 2020 to September 2022, were investigated. Patients were assigned to groups based on drugs used viz: control group received anti-rheumatic drugs other than NSAIDs; corticosteroid group received dexamethasone, disease-modifying anti-rheumatic drugs (DMARDs) groups received sulfasalazine, NSAID group received either diclofenac or ibuprofen etc. Each group of patients received the respective treatment frequently for at least 3 years. The primary outcome in this study was the incidence of osteoporotic fracture resulting from fragile bone and deterioration of bone mass. &#x0D; Results: The incidence of osteoporotic fracture was highest in NSAID group (11.58 %) when compared to 5.44, 4.96, and 2.36 % in the corticosteroid, DMARD and control groups, respectively (p &lt; 0.05). This shows that users of NSAIDs had a 5-fold higher risk of osteoporotic fracture than patients in control group (OR = 1.26 (95 % CI: 1.22 - 1.81)) and 2-fold possibility of osteoporotic fracture when compared to corticosteroid users ((OR = 1.46 (95 % CI: 1.57 - 2.32)) and DMARD users (1.83 (95 % CI: 1.26 - 1.67)). &#x0D; Conclusion: Rheumatoid arthritis patients on NSAIDs such as celecoxib, diclofenac, ibuprofen, indomethacin, and oxaprozin are at risk of developing osteoporotic fracture. Therefore, NSAIDs must be used with proper counseling in RA patients to minimize the risk of osteoporotic fracture. In future, the study duration will need to be extended to determine the long-term effects and potential changes in bone properties.

The economic burden of biologic disease-modifying antirheumatic drugs in rheumatoid arthritis patients in the United States

Background Previous U.S. economic burden estimates for rheumatoid arthritis (RA) varied from $85.6 to 148.1 billion annually. However, these estimates do not reflect comparative amounts spent on RA treatment options in addition to other medical expenditures. Therefore, this study’s goal was to comparatively analyze the overall economic burden of U.S. patients treated for RA using conventional disease-modifying antirheumatic drugs (DMARDs) versus TNF alpha biologic DMARDs. Research Design and Methods This retrospective observational study analyzed Medical Expenditure Panel Survey Household Component data from 2016 to 2018. Healthcare utilization, total medical expenditures, and out-of-pocket expenditures were compared between RA medication groups. Results Three hundred twenty-five adult RA patients experiencing 603 RA-related events, including at least one medical visit, between 2016 and 2018 were identified. Rheumatic arthritis-attributable medical expenditures among patients prescribed DMARDs were $11.4 billion. Average total medical expenditures were significantly higher for the TNF alpha biologic group $26,216.67 (95% CI: $19,502.84–$32,930.5) versus $5,388.52 (95% CI: $2,768.25–$8,008.79) for the conventional DMARD group (p<0.001). Conclusions RA patients receiving TNF alpha biologics experienced significantly higher total medical and out-of-pocket expenditures; however, they have experienced fewer or no occurrences of high-cost drivers of healthcare utilization compared to patients receiving conventional DMARDs.

Non-biologic, steroid-sparing therapies for non-infectious intermediate, posterior, and panuveitis in adults.

Non-biologic, steroid-sparing therapies for non-infectious intermediate, posterior, and panuveitis in adults.

B cell depletion in patients with rheumatoid arthritis is associated with reduced IL-1β in GCF.

We evaluated the effect of B cell depletion on the clinical periodontal findings and IL-1β and MMP-8 levels of the gingival crevicular (GCF) fluid in patients with rheumatoid arthritis (RA). Seventy patients were included in this case-control study. Twenty patients with RA were undergoing B-cell depletion treatment. The second group of RA patients (n = 20) were undergoing non-B-cell depletion treatment with Disease-Modifying Anti-Rheumatic Drugs (DMARD). Control group, with no RA, consisted of 30 individuals. Periodontal parameters including probing depth (PD), clinical attachment level (CAL), bleeding on probing (BOP), gingival index (GI), and plaque index (PI) were recorded. IL-1β and MMP-8 levels in GCF were determined using enzyme-linked immunosorbent assay. Rheumatological parameters including Disease Activity Score-28 (DAS-28), rheumatoid factor levels (RF), and anti-cyclic citrullinated peptide levels were included in the data analyses. All groups were similar in PD, CAL, BOP, GI, and PI measures. GCF IL-1β levels were 1.85 ± 1.67pg in the B-cell depletion group, 10.50 ± 13.16pg in the DMARD group, and 34.12 ± 29.45pg in the control group (p < 0.001). MMP-8 levels were 21.00 ± 4.23pg in the B-cell depletion group, 8.16 ± 6.94pg in the DMARD group, and 21.45 ± 8.67pg in the control group (p < 0.001). DAS 28, RF, and anti-CCP were similar in RA groups. GCF IL-1β levels were significantly lower in B cell depletion group, and MMP-8 levels were significantly lower in DMARD group, suggesting that rheumatoid arthritis treatments may modify biochemical parameters of GCF. This study suggests that host modulation therapies in RA can reduce local production of IL-1β and MMP-8. Reduction of these inflammatory cytokines and enzymes may have a beneficial effect in controlling periodontal tissue destruction.

Modified Hidden Blood Loss Based on Drainage in Posterior Surgery on Lumbar Stenosis Syndrome with Rheumatoid Arthritis.

ObjectivePublications on hidden blood loss (HBL) after posterior lumbar interbody fusion (PLIF) for lumbar spine stenosis syndrome (LSS) have been reported, but the modified HBL (mHBL) was different from HBL obtained by classical formula and there are few studies on lumbar spine hemorrhage with rheumatoid arthritis (RA). Therefore, the aim of our study is to respectively evaluate the importance of hidden blood loss (HBL) and modified HBL (mHBL) after posterior lumbar interbody fusion (PLIF) in patients diagnosed with LSS and RA, to explore the correlation between RA activity and HBL as well as mHBL.MethodsA total of 61 patients (nine males and 52 females) diagnosed with LSS and RA who underwent PLIF were included. Data contained demographics, RA‐related parameters such as duration of RA, Steinbrocker classification (used to evaluated RA activity), the disease‐modifying anti‐rheumatic drugs (DMARDs), osteoporosis and total knee arthroplasty; operation and hemorrhage parameters. Then HBL and mHBL were calculated by Gross formula and modified formula, respectively. Subgroup analysis on HBL and mHBL was performed based on gender, age (≤60 years and ˃60 years), different number of surgical segments (single segment, double segment, and ≥3 segments), and taking DMARDs or not. ANOVA analysis was performed on HBL and mHBL in different surgery segment number and Steinbrocker classification of RA. Independent sample t‐test was used in comparison of gender and age, as well as in comparison between HBL and mHBL based on whether the patient took DMARDs or not. Furthermore, paired t‐test was used to compare the volume between HBL and mHBL.ResultsThe mean age and duration of RA was 65.2 ± 9.3 years and 14.3 ± 10.7 years, respectively. There were 13 grade I cases, 34 grade II cases, and 14 grade III cases as assessed by Steinbrocker classification and the most common anti‐RA drugs were DMARDs (57.4%). The mean intraoperative bleeding, drainage, and blood loss in drainage (DBL) was 453.3 ± 377.8 mL, 489.1 ± 253.8 mL, and 304.6 ± 156.3 mL, respectively. There was no difference on HBL and mHBL in gender. HBL and mHBL was larger in patients over 60 years (P = 0.040 and P = 0.023). There were differences in intraoperative blood loss, drainage, and DBL based on different number of segments but not in HBL and mHBL, or on Steinbrocker classification. DBL was lower in DMARDs group than non‐drugged group (P = 0.03), while HBL and mHBL were both of no significance. The comparison of HBL and mHBL showed statistical difference (P < 0.001), suggesting that mHBL volume is larger than HBL.ConclusionsPatients diagnosed as LSS with RA have amounts of HBL or mHBL after PLIF. HBL or mHBL is not associated with RA activity, which may not increase in RA patients compared with common ones. Taking DMARDs may reduce postoperative DBL. The fact that mHBL is larger than HBL provides an all‐round basis for measuring factual HBL.

Patients With Rheumatoid Arthritis With an Inadequate Response to Disease-Modifying Antirheumatic Drugs at a Higher Risk of Acute Coronary Syndrome.

BackgroundCardiovascular disease is the most common cause of death in patients with rheumatoid arthritis. It is believed that using disease‐modifying antirheumatic drugs (DMARDs) to control inflammation can reduce the risk of cardiovascular disease. In this study, we investigated whether patients who responded differently to DMARDs might sustain different cardiovascular events.Methods and ResultsWe designed a cohort study using the Chang Gung Research Database. We identified 7114 patients diagnosed with rheumatoid arthritis. After strict exclusion criteria, we collected 663 individuals as an inadequate response to DMARDs group. Then, 2034 individuals were included as the control group. The end point was composite vascular outcomes, including acute coronary syndrome or ischemic stroke. We used the inverse probability of treatment weighting to keep the covariates between these 2 groups well balanced. We compared the risk of these outcomes using the Cox proportional hazards model. The mean follow‐up time was 4.7 years. During follow‐up, there were 7.5% and 6.4% of patients with composite vascular outcomes in the DMARD‐inadequate response and control groups, respectively. There was no significant difference in the risk of composite vascular outcomes (95% CI, 0.94–1.41) and ischemic stroke (95% CI, 0.84–1.36). The risk of acute coronary syndrome was significantly higher in the DMARD‐inadequate response group (hazard ratio, 1.45; 95% CI, 1.02–2.05).ConclusionsPatients with DMARD‐inadequate response rheumatoid arthritis have a higher risk of developing acute coronary syndrome than those whose disease can be controlled by DMARDs.

Better clinical outcome of total knee arthroplasty for rheumatoid arthritis with perioperative glucocorticoids and disease-modifying anti-rheumatic drugs after an average of 11.4-year follow-up

BackgroundPrevious evidence suggested that perioperative anti-rheumatic therapy for patients receiving total knee arthroplasty (TKA) helped improve postoperative rehabilitation for rheumatoid arthritis (RA), yet long-term effects and outcomes of perioperative drug therapy in TKA presently remain unclear. This study investigated whether perioperative treatment with glucocorticoids (GC) and disease-modifying anti-rheumatic drugs (DMARDs) can improve clinical outcomes for patients with RA undergoing TKA.MethodsPatients between January 2000 and December 2011 were allocated into three groups based on perioperative drug therapy: A, control group (no GC or DMARDs), B, DMARD group (DMARDs given without GC), and C, co-therapy group (DMARDs plus GC). The patients were followed up for average 11.4 years. Baseline characteristics, pre- and post-operative Hospital for Special Surgery score (HSS), laboratory parameters, and complications were recorded by follow-up.ResultsFifty-six RA patients undergoing 91 TKAs were included in this study. Patients who received perioperative GC with DMARDs (group C) achieved larger/increased range of motion (ROM) (C:122.17 vs A:108.31 vs B:108.07, p = 0.001, partial eta squared (η2 p) = 0.18) at 1 year, better HSS score (C, 83.01 vs A, 79.23 vs B, 77.35, p = 0.049, η2 p = 0.067), pain relief (C, 1.09 vs A, 1.17 vs B, 1.75, p = 0.02, η2 p = 0.094), and ROM (C, 130.81 vs A, 112.82 vs B, 113.58, p = 0.001, η2p = 0.142) at latest follow-up comparing with the other treatment groups. No differences were noted in laboratory tests, blood loss, volume of transfusion, or complications among groups.ConclusionsCompared with the other perioperative anti-rheumatic treatments, the combination of GC and DMARDs results in improved HSS score, better function, larger range of motion, and reduced postoperative pain for TKA patients with RA in the long term. Further investigation is warranted to look for a better understanding of more specific medication effects and strike a good balance between the benefits and complications for long-term pharmacotherapy.

Evaluation of the immune response to hepatitis B vaccine in patients on biological therapy: results of the RIER cohort study.

To evaluate the response to hepatitis B virus (HBV) vaccine in patients on biological therapy. Adults with autoimmune inflammatory diseases on biological therapy such as anti-TNFα, rituximab, tocilizumab, abatacept, or anakinra were included. Hepatitis B surface antibody (anti-HBs) was measured by ELISA before and after vaccination. Seroconversion was considered when an anti-HBs titer > 10mIU/mL was achieved. The effect of treatment on the immunoprotective state was studied. The response was compared with that obtained in patients on synthetic disease modifying anti-rheumatic drugs (DMARDs) and healthy controls. A total of 187 patients on biologicals, 48 on synthetic DMARDs, and 49 on healthy controls were analyzed. More than 80% of patients on biologics responded to the vaccine but required more boosters and second vaccine series. Patients who achieved seroconversion were younger than those who did not (47.10 ± 12.99 vs. 53.18 ± 10.54years, p = 0.012). Being on etanercept or golimumab was associated with seroconversion, while being on rituximab was not. Seroconversion was achieved in 93.75% of patients on synthetic DMARDs and 97.96% of healthy controls. The seroconversion rate in the biologics group was lower than in the synthetic DMARD group (p = 0.043) and tended to be lower than in the healthy group (p = 0.056). In patients on biological therapy, a high rate of HBV vaccine response can be achieved when a complete vaccination schedule is administered. Vaccination while not on biological agents reduces the requirement for boosters and revaccination. Key points: • Patients on biological therapy can achieve high rates of immune response to HBV vaccine when complete vaccination schedules are administered. • However, to achieve such a high seroconversion rate, more boosters and second vaccination series are required. • This supports the proposal already made to provide HBV vaccination to all patients with an autoimmune inflammatory disease after the diagnosis is made and not when the use of a biological treatment is under consideration.

Response to tocilizumab and work productivity in patients with rheumatoid arthritis: 2-year follow-up of FIRST ACT-SC study

Objectives We evaluated long-term control of rheumatoid arthritis (RA) in Japanese paid workers (PWs) and house workers (HWs) treated with subcutaneous tocilizumab (TCZ-SC) and explored factors affecting response to TCZ-SC regarding work productivity. Methods This study collected data from patients with RA in the TCZ-SC +/− conventional synthetic disease-modifying antirheumatic drugs group. Factors affecting the response to tocilizumab regarding work productivity were explored using logistic regression. Differences in quality-adjusted life years (QALYs) between with/without response were analysed by a linear regression. Results Data were analysed for 357/360 patients. Patients with a ≥ 75% improvement in activity impairment (AI) were considered responders. EuroQol-5 Dimension (EQ-5D), six-item Kessler psychological distress scale score (K6), Health Assessment Questionnaire Disability Index (HAQ-DI), and the patient’s disease global health by visual analogue scale were significant contributors to TCZ-SC response based on improvements in AI. Work Functioning Impairment Scale, presenteeism, EQ-5D, K6, and HAQ-DI significantly contributed to the improvement of overall work impairment in PWs. Shorter disease duration also was related to TCZ-SC response based on AI improvements. Responders had significantly larger mean QALYs than non-responders (difference = 0.2614; p < .001). Conclusions These real-world clinical data support long-term work productivity control with TCZ-SC for biologic-naïve HWs and PWs with RA.

Cost-effectiveness analysis of etanercept plus methotrexate vs triple therapy in treating Chinese rheumatoid arthritis patients.

Objective:This study aimed to explore the cost-effectiveness of etanercept plus methotrexate (ETN+MTX) compared to triple disease-modifying anti-rheumatic drugs (DMARDs) in treating Chinese rheumatoid arthritis (RA) patients.Methods:The 134 Chinese RA patients who were about to initiate ETN+MTX or triple DMARDs therapy based on treat-to-target strategy were consecutively recruited and categorized into ETN+MTX group (N = 49) or triple DMARDs group (N = 85). Treatment efficacy was assessed at month 3 (M3)/M6/M9/M12 after initiation of treatment. Also, 1-year treatment cost was evaluated, and cost-effectiveness analysis and sensitivity analysis were conducted.Results:RA patients in ETN+MTX group exhibited similar disease activity and quality of life at each time point while elevated 28-joint disease activity score based on erythrocyte sedimentation rate (DAS28-ESR) change (M0-M12) and low disease activity rate compared with triple DMARDs group. For 1-year treatment cost, ETN+MTX required increased drug cost, decreased other medical cost, and finally elevated total cost compared with triple DMARDs. Meanwhile, compared to triple DMARDs, ETN+MTX produced an additional quality-adjusted life year (QALY) of 0.015, resulting in an incremental cost-effectiveness ratio (ICER) of ¥2,939,506.7 per QALY that was 53.1 folds of gross domestic product (GDP) per capita in China. More interestingly, sensitivity analysis revealed that the ETN price had to be reduced at least by 71.3% before ETN+MTX became cost-effectiveness compared to triple DMARDs.Conclusion:ETN+MTX is less cost-effective in treating Chinese RA patients compared with triple DMARDs.

Risk of Serious Infection in Patients With Rheumatoid Arthritis Treated With Biologic Versus Nonbiologic Disease-Modifying Antirheumatic Drugs.

ObjectiveThe objective of this study is to examine the risk of serious infections (SIs) associated with biological disease‐modifying antirheumatic drugs (bDMARDs) compared with conventional synthetic disease‐modifying antirheumatic drugs (csDMARDs) in patients with rheumatoid arthritis (RA).MethodsWe studied patients with RA who initiated bDMARDs or csDMARDs from 2001 to 2016 in FORWARD–The National Databank for Rheumatic Diseases. Disease‐modifying antirheumatic drugs (DMARDs) were categorized into three groups: (1) csDMARDs (bDMARD‐naïve; reference), (2) tumor necrosis factor α inhibitors (TNFis), and (3) non‐TNFi biologics (abatacept, rituximab, tocilizumab, and anakinra). SIs were defined as those requiring intravenous antibiotics or hospitalization or those resulting in death. We calculated the propensity score (PS), which reflected the probability of receiving a specific DMARD group, and estimated the hazard ratio (HR) (with the 95% confidence interval [CI]) for SI from multivariable Cox models, adjusting for PS and time‐varying confounders.ResultsA total of 694 (5.9%) first SIs were identified in 11 623 patients with RA during 27 552 patient‐years of follow‐up. The SI incidence rate per 1000 patient‐years was 22.4 (95% CI 19.2‐26.1) for csDMARDs, 26.9 (95% CI 24.5‐29.6) for TNFis, and 23.3 (95% CI 19.0‐28.5) for non‐TNFi bDMARDs. Adjusted HRs for SIs were 1.33 (95% CI 1.05‐1.68) for TNFis and 1.48 (95% CI 1.02‐2.16) for non‐TNFi bDMARDs, compared with csDMARDs. The SI risk with non‐TNFi bDMARDs versus TNFis was not different. Other risk factors for SI were older age, higher comorbidity burden (particularly pulmonary disease), higher weighted cumulative prednisone dose, disability and disease activity, and number of prior csDMARD failures.Conclusion TNFis and non‐TNFi bDMARDs were associated with an increased SI risk compared with csDMARDs in RA, even after accounting for risk‐associated patient characteristics.

Use of disease-modifying anti-rheumatic or anti-tumour necrosis factor drugs and risk of hospitalized infection in ankylosing spondylitis

Objective: To assess the risk of hospitalized infection among initiators of disease-modifying anti-rheumatic drugs (DMARDs) and/or anti-tumour necrosis factor (anti-TNF) agents in ankylosing spondylitis (AS).Method: We studied AS patients, new users of anti-TNF drugs and/or DMARDs between 1 January 2001 and 31 December 2011. Cohort entry was defined as the date of first prescription of any of these drugs. We used Cox regression with three time-varying drug exposures: current use of DMARDs without biologics, current use of anti-TNF agents alone or in combination with DMARDs (anti-TNF ± DMARDs), and current non-use. Models were adjusted for baseline patient sociodemographic characteristics, comorbidity, outpatient visits and procedures, previous infection, non-steroidal anti-inflammatory drugs, and corticosteroids. Hospitalized infection was defined on the basis of hospitalization discharge diagnoses (primary or non-primary) coding for infection.Results: The cohort included 747 AS patients, with a mean age of 51.1 years (sd 14.6), and 466 (62.4%) were men. During the median follow-up of 1.98 years, 57 hospitalized infections occurred, for an incidence rate of 2.9/100 person-years. The adjusted hazard ratio of infection (relative to unexposed) was 1.00 [95% confidence interval (CI) 0.47–2.11] for the anti-TNF ± DMARDs group and 0.96 (95% CI 0.45–2.04) for DMARDs alone. Use of healthcare, corticosteroids, and previous hospitalized infections were associated with infection.Conclusion: We found no clear evidence that the risk of hospitalized infection was linked to DMARD and/or anti-TNF drug use. Because of scarce published literature on infection risk in AS patients, our results have important implications for clinicians.

Refining a Claims-based Algorithm to Estimate Biologic Medication Effectiveness and Cost per Effectively Treated Patient with Rheumatoid Arthritis.

Claims data generally lack information on clinical outcomes. However, a validated claims-based algorithm for estimating the effectiveness of biologic agents in treating rheumatoid arthritis (RA) was recently developed and applied to various databases. The objectives of the study were to implement a claims-based algorithm in a large nationwide database to estimate medication effectiveness and cost for patients with RA using biologic disease-modifying antirheumatic drugs (DMARDs) and to assess the effect of eliminating one criterion from the algorithm on results. The DMARD groups included patients initiated on etanercept, adalimumab, abatacept, or infliximab. Patients were categorized as effectively treated if they met these six criteria: a medication possession ratio of 80% or greater; no escalation in biologic dose; no switch in biologics; no new nonbiologic DMARD; no new or increased oral glucocorticoid treatment; and no more than one glucocorticoid injection. In a follow-up analysis, the dose-escalation criterion was removed because an increase in dose for infliximab may be appropriate. Average costs for RA-related medications were calculated for each DMARD patient group and divided by the number of patients who met all six effectiveness criteria. A total of 1196 individuals were included in the analysis. Using the algorithm, the index biologic was categorized as effective for 25.4% of patients overall: 30.3% (102/337) of etanercept, 27.6% (104/377) of adalimumab, 32.7% (37/113) of abatacept, and 16.5% (61/369) of infliximab patients. Total costs for RA medication costs per effectively treated patient ranged from more than $80,000 for infliximab to ~$43,000-$46,000 for the other three groups. Removing the no dose-escalation criterion drastically reduced the cost per effectively treated patient in the infliximab group (to ~$42,000). Using the original six-criteria claims-based algorithm in a large claims database, infliximab was the least-effective biologic agent and had the highest medication cost per effectively treated patient. However, when a follow-up analysis removed the dose-escalation exclusion criterion, the four groups had similar effectiveness and medication costs per effectively treated patient with RA.

Risk of tuberculosis comparison in new users of antitumour necrosis factor-α and with existing disease-modifying antirheumatic drug therapy.

Patients with rheumatic disease are at risk for infections. Evaluating antitumour necrosis factor (anti-TNF) drug-associated risk of infections requires justification of baseline risk in the population at high risk of infection. We examined the incidence of active tuberculosis (TB) and its risk factors in patients with rheumatic disease started with anti-TNF-α therapy or with existing disease-modifying antirheumatic drug (DMARD) therapy. A retrospective cohort study of anti-TNF-α therapy new users (anti-TNF-α group) and those starting with a DMARD after the failure of at least one other DMARD or who had added to existing DMARD treatment (DMARD group) for rheumatic disease in the largest medical setting in Taiwan from 1 January 2005 through 31 November 2013 was conducted to determine relative risk of TB between patient groups. Patients in the DMARD group were stratified into "mild" and "severe" disease severity as proxies for low and high background risk of infection. A total of 3640 patients were enrolled (anti-TNF: 955; DMARD: 2685). The incidence of TB was 903.9/100000 patient-years for anti-TNF-α new users and 391.7/100000 patient-years for DMARD switchers. In Cox regression model, adjusted HR for TB in the anti-TNF-α group was higher than for the entire DMARD group (aHR, 2.41; 95% confidence interval [CI], 1.2-4.85), subgroup with mild disease (2.91; 1.31-6.47) and subgroup with severe disease (1.65; 0.68-4.03). Significant independent risk factors for TB were being male, age ≥60years, history of respiratory disease, glucocorticoids dose >7.5mg/d and living in a TB-prevalent region. Anti-TNF-α therapy was independently associated with increased risk of TB in patients with mild disease, but it was not significantly correlated in patients with severe disease after adjusting for confounders.

The Temporal Relationship between Arterial Stiffening and Blood Pressure Is Modified by Methotrexate Treatment in Patients with Rheumatoid Arthritis.

Background: The temporal relationship between arterial stiffness and blood pressure (BP) may vary depending on age and other clinical and demographic factors. Since both BP and arterial stiffness are also affected by inflammatory processes, we examined the temporal arterial stiffness-BP relationship in patients with rheumatoid arthritis (RA) treated with either methotrexate (MTX), an anti-rheumatic agent shown to reduce cardiovascular risk in meta-analyses, or other disease-modifying anti-rheumatic drugs (DMARDs).Methods: Measurements of clinic and 24-h peripheral and central systolic and diastolic BP (SBP and DBP), and pulse wave velocity (PWV) were assessed in RA patients on stable treatment with either MTX ± other DMARDs (MTX group, n = 41, age 61 ± 14 years, 73% females) or other DMARDs (non-MTX group, n = 18, age 65 ± 13 years, 89% females). Measurements were performed at baseline and after 8 months. The temporal relationships were examined using cross-lagged path analysis with models that included age, sex, body mass index, prednisolone, and folic acid use and 28-joint disease activity score.Results: There were significant differences in the temporal arterial stiffness-BP relationships between those in the MTX and DMARD groups. A higher PWV at baseline caused a significant increase in 6 out of 8 different measures of SBP at 8 months amongst those treated with DMARDs (standardized β, range = 0.54–0.66, p < 0.003 for each) and 3 out of 8 different measures of DBP (standardized β, range = 0.52–0.61, p < 0.003 for each) but was not associated with either SBP or DBP at 8 months amongst those treated with MTX. The difference in the effect of baseline PWV on 8-month BP between the 2 groups was also significant (p < 0.003) for 4 measures including clinic peripheral SBP (β = 7.0, 95% CI = 2.8–11.1 mmHg per 1 m/s higher baseline PWV; p < 0.001).Conclusions: Higher arterial stiffness preceded increases in BP in subjects with RA treated with DMARDs, but these effects did not occur amongst those treated with MTX. The different effects were seen mostly in measures of SBP but were also present in some measures of DBP. Our findings suggest MTX may confer a protective effect against stiffness mediated increases in BP in patients with RA.

New inflammatory markers in early rheumatoid arthritis.

Rheumatoid arthritis (RA) is the most common chronic inflammatory disorder and is associated with progressive destruction of synovial joints and physical disability. Therapies with known benefits include disease-modifying antirheumatic drugs (DMARDs), such as methotrexate, as well as more recent biologic agents, such as tumor necrosis factor inhibitors (anti-TNF therapy). This was aretrospective study, which included 205 RA and 112 early RA (ERA) patients from the Rheumatology Clinic at Gaziantep University School of Medicine Research Center as well as 104 healthy controls. The mean neutrophil to lymphocyte ratio (NLR) was found to be 3.15± 2.64 in the patient group and 2.03± 0.94 in the control group. The mean platelet to lymphocyte ratio (PLR) was 162.39± 107.76 in the patient group and 131.23± 48.09 in the control group. There was asignificant difference in both the NLR and PLR between the patient and control groups (both p< 0.01). There was asignificant difference in both the NLR and PLR between patients with active disease and remission (both p< 0.001) in RA, including anti-TNF therapy and DMARDs groups. There was asignificant difference in NLR (p= 0.001) but not in PLR (p= 0.051) between active disease and remission in ERA. The results of the present study suggest that the NLR may be considered auseful marker of disease activity in RA and one that can aid the diagnosis of ERA. The PLR can be used in the assessment of disease activity in RA patients undergoing anti-TNF therapy but is not suitable for diagnosing ERA.

Relation among anti-rheumatic drug therapy, CD14+CD16+ blood monocytes and disease activity markers (DAS28 and US7 scores) in rheumatoid arthritis: A pilot study

Circulating human monocytes, a functionally and phenotypically heterogeneous population, are emerging as fundamental cell types in rheumatoid arthritis (RA). The aim of this pilot study was to assess the correlation, if any, among anti-rheumatic drug therapy, circulating CD14+CD16+ monocytes and validated clinical scales (e.g., DAS28 score and ultrasonography US7 score) of disease severity in RA. Thirty consecutive RA patients, either naïve or under disease-modifying anti-rheumatic drugs (DMARDs) or biological therapy, and 10 age-matched healthy volunteers, were enrolled. Monocytes were prepared from heparinized blood samples; surface expression of CD14 and CD16 was determined by flow cytometry. RA patients presented a significantly higher percentage of CD14+CD16+ monocytes, as compared to healthy subjects. There was a good correlation between DAS28 clinical score and the ultrasound composite score US7 (r=0.66), as well as between both scores and the percentage of CD14+CD16+ monocytes (r=0.43 and 0.47, respectively). Naïve RA patients had the highest expression (19.2±3.2%) of CD14+CD16+ monocytes and elevated DAS28 score; patients on DMARDs presented a 7-fold increased expression of CD14+CD16+ monocytes, relatively to healthy volunteers (2.1±1.4%), and an intermediate disease severity. The RA patients treated with biological therapy had a low percentage of CD14+CD16+ monocytes (5.1±3.6%; p<0.01 vs naïve and DMARDs groups), similar to the one detected in healthy controls, and reduced US7 and DAS28 scores. Interestingly, for the same DAS28 score, monocytes isolated from RA patients on biological therapy had a lower CD16 expression than patients on DMARDs.Therefore, CD14+CD16+ circulating blood monocytes may represent an appropriate biomarker to assess RA disease activity along with DAS28 and US7 scores. Together, these three parameters may represent a better indicator for evaluating therapy efficacy.

Treatment persistence in patients with rheumatoid arthritis and ankylosing spondylitis.

ABSTRACTOBJECTIVE To evaluate treatment persistence in patients with rheumatoid arthritis and ankylosing spondylitis who started therapies with disease-modifying antirheumatic drugs (DMARD) and tumor necrosis factor blockers (anti-TNF drugs).METHODS This retrospective cohort study from July 2008 to September 2013 evaluated therapy persistence, which is defined as the period between the start of treatment until it is discontinued, allowing for an interval of up to 30 days between the prescription end and the start of the next prescription. Odds ratio (OR) with 95% confidence intervals (95%CI) were calculated by logistic regression models to estimate the patients’ chances of persisting in their therapies after the first and after the two first years of follow-up.RESULTS The study included 11,642 patients with rheumatoid arthritis – 2,241 of these started on anti-TNF drugs (+/-DMARD) and 9,401 patients started on DMARD – and 1,251 patients with ankylosing spondylitis – 976 of them were started on anti-TNF drugs (+/-DMARD) and 275 were started on DMARD. In the first year of follow-up, 63.5% of the patients persisted in their therapies with anti-TNF drugs (+/-DMARD) and 54.1% remained using DMARD in the group with rheumatoid arthritis. In regards to ankylosing spondylitis, 79.0% of the subjects in anti-TNF (+/-DMARD) group and 41.1% of the subjects in the DMARD group persisted with their treatments. The OR (95%CI) for therapy persistence was 1.50 (1.34-1.67) for the anti-TNF (+/-DMARD) group as compared with the DMARD group in the first year for the patients with rheumatoid arthritis, and 2.33 (1.74-3.11) for the patients with ankylosing spondylitis. A similar trend was observed at the end of the second year.CONCLUSIONS A general trend of higher rates of therapy persistence with anti-TNF drugs (+/-DMARD) was observed as compared to DMARD in the study period. We observed higher persistence rates for anti-TNF drugs (+/-DMARD) in patients with ankylosing spondylitis as compared to rheumatoid arthritis; and a higher persistence for DMARD in patients with rheumatoid arthritis as compared to ankylosing spondylitis.