Disease-modifying Antirheumatic Drugs Users Research Articles

Long-term antibody responses to COVAXIN and COVISHIELD vaccines in rheumatoid arthritis patients and healthy control population – A cross-sectional study

ABSTRACT Background: Rheumatoid arthritis (RA) is a chronic autoimmune disease that causes inflammation and damage in the joints. It often requires treatment with disease-modifying antirheumatic drugs (DMARDs) to manage symptoms and prevent progression. The study investigates the long-term antibody responses to COVAXIN and COVISHIELD vaccines in RA patients. Methodology: This cross-sectional study (IEC approval no: AlIMS/BBN/IEC/AUG/2021/60-R dated Sept 05, 2022, and Ref No: 799/U/IEC/ESICMC/F490/09/2022 dated Oct 31, 2022) enrolled 103 diagnosed RA patients receiving DMARDs and 183 healthy controls. The participants who completed 1 year after the second dose of vaccination were included, and detailed information on demographic, medical, and vaccination were collected. Laboratory investigations included complete blood count, inflammatory markers, and antispike antibody levels. Statistical analyses assessed differences between COVAXIN and COVISHIELD subgroups, considering DMARDs usage and disease duration. Results: Among RA patients, both COVAXIN and COVISHIELD groups exhibited low disease activity. No significant (P > 0.05) differences were found in IL-6, CRP, or antispike antibody levels between COVAXIN and COVISHIELD subgroups in RA patients and healthy controls. Notably, 89% of female RA patients received COVISHIELD. Co-morbidities, including hypothyroidism (44%), were prevalent in COVISHIELD-received RA patients. Antibody concentration varied significantly among DMARDs usage groups in COVAXIN-vaccinated RA patients, with a notable difference between three-drug and HCQ-alone regimens. However, no such difference was observed in the COVISHIELD group. Disease duration did not significantly impact antispike antibody concentration in either of the vaccination group. Conclusion: RA patients had a decreased antibody response, 1 year after receiving the second dose of the COVID-19 vaccine. Nonetheless, there was no discernible difference in the antispike antibody concentration between the COVISHIELD and COVAXIN vaccination groups. Additionally, immunosuppressive medications significantly impact serological responses to these vaccines.

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). 
 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. 
 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 < 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)). 
 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.

Assessing disease activity of rheumatoid arthritis patients and drug-utilization patterns of biologic disease-modifying antirheumatic drugs in the Tuscany region, Italy.

Introduction: The disease activity associated with the drug-utilization patterns of biologic Disease Modifying Anti-Rheumatic Drugs (DMARDs) is poorly investigated in real-world studies on rheumatoid arthritis (RA) patients. To investigate the relationship between biologic DMARD initiation/discontinuations in RA patients identified in the healthcare administrative databases of Tuscany and the Disease Activity Score 28 (DAS28) reported in the medical charts. Methods: This retrospective population-based study included RA's first-ever biologic DMARD users of the Pisa University Hospital from 2014 to 2016. Patients were followed up until 31 December 2019. We evaluated the DAS28 recorded before (T0) and after (T1) the biologic DMARD initiation and before (TD0) and after (TD1) discontinuations. Patients were classified as "off-target" (DAS28 > 3.2) or "in-target" (DAS28 ≤ 3.2). We described the disease activity trends at initiation and discontinuation. Results: Ninety-five users were included (73 women, mean age 59.6). Among 70 patients (74%) with at least three DAS28 measures, 28 (40.0%) were off-target at T0 and 38 (54.3%) in-target at T1. Thirty-three (47%) patients had at least one discontinuation, among those with at least three DAS28 assessments. In the disease activity trend, disease stability or improvement was observed in 28 out of 37 (75.7%) patients at initiation and in 24 out of 37 (64.9%) at discontinuation. Discussion: Biologic DMARD discontinuations identified in the healthcare administrative databasese of Tuscany are frequently observed in situations of controlled RA disease. Further studies are warranted to confirm that these events can be used in studies using healthcare administrative databases as proxies of treatment effectiveness.

Risk of incident cardiovascular events with disease-modifying anti-rheumatic drugs among adults with rheumatoid arthritis: a nested case-control study.

This study examined the risk of cardiovascular disease (CVD) associated with the disease-modifying anti-rheumatic drugs (DMARDs) in rheumatoid arthritis (RA). This nested case-control study used the MarketScan database (2012-2014), involving adult RA patients (aged ≥18 years) initiating either a conventional synthetic (cs) DMARD, biologic DMARD, or targeted synthetic (ts) DMARD between January 1, 2013 and December 31, 2014 (cohort entry) and had no CVD history. Cases were individuals with incident CVD identified using diagnosis codes or procedure codes from medical claims. For each case, 10 age- and sex-matched controls were selected using the incident density sampling with replacement. Prescriptions of DMARDs were measured 90 days before the event date. Conditional logistic regression examined the association of risk of CVD with DMARDs in combination treatment or individual use, with reference to methotrexate (MTX) monotherapy, adjusting for baseline confounders. Subgroup analyses were performed separately in DMARD combination therapy users or individual DMARD users, respectively. In total, 270 cases of incident CVD and 2700 controls were included (mean [standard deviation (SD)] age: 54[1]; 75.6% women). The commonly prescribed DMARD therapies were csDMARD monotherapy (n = 795, 27.04%), followed by tumor necrosis factor inhibitors (TNFi) monotherapy (n = 367, 12.48%), and TNFi in combination with MTX (n = 314, 10.68%). Compared with MTX monotherapy, overall use of DMARD agents was not associated with the differential risk of CVD, including various types of DMARD combination regimens. The findings were similar across subgroup analyses. The study found no differential risk of CVD with DMARDs in combination therapy or monotherapy compared to MTX monotherapy in patients with RA. Key Points • This study evaluated the risk of cardiovascular disease (CVD) associated with the disease-modifying anti-rheumatic drugs (DMARDs) in rheumatoid arthritis (RA). • Findings suggest no differential CVD risk with DMARDs in combination with MTX or used individually compared with MTX monotherapy in patients with early RA. • Further efforts should focus on a better understanding of the mechanism of DMARD combination treatments with MTX in modifying CV risk.

New-onset atrial fibrillation in seropositive rheumatoid arthritis: association with disease-modifying anti-rheumatic drugs treatment.

Atrial fibrillation (AF) is a potentially lethal complication that leads to increased hospitalization, disability and mortality. Furthermore, the risk of cardiovascular disease is increased in RA. We evaluated whether DMARD treatment is associated with incident AF in patients with seropositive RA (SPRA). The South Korean Health Insurance Review and Assessment Service database was used to identify patients newly diagnosed with SPRA between 2010 and 2020. A nested case-control analysis was performed to match AF-affected patients to unaffected controls for age, sex, follow-up duration, and index year of SPRA diagnosis at a 1:4 ratio. Adjusted conditional logistic regression was used to identify the predictive factors for AF. Of the 108 085 patients with SPRA, 2,629 (2.4%) developed new-onset AF, and the proportion of females was ∼67%. In the matched population, pre-existing comorbidities of hypertension, chronic kidney disease, and heart failure were associated with increased risk of AF. Meanwhile, the use of methotrexate (MTX) decreased the risk of incident AF [adjusted odds ratio (aOR), 0.89], whereas the use of leflunomide (LEF) increased AF (aOR, 1.21). In a subgroup of patients aged ≥50 years, LEF and adalimumab increased the occurrence of AF, while MTX decreased AF in males and LEF increased this risk in females. Although the number of subjects developing new-onset AF was small, MTX decreased and LEF increased incident AF in patients with RA. Especially, a distinct pattern of AF risk with DMARDs usage was observed according to age and sex.

Disease-Modifying Antirheumatic Drug Use and Its Effect on Long-term Opioid Use in Patients With Rheumatoid Arthritis.

The prevalence of chronic pain is high in patients with rheumatoid arthritis (RA), increasing the risk for opioid use. The objective of this study was to assess disease-modifying antirheumatic drug (DMARD) use and its effect on long-term opioid use in patients with RA. This cohort study included Medicare beneficiaries with diagnosis of RA who received at least 30-day consecutive prescription of opioids in 2017 (n = 23,608). The patients were grouped into non-DMARD and DMARD users, who were further subdivided into regimens set forth by the American College of Rheumatology. The outcome measured was long-term opioid use in 2018 defined as at least 90-day consecutive prescription of opioids. Dose and duration of opioid use were also assessed. A multivariable model identifying factors associated with non-DMARD use was also performed. Compared with non-DMARD users, the odds of long-term opioid use were significantly lower among DMARD users (odds ratio, 0.89; 95% confidence interval, 0.83-0.95). All regimens except non-tumor necrosis factor biologic + methotrexate were associated with lower odds of long-term opioid use relative to non-DMARD users. The mean total morphine milligram equivalent, morphine milligram equivalent per day, and total days of opioid use were lower among DMARD users compared with non-DMARD users. Older age, male sex, Black race, psychiatric and medical comorbidities, and not being seen by a rheumatologist were significantly associated with non-DMARD use. Disease-modifying antirheumatic drug use was associated with lower odds of long-term opioid use among RA patients with baseline opioid prescription. Factors associated with non-DMARD use represent a window of opportunity for intervention to improve pain-related quality of life in patients living with RA.

Trajectories of Adherence to Biologic Disease-Modifying Anti-Rheumatic Drugs in Tuscan Administrative Databases: The Pathfinder Study.

Scanty information on clustering longitudinal real-world data is available in the medical literature about the adherence implementation phase in rheumatoid arthritis (RA). To identify and characterize trajectories by analyzing the implementation phase of adherence to biologic Disease-Modifying Anti-Rheumatic Drugs (DMARDs), we conducted a retrospective cohort drug-utilization study using Tuscan administrative databases. RA patients were identified by a validated algorithm, including the first biologic DMARD supply from 2010 to 2015, RA specialist visit in the year before or after the first supply date and RA diagnosis in the five years before or in the year after the first supply date. We observed users for three years or until death, neoplasia, or pregnancy. We evaluated adherence quarterly through the Medication Possession Ratio. Firstly, we identified adherence trajectories and described the baseline characteristics; then, we focused on the trajectory most populated to distinguish the related sub-trajectories. We identified 952 first ever-biologic DMARD users in RA (712 females, mean age 52.7 years old, standard deviation 18.8). The biologic DMARD mostly supplied was etanercept (387 users) followed by adalimumab (233). Among 935 users with at least 3 adherence values, we identified 49 fully-adherent users, 829 continuous users, and 57 early-discontinuing users. Significant differences were observed among the index drugs. After focusing on the continuous users, three sub-trajectories were identified: continuous-steady users (556), continuous-alternate users (207), and continuous-declining users (66). No relevant differences emerged at the baseline. The majority of first ever-biologic DMARD users showed a continuous adherence behavior in RA. The role of adherence potential predictors and the association with effectiveness and safety outcomes should be explored by further studies.

Increased radiographic progression of distal hand osteoarthritis occurring during biologic DMARD monotherapy for concomitant rheumatoid arthritis

ObjectivesA considerable proportion of patients with rheumatoid arthritis (RA) also suffer from hand osteoarthritis (OA). We here assess the association between conventional synthetic (cs) and biological (b) disease-modifying antirheumatic drugs (DMARDs) and radiographic distal interphalangeal-(DIP) OA in patients with RA.MethodsAdult RA patients from a longitudinal Swiss registry of rheumatic diseases who had ≥ 2 hand radiographs were included at the first radiograph and followed until the outcome or the last radiograph. Patients were grouped into two cohorts based on whether DIP OA was present or absent at cohort entry (cohorts 1 and 2, respectively). Modified Kellgren-Lawrence scores (KLS) were obtained by evaluating DIP joints for the severity of osteophytes, joint space narrowing, subchondral sclerosis, and erosions. KLS ≥ 2 in ≥ 1 DIP joint indicated incident or existing OA, and increase of ≥ 1 in KLS in ≥ 1 DIP joint indicated progression in existing DIP OA. Time-varying Cox regression and generalized estimating equation (GEE) analyses were performed. We estimated hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CI) of DIP OA incidence (cohort 2), or progression (cohort 1), in bDMARD monotherapy, bDMARD/csDMARD combination therapy, and past or never DMARD use, when compared to csDMARD use. In post hoc analyses, we descriptively and analytically assessed the individual KLS features in cohort 1.ResultsAmong 2234 RA patients with 5928 radiographs, 1340 patients had DIP OA at baseline (cohort 1). Radiographic progression of DIP OA was characterized by new or progressive osteophyte formation (666, 52.4%), joint space narrowing (379, 27.5%), subchondral sclerosis (238, 17.8%), or erosions (62, 4.3%). bDMARD monotherapy had an increased risk of radiographic DIP OA progression compared to csDMARD monotherapy (adjusted HR 1.34 [95% CI 1.07–1.69]). The risk was not significant in csDMARD/bDMARD combination users (HR 1.12 [95% CI 0.96–1.31]), absent in past DMARD users (HR 0.96 [95% CI 0.66–1.41]), and significantly lower among never DMARD users (HR 0.54 [95% CI 0.33–0.90]). Osteophyte progression (HR 1.74 [95% CI 1.11–2.74]) was the most significantly increased OA feature with bDMARD use compared to csDMARD use. In 894 patients without initial DIP OA (cohort 2), the risk of incident OA did not differ between the treatment groups. The results from GEE analyses corroborated all findings.ConclusionsThese real-world RA cohort data indicate that monotherapy with bDMARDs is associated with increased radiographic progression of existing DIP OA, but not with incident DIP OA.

Experience of guselkumab usage in the treatment of patients with psoriatic arthritis in real clinical practice

The article presents an analysis of literature on the efficacy and safety of a new biologic disease modifying antirheumatic drug usage, the interleukin 23 inhibitor – guselkumab (GUS) – in the treatment of patients with psoriatic arthritis (PsA). Two own clinical observations of GUS therapy are described. It has been demonstrated that in PsA of moderate activity and in severe to moderate psoriasis with nail damage, the use of GUS (100 mg at weeks 0 and 4, and then every 8 weeks), allows to achieve remission of peripheral arthritis, enthesitis and psoriasis by the 20th week of treatment as in the monotherapy regimen and in combination with methotrexate. When GUS is re-prescribed (re-treat) after a long break (10 months), its effectiveness is quickly and completely restored. The safety of GUS was confirmed in patients with comorbid pathology, in particular, Gilbert's syndrome, hyperuricemia, metabolic disorders (abdominal obesity).

Incidence of inpatient venous thromboembolism in treated patients with rheumatoid arthritis and the association with switching biologic or targeted synthetic disease-modifying antirheumatic drugs (DMARDs) in the real-world setting

ObjectivesTo assess incidence rates (IRs) of VTE in patients with rheumatoid arthritis (RA) on different DMARDs and DMARD switchers.MethodsAdults with RA on a DMARD between 2007 and 2017 were studied...

Depression in rheumatoid arthritis patients: Screening for a frequent yet underestimated comorbidity

Aim of the workTo screen for depression and assess its frequency in rheumatoid arthritis (RA) patients and to study its relation to clinical parameters, patient-reported outcomes (PROs) and disease activity. Patients and methodsThis study included 200 consecutive adult RA patients. Clinical and laboratory investigations were performed. PROs including tender and swollen joint count, patient’s estimated pain, patient global assessment (PGA), validated Arabic version of the health assessment questionnaire (HAQ-A) as well as physician global assessment were considered. The disease activity score (DAS28) and simplified erosion narrowing score (SENS) were calculated. Patient health questionnaire-9 (PHQ-9) was used to detect depression. ResultsThe patients’ mean age was 41.3 ± 11.9 years and disease duration 6.6 ± 4.9 years, 79% were females and 21% males (F:M 3.8:1). Their mean DAS28 was 6 ± 1.7 and HAQ-A 1.9 ± 0.9. The mean PHQ-9 score was 7.6 ± 9.3. 45% of patients had depression; mild (3%), moderate (13%), moderate/severe (13%) and severe (16%) degrees. PHQ-9 significantly correlated with age, disease duration, morning stiffness, joint deformity, C-reactive protein, erythrocyte sedimentation rate and rheumatoid factor and negatively with disease modifying anti-rheumatic drugs usage (p = 0.002). All PROs and DAS28 significantly correlated with PHQ-9 (p < 0.0001). Logistic regression analysis showed that joint surgery (p = 0.004), steroid usage (p = 0.005), functional status (p < 0.0001) and joint damage (p < 0.0001) independently significantly increased the probability of depression occurrence. ConclusionDepression is common among rheumatoid arthritis patients. Periodic routine screening for depression in RA should be included in clinical practice to prevent poor outcomes and to adapt therapies to the specific situation of individual patients.

Can Disease-Modifying Anti-Rheumatic Drugs Reduce the Risk of Developing Dementia in Patients with Rheumatoid Arthritis?

Disease-modifying anti-rheumatic drugs (DMARDs) can reduce inflammation and slow progression of rheumatoid arthritis (RA). It remains unknown what impact DMARDs may have on dementia, where inflammation also plays a critical role in pathogenesis. Patients without a prior history of dementia who were newly diagnosed with RA between 2000 and 2005 were identified from Taiwan's National Health Insurance Research Database. The participants were stratified by age and gender. The outcome of interest was all-cause dementia, and Cox regression models were used to estimate the hazard ratio (HR) of dementia. The cumulative DMARD dosage was stratified by quartiles of defined daily doses. A total of 20,707 patients were diagnosed with RA, and 62,121 non-RA individuals aged 20years or older were included. Cox proportional hazard regression analysis revealed that the RA cohort was 37% less likely to develop dementia compared with the non-RA cohort [adjusted HR 0.63, 95% confidence interval (CI) 0.55-0.72]. Further decreased risk was noted in DMARD users (adjusted HR 0.48, 95% CI 0.39-0.58) with dose-dependent effect. Subgroup analysis identified DMARD use as having a protective effect against developing dementia in female and younger patients. Also, in male and older patients, DMARD use further reduced the risk. These observations suggest that DMARDs may reduce the risk of developing dementia, and its effect is further increased at high cumulative dosages. These findings warrant further examination in randomized control trials.

Biologic Disease-Modifying Antirheumatic Drugs and Risk of Multiple Myeloma

INTRODUCTIONBiologic disease-modifying antirheumatic drugs (DMARDs) are used more frequently and earlier in the course of rheumatologic conditions in a treat-to-target approach. These medications act on proteins and cytokines with potential pro- and anti-malignancy roles, including tumor necrosis factor-alpha (TNF), human interleukin (IL) receptors and B- and T-cell functions. There is concern for hematologic malignancy with some but not all biologic DMARDs. Little is known about possible associations between these medications and development of multiple myeloma (MM). Our purpose was to determine risk of MM in relation to biologic DMARD treatment, duration of use and by biologic target in a large cohort of patients with rheumatologic conditions. METHODSWe conducted a nested case-control study within a cohort of adults undergoing active treatment for rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis. Patients were sampled from a population of commercially-insured U.S. health plan enrollees in the Truven Health MarketScan Research Database between 2009 and 2015. MM cases were ascertained using validated algorithms for administrative data. Up to ten controls from the overall cohort were matched to each MM case on age, sex and rheumatologic indication using incidence density sampling with replacement. Index date was defined as the date of MM diagnosis for a case and corresponding time at-risk for matched controls. Exposure was defined as both treatment and duration of biologic DMARD use including TNF inhibitor (etanercept, infliximab, adalimumab, golimumab, certolizumab pegol), IL-6 receptor antagonist (tocilizumab), T-cell targeted (abatacept) and B-cell depleting (rituximab) agents and were determined from health claims and pharmacy dispensing data. Data on rheumatologic indication, comorbid conditions and treatment with prescription nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids and conventional synthetic DMARDs (hydroxychloroquine, sulfasalazine, methotrexate, leflunomide) were documented in the 12 month baseline period and during follow up as potential confounders. An exposure lag time of 365 days was used to minimize protopathic bias. Multivariable conditional logistic regression models were used to calculate adjusted odds ratios (OR) and 95% confidence intervals (CI) for risk of MM associated with biologic DMARDs. RESULTSFrom a retrospective cohort of 56866 adult patients with rheumatologic conditions, 287 MM cases and 2760 matched controls were identified. Compared to controls, a higher proportion of cases had Charlson comorbidity scores of 2 or greater (24% vs 18%) and used oral corticosteroids during follow up (67% vs 61%). Cases and controls were similar with respect to use of prescription NSAIDs (56% vs 59%) and use of conventional DMARDs (63% vs 67%). Use of biologic DMARDs overall was similar between cases and controls (14% vs 15%), although cases had a slightly lower proportion of etanercept users (5% vs 7%) and a slightly higher proportion of tocilizumab users (1.4% vs 0.4%). Biologic DMARD users were younger, more likely to have psoriatic arthritis or ankylosing spondylitis, lower comorbidity and greater use of concomitant NSAIDs and oral corticosteroids.Risk of MM was neither associated with biologic DMARD use overall (OR 0.84; 95% CI 0.57, 1.26; P=0.40) nor with longer duration of biologic DMARD use (>2.5 years: OR 0.72; 95% CI 0.34, 1.52; P=0.39). However, compared to patients treated with only conventional DMARDs, those receiving concomitant conventional plus biologic DMARDs had a 48% lower risk of developing MM (OR 0.52; 95% CI 0.30, 0.88; P=0.02). Associations with MM appeared to differ by specific biologic DMARD agent with estimates suggesting a lowered risk of MM with use of etanercept (OR 0.55; 95% CI 0.30, 1.02; P=0.06) and greater risk with use of tocilizumab (OR 4.33; 95% CI 1.33, 14.19; P=0.02) that was statistically significant, although confidence intervals were wide. CONCLUSIONSThe potential influence of biologic DMARDs on multiple myeloma is complex. We found that immune suppression with conventional plus biologic DMARDs is inversely associated with MM risk in patients with rheumatologic conditions, but this association differed by biologic drug target. Further research is needed to understand the roles of DMARDs targeting TNF and IL-6 in relation to subsequent myeloma pathogenesis. DisclosuresPatel:Celgene: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Janssen: Honoraria.

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.

An autumn tale: geriatric rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by erosive arthritis and systemic organ involvement. The disease may affect all ages and both sexes; usually it is seen in young women aged 25-45. Recent studies have shown that RA is among the most common inflammatory disease in older age groups. While elderly-onset rheumatoid arthritis (EORA) is still discussed in the literature, it is generally accepted as a disease beginning after 65 years of age. Compared with young-onset rheumatoid arthritis (YORA), it was found that EORA had different characteristics. EORA is characterized by more equal gender distribution, higher frequency of acute onset with constitutional symptoms, more frequent involvement of large joints, and lower frequency of rheumatoid factor (RF) positivity. Earlier diagnosis, less erosive disease and less disease-modifying antirheumatic drug usage were reported as distinguishing EORA from YORA patients. These various clinical presentations may cause difficulties in diagnosis and differential diagnosis of EORA. However, different clinical and treatment approaches may be needed in these patients. In this article, the clinical and laboratory characteristics, prognosis and treatment principles of EORA will be discussed in light of recent literature data.

Undetectable Mannose Binding Lectin and Corticosteroids Increase Serious Infection Risk in Rheumatoid Arthritis

Infection is the leading cause of death in rheumatoid arthritis (RA). Corticosteroid (CS) use is a known and important risk factor for serious infections (SIs). Mannose binding lectin (MBL) is a genetically determined component of the innate immune system implicated in neonatal infections. Our aim was to determine whether MBL deficiency is a risk factor for SIs in RA and to compare it with CS use and also synthetic and biologic disease-modifying antirheumatic drug (DMARD) therapy. Data on 228 patients with RA were collected for up to 7 years (median= 5.9 years). Serum MBL concentrations were determined in all patients receiving synthetic (n= 96) or biologic (n= 132) DMARD therapy. High rates of SIs were observed in RA irrespective of treatment (17%). Similar rates of SIs were observed in synthetic and biologic DMARD users. The rates of single and multiple SIs were similar, irrespective of the use of a biologic agent. Undetectable MBL (<56 ng/mL) concentrations and maintenance prednisolone at 10 mg per day or higher were associated with an increased risk for an SI, with incident risk ratio of 4.67 (P= .001) and 4.70 (P < .001), respectively. Undetectable MBL and prednisolone confer a high risk for an SI. The use of biologic DMARDs did not confer substantial SI risk in this observational study. MBL deficiency is hitherto an unrecognized risk factor for an SI in RA.

Association between use of disease-modifying antirheumatic drugs and diabetes in patients with ankylosing spondylitis, rheumatoid arthritis, or psoriasis/psoriatic arthritis: a nationwide, population-based cohort study of 84,989 patients.

PurposeThe aim of this study is to investigate the association between the use of disease-modifying antirheumatic drugs (DMARDs) and diabetes mellitus (DM) in patients with ankylosing spondylitis (AS), rheumatoid arthritis (RA), or psoriasis/psoriatic arthritis (PS/PSA).Patients and methodsThis retrospective cohort study used a nationwide, population-based administrative database to enroll 84,989 cases with AS, RA, or PS/PSA who initiated treatment with anti-tumor necrosis factor (anti-TNF) drugs or nonbiologic DMARDs. Multivariable analysis was used to estimate the effect of different therapies on the risk of DM.ResultsThe incidence rates of DM per 1,000 person-years were 8.3 for users of anti-TNF drugs, 13.3 for users of cyclosporine (CSA), 8.4 for users of hydroxychloroquine (HCQ), and 8.1 for users of other nonbiologic DMARDs. Compared with the users of nonbiologic DMARDs, the multivariate-adjusted hazard ratios (aHRs) for DM were significantly lower for those who used anti-TNF drugs with HCQ (aHR: 0.49, 95% confidence interval [CI]: 0.36–0.66) and those who used HCQ alone (aHR: 0.70, 95% CI: 0.63–0.78), but not for those who used anti-TNFs without HCQ (aHR: 1.23, 95% CI: 0.94–1.60) or CSA (aHR: 1.14, 95% CI: 0.77–1.70).ConclusionThe aHR for DM was lowest for patients with RA and PS/PSA who initiated treatment with an anti-TNF agent with concomitant HCQ, followed by HCQ users. Those who used anti-TNF agents without HCQ and other nonbiologic DMARDs had a similar risk of DM.

Identifying factors associated with concordance with the American College of Rheumatology rheumatoid arthritis treatment recommendations.

BackgroundFactors associated with care concordant with the American College of Rheumatology (ACR) recommendations for the use of disease-modifying antirheumatic drugs (DMARDs) in rheumatoid arthritis (RA) are unknown.MethodsWe identified a national cohort of biologic-naive patients with RA with visits between December 2008 and February 2013. Treatment acceleration (initiation or dose escalation of biologic and nonbiologic DMARDs) in response to moderate to high disease activity (using the Clinical Disease Activity Index) was assessed. The population was divided into two subcohorts: (1) methotrexate (MTX)-only users and (2) multiple nonbiologic DMARD users. In both subcohorts, we compared the characteristics of patients who received care consistent with the ACR recommendations (e.g., prescriptions for treatment acceleration) and their providers with the characteristics of those who did not at the conclusion of one visit and over two visits, using logistic regression and adjusting for clustering of patients by rheumatologist.ResultsOur study included 741 MTX monotherapy and 995 multiple nonbiologic DMARD users cared for by 139 providers. Only 36.2 % of MTX monotherapy users and 39.6 % of multiple nonbiologic DMARD users received care consistent with the recommendations after one visit, which increased over two visits to 78.3 % and 76.2 %, respectively (25–30 % achieved low disease activity by the second visit without DMARD acceleration). Increasing time since the ACR publication on RA treatment recommendations was not associated with improved adherence.ConclusionsAllowing two encounters for treatment acceleration was associated with an increase in care concordant with the recommendations; however, time since publication was not.

Predictors of treatment initiation with tumor necrosis factor-α inhibitors in patients with rheumatoid arthritis.

Introduction of biologic disease-modifying antirheumatic drugs (DMARDs) has revolutionized treatment in patients with rheumatoid arthritis (RA). However, due to substantially higher costs of biologics compared with nonbiologics, patients with less insurance generosity may have difficulty affording these agents, which may lead to potential access disparities. To identify factors affecting treatment initiation with tumor necrosis factor (TNF)-α inhibitor biologics in patients with RA. Health insurance claims data derived from Truven's MarketScan Commercial Claims and Encounters and Medicare Supplemental and Coordination of Benefits (2007-2010) were used to conduct a retrospective cohort study. Two separate cohorts of RA patients were identified: (1) monotherapy nonbiologic DMARD users and (2) combination therapy nonbiologic DMARD users. The primary outcome was TNF-α inhibitor initiation 12 months following an index inpatient or outpatient RA visit during 2008-2009. Predictors were measured 12 months pre-index and grouped into predisposing, enabling, or need factors based on Andersen's Behavior Model. Predisposing variables included age, sex, and geographic location; enabling variables included insurance-related factors such as capitation, payer type, and insurance generosity, which was defined using cost-sharing information from prescriptions filled by the patients in the previous year; and need variables included disease-related factors such as severity of RA, use of pain control medications, and presence of other comorbidities. Hierarchical logistic regression models were used to derive estimates of the impact of individual predictors. Initiation of TNF-α inhibitors was observed in 10.31% of the monotherapy nonbiologic DMARD users (1,922 of 18,641) and 13.09% of combination nonbiologic DMARD users (983 of 7,508). Among monotherapy nonbiologic DMARD users, initiation with TNF-α inhibitors was associated with the predisposing factors of age (OR = 0.98, 95% CI = 0.97-0.98 for each year increase) and geographic region (Midwest vs. South OR = 0.83, 95% CI = 0.73-0.93; Northeast vs. South OR = 0.77, 95% CI = 0.64-0.92; and West vs. South OR = 0.86, 95% CI = 0.74-0.99); enabling factors of visit to rheumatologists (1 visit vs. no visit OR = 1.22, 95% CI = 1.01-1.46), health insurance type (commercial vs. Medicare supplemental OR = 0.79, 95% CI = 0.66-0.95), and drug benefit generosity (above average vs. poor OR = 1.16, 95% CI = 1.01-1.34 and most generous vs. poor OR = 1.21, 95% CI = 1.05-1.40); and need factors of RA severity (OR = 1.19, 95% CI = 1.14-1.23 for each unit increase in a claims-based RA severity index [CIRAS]), pre-index pain reliever use (steroids OR = 1.81, 95% CI = 1.62-2.02; nonselective nonsteroidal anti-inflammatory drugs [NSAID] OR = 1.17, 95% CI = 1.05-1.31; COX-2 inhibitors OR = 1.22, 95% CI = 1.05-1.41), and comorbidities (OR = 0.94, 95% CI = 0.90-0.99 for each unit increase in a comorbidity index). Treatment initiation with TNF-α inhibitors among patients with combination therapy nonbiologic DMARDs use at baseline was associated with age (OR = 0.98, 95% CI = 0.97-0.99 for each year increase) and region (Midwest vs. South OR = 0.81, 95% CI = 0.68-0.96). Stronger associations with some of the need factors were observed (CIRAS OR = 1.28, 95% CI = 1.21-1.35 for each unit increase, steroids use OR = 2.05, 95% CI = 1.73-2.42, and nonselective NSAID use OR = 1.36, 95% CI = 1.17-1.58) in these patients compared with the monotherapy nonbiologic DMARD users. However, unlike the monotherapy DMARD user group, the enabling factors of health insurance type and drug benefit generosity were not found to be associated with TNF-α inhibitor initiation among nonbiologic DMARD combination therapy users. Potential disparities in the initiation of TNF-α inhibitors among RA patients on monotherapy DMARDs at baseline were noted among older patients, patients in certain geographic region of the United States, and patients with less generous prescription drug benefits. Although future research should examine the impact of these disparities on health outcomes, payers should be aware of the potential for undertreatment among these groups of RA patients when making formulary decisions.

Risk of major cardiovascular events in patients with psoriatic arthritis, psoriasis and rheumatoid arthritis: a population-based cohort study

ObjectivesWe aimed to quantify the risk of major adverse cardiovascular events (MACE) among patients with psoriatic arthritis (PsA), rheumatoid arthritis (RA) and psoriasis without known PsA compared with the general...