Arthritis Medication Research Articles

EP16 The impact of comorbidities on individuals with inflammatory arthritis

Abstract Background Inflammatory arthritis (IA) predisposes to comorbidities (CC) including cardiovascular disease, osteoporosis, depression, infections, and cancer. CC are associated with higher mortality, poorer quality of life, and greater utilisation of health resources. Treating CC can be challenging and their impact is not addressed by current guidelines. The patient’s perspective of living with multiple conditions remains largely unexplored. We explored patient experience, impact of CC and polypharmacy on their quality of life and activities of daily living. Methods A mixed methods approach has been used. Patients with a definite diagnosis of IA with at least 1 Charlson comorbidity were invited to answer questionnaires. A sample of patients was invited for an in-depth qualitative interview which was analysed using thematic analysis approach. Results 146 patients from 3 centres were recruited. 82 (56%) were females. 58 (40%) had 1 CC, 62 (42.5%) had ≥2 CC, 21 (14.5%) had ≥4 CC. Most common CC was hypertension 76 (53%), pulmonary disease 49 (34%), and diabetes 34 (23.5%). 28 (19%) remained in full time employment and 19 (13%) were unemployed. 27 (18.5%) had to cut down hours because of illness. Disease duration was >10 years in 74 (51%), 5-10 years in 29 (20%), 3- 5 yrs in 21 (14%) and <3 years in 22 (15%). Self-rated severity of disease was rated as low (26%), moderate (42%), severe (24%) and very severe (5.5%). Awareness and impact of CC: 77 (53%) expressed that CC affected their health as much as their arthritis. No information on CC was provided in 27 (18%), minimal information in 35 (24%) and detailed information 69 (47%). 68 (47%) were aware that some of the comorbidities could be the result of the disease or medications and 72 (49%) weren’t aware. 82 (56%) needed help from their family members/carers and of those 30% needed help daily due to CC. Polypharmacy: 73 (50%) stated either they were not involved or ‘just a little’ in choice of medication. 23 (15%) needed medication for side effects. 116 (79%) stated that doctors discuss the risks and benefits at follow ups. 130 (89%) take arthritis and CC related medication regularly. Lifestyle advice: 106 (73%) stated that education on CC wasn’t offered. 24 (16%) were not offered smoking cessation and 32 (22%) declined smoking cessation clinics. 43 (30%) weren’t aware that obesity could cause joint pains or increase the risk of diabetes, hypertension or IHD. 95 (65%) said advice on benefits of exercise was provided. Light exercises such as walking for minimum of 30 minutes was undertaken by 75%: reasons for not exercising were pain, fatigue, lack of motivation, low morale and CC. Conclusion This novel study provides insight into patient experiences of understanding comorbidities in the context of inflammatory arthritis. CC have a large impact on their lives and current care does not adequately meet their needs with respect to education of CC, understanding the impact, shared decision-making and lifestyle advice. Disclosures G.M. Koduri Honoraria; Roche. Grants/research support; Funding from Charity. N. Gullick None. F. Hayes None. A. Kayani None. S. Dubey None. C. Mukhtyar None.

P17 Prediction of response of methotrexate in patients with rheumatoid arthritis using serum lipidomics

Abstract Background For patients with rheumatoid arthritis (RA), introduction of early, effective therapy has consistently been shown to improve long-term outcomes. Low-dose methotrexate (MTX) is commonly prescribed as first-line treatment for RA. However, MTX is not effective for a large minority of patients and there is currently no way to determine ahead of therapy which patients are most likely to benefit. Metabolomics and lipidomics are emerging approaches for studying patient stratification in RA and have the potential to identify disease processes that underpin treatment outcomes. Here we apply state-of-the-art machine learning algorithms to predict MTX treatment response, by testing serum lipid levels measured at two time-points (pre-treatment and following 4 weeks on drug) to predict MTX response by 6 months. Methods This study included patients from the Rheumatoid Arthritis Medication Study (RAMS), a UK multi-centre one-year prospective observational study investigating predictors of response to MTX in patients with RA. Since 2008, patients who are about to start MTX for the first time are asked to provide demographic and clinical data, as well as blood samples to permit DNA, RNA and serum-based biomarker studies. Patients about to commence MTX treatment were followed longitudinally and those categorised as good or non-responders following 6 months on-drug using EULAR response criteria were analysed. Serum lipid levels were measured at pre-treatment and following 4 weeks on drug using ultra-performance liquid chromatography tailored for complex lipid analysis, coupled to mass spectrometry. State-of-the-art supervised machine learning methods were then applied to predict EULAR response at 6 months. Models including lipid levels were compared to models including clinical covariates (including: MTX start dose, steroid use at inclusion, BMI, number of swollen joints, number of tender joints, CRP levels, patients’ assessment of their overall wellbeing, gender, age-at-inclusion, age-at-onset, disease duration, HAQ score and pre-treatment smoking habits). Results Following quality control, 3,366 features (1,060 in negatively-charged mode and 2,306 in positive mode) were available for analysis at pre-treatment and 4 weeks from 100 RA patients categorised as good (GR, n = 50) or poor (NR, n = 50) responders to MTX following 6 months on drug. The best model performance for the classifier including clinical covariates was observed using L1/L2-regularised logistic regression (ROC AUC 0.68 ± 0.02). However, the clinical covariate model outperformed the classifier including lipid levels when either pre- or on-treatment time-points were investigated (ROC AUC 0.61 ± 0.02). Conclusion These data do not support the utility of early treatment lipidomic monitoring in routine clinical practice in patients started on MTX for their RA. Disclosures M. Maciejewski: Shareholder/stock ownership; owns stock or stock options in Pfizer. C. Sands None. N. Nair None. S. Ling None. S. Verstappen None. K. Hyrich None. A. Barton None. D. Ziemek Shareholder/stock ownership; owns stock or stock options in Pfizer. M. Lewis None. D. Plant None.

EP14 Association between initial csDMARD strategy and disease activity at 6 months in patients with new onset rheumatoid arthritis

Abstract Background Until 2018, NICE guidance recommended the use of a combination of disease-modifying anti-rheumatic drugs (DMARDs), including methotrexate (MTX), in the initial management of people with rheumatoid arthritis (RA). In 2018 the guideline was updated to recommend monotherapy with MTX due to uncertainties in the evidence for combination therapy. However, it remains a requirement for progression onto any biologic that the patient should have persistent high disease activity and/or have intolerance to, a minimum of two DMARDs. The aim of this study was to understand the association between initial treatment strategy and EULAR response at 6 months. Methods This analysis included patients recruited to the longitudinal observational Rheumatoid Arthritis Medication Study (RAMS) in the UK who were DMARD naïve and had symptoms for less than 1 year. Patients were defined as either starting MTX monotherapy or MTX in combination with another DMARD (6 weeks either side of MTX start date) and categorised into EULAR non responders or moderate/ good responders after 6 months. A logistic regression model was applied to test the association between initial treatment strategy and EULAR response at 6 months, adjusting for confounders. Results A total of 948 participants were included in the analysis. MTX monotherapy was prescribed in 72% (n = 678) of patients and combination therapy was prescribed in 28% (n = 270) of patients, the majority of whom received MTX plus hydroxychloroquine (HCQ) (n = 236, 87%). There was no significant difference between the MTX monotherapy and combination therapy groups in EULAR response at 6-months (adjusted odds ratio [aOR] 0.77, 95% CI 0.53 to 1.14). Conclusion In this large UK observational study investigating the effect of treatment strategy within the first 6 weeks of presentation and treatment response at 6 months, there was no significant difference between combination DMARD therapy and MTX monotherapy on EULAR response. Most patients received MTX in combination with HCQ, for which little evidence exists. Disclosures S. Wood None. K. Hyrich Consultancies; ABBVIE. Grants/research support; BMS, PFIZER, UCB. S. Verstappen None. D. Steinke None.

The Management of Perioperative Immunosuppressant Medications for Rheumatoid Arthritis During Elective Hand Surgery

Rheumatoid arthritis (RA) is a destructive inflammatory disease that commonly involves joints of the hand and wrist. Different recommendations exist for continuing or discontinuing immunosuppressant medications during the perioperative time period. The purpose of our study was to determine whether continuing or discontinuing medications (steroids, nonbiological, and/or biological disease-modifying antirheumatic drugs [DMARDs]) were associated with an increased or decreased risk of postoperative complications. We performed a single-center, retrospective review of a cohort of RA patients who had elective hand surgery by a single surgeon. Patients were included if they had a documented diagnosis of seropositive RA by a rheumatologist and had elective hand surgery and/or a disease-related surgical procedure involving the upper extremity between January 2008 and August 2018. We stratified patients into different groups for comparison by classes of immunosuppressant medications for managing RA. These classes included corticosteroids, nonbiological DMARDs, biological DMARDs, and/or no medications. Immunosuppressant medications were then compared with no medications for the incidence of postoperative overall complications. Eighty-eight patients had elective hand and/or upper extremity surgeries for RA. Mean patient age at the time of surgery (± SD) was 55 ± 13 years (range, 24-74 years). Of these 88 patients, 8 (9%) overall complications occurred. Complications were wound healing failures (n= 5), tendon rupture (n= 1), hematoma (n= 1), and surgical-site infection (n= 1). Perioperative medications included steroids (n= 31), nonbiological DMARDs (n= 68), biological DMARDs (n= 5), and no medication (n= 27). There were no significant differences in overall complications between patients on immunosuppressant medications and those on no medications. Median (interquartile range) follow-up was 11.5 months (5-25.8) (range, 2-74 months). We found that patients who continued or discontinued medications within 1 dosing interval of their usual dose perioperatively had similar rates of complications following elective hand surgery. Therapeutic IV.

Predictors of presenteeism, absenteeism and job loss in patients commencing methotrexate or biologic therapy for rheumatoid arthritis.

ObjectivesWork is an important health outcome. This study aimed to identify predictors of work loss, absenteeism and presenteeism over 1 year in RA patients commencing treatment with MTX or biologics.MethodsPatients aged 18–65 years in full/part-time employment from two UK prospective cohorts were included: MTX-starters = Rheumatoid Arthritis Medication Study; and biologic-starters = Biologics in Rheumatoid Arthritis Genetics and Genomics Study Syndicate. Presenteeism and absenteeism were assessed using the RA-specific Work Productivity Survey at baseline, and 6 and 12 months. Potential predictors including baseline age, gender, clinical measures (e.g. disability, pain, fatigue), psychological distress, occupation and EULAR response from baseline to 6 months were investigated.ResultsA total of 51/463 MTX-starters and 30/260 biologic-starters left work over 12 months. Higher baseline psychological distress in MTX-starters [odds ratio (OR) 1.1 (95% CI: 1.0, 1.1)] and higher disability in biologic-starters [OR 3.5 (95% CI: 1.4, 8.6)] predicted work loss. Some 16.1% of patients reported sick-leave, which was predicted by disability [OR (95% CI): MTX-starters: 1.5 (0.9, 2.3); biologic-starters: 2.4 (1.1, 5.2)]. Median presenteeism scores were very low (minimal interference) in both cohorts. Higher fatigue for MTX starters [incidence rate ratio 1.2 (95% CI: 1.0, 1.4)] and higher disability in biologic-starters (incidence rate ratio 1.4 (95% CI: 1.1, 1.7)] predicted presenteeism. Good EULAR response was associated with lower absenteeism and presenteeism in both cohorts.ConclusionPatients with RA still face significant limitations regarding their ability to work. Disability and EULAR response were the main predictors of work outcomes, emphasizing the need to control the disease and the importance of function in enabling work participation.

Risk management model in patients receiving therapy with biotechnological medications for rheumatoid arthritis in a medical center in Barranquilla, Colombia

Risk management model in patients receiving therapy with biotechnological medications for rheumatoid arthritis in a medical center in Barranquilla, Colombia

Long-term outcomes of patients who rate symptoms of rheumatoid arthritis as 'satisfactory'.

ObjectivesTo describe outcomes of patients with early RA in a patient acceptable symptom state (PASS) at treatment initiation and to identify clusters of symptoms associated with poor outcomes.MethodsData came from the Rheumatoid Arthritis Medication Study, a UK multicentre cohort study of RA patients starting MTX. The HAQ, DAS28 and other patient-reported outcome measures (PROMs) were collected at baseline, and at 6 and 12 months. Patients answering yes to the question ‘Is your current condition satisfactory, when you take your general functioning and your current pain into consideration?’ were defined as PASS; patients answering no were defined as N-PASS. Symptom clusters in the baseline PASS group were identified using K-medians cluster analysis. Outcomes of baseline PASS vs N-PASS patients and each cluster are compared using random effects models.ResultsOf 1127 patients, 572 (50.8%) reported being in PASS at baseline. Over one year, baseline PASS patients had lower DAS28 (mean difference = −0.71, 95% CI −0.83, −0.59) and HAQ scores (mean difference = −0.48, 95% CI −0.56, −0.41) compared with N-PASS patients. Within the baseline PASS group, we identified six symptom clusters. Clusters characterized by high disease activity and high PROMs, or moderate disease activity and high PROMs, had the worst outcomes compared with the other clusters.ConclusionDespite reporting their condition as ‘satisfactory’, early RA patients with high PROM scores are less likely to respond to therapy. This group may require increased vigilance to optimize outcomes.

Access to high-cost medications for psoriatic arthritis in the National Health System in Brazil: the long path up to dispensation

BackgroundPharmaceutical Assistance (PA) is a dynamic and multidisciplinary process that aims to supply health systems, programs or services with quality medicines, enabling access and health care, in an efficient and timely manner. The objective of the study was to evaluate the profile of administrative processes for the treatment of PsA, identify the time elapsed in the flow of processes and its associated factors.MethodsA cross-sectional study of medication requests for the treatment of PsA was carried out between November 2014 and December 2016. Linear regression was used to verify the factors associated with time to delivery.ResultsA total of 218 cases containing 250 drugs were analyzed. The median time between the medical appointment and the first dispensation was 66 days (interquartile range, 44–90). The State proceedings, which includes requesting the drug until the authorization of treatment, was the stage that most contributed to the total time spent. The factors associated with the longer time to delivery of medications were prescriptions coming from clinics and specialty centers, from dermatologists, non-authorized processes and non-persistent patients in the treatment in 12 months.ConclusionThe median time to receive medicines for the PsA treatment in Belo Horizonte health region after a medical prescription was higher than 2 months. The time between the solicitation of the medicines and the authorization of the treatment in the SUS (State administrative procedure) was the main component of the total time spent.

Patterns of polypharmacy before diagnosis of dementia: a data-driven, retrospective, population-based study with primary care electronic health records

BackgroundPolypharmacy presents a serious and significant public health challenge as average lifespans increase. The objective of this study was to identify patterns of polypharmacy before dementia diagnosis, their prevalence, and possible complications. MethodsWe used electronic health records in the Welsh general practitioners’ database from 1990 to 2015, via the Secure Anonymised Information Linkage Databank. Cohort selection, based on a previously validated phenotype, was done with the use of Read Codes to identify any dementia diagnosis within the dataset. No age restriction was applied, but complete data for each patient was required. Analysis was stratified by sex and age, but not dementia type. Medications were identified by Read Codes, and split into four 5-year sub-periods. Factor analysis was used for patients taking at least three medicines in each period. FindingsWe identified 33 451 patients with a dementia diagnosis from more than 42 million rows of health records. 22 011 (65·8%) patients in the cohort were female, with mean age at dementia diagnosis of 72·75 years (SD 13·59). In sub-period 1 (0–5 years pre-diagnosis), 22 157 (82·2%) of 26 968 patients were taking three or more medications, and three clusters were identified: medicines for urinary or respiratory infections, arthritis or rheumatism, and heart disease (17 947 [66·5%] patients); medicines for urinary or respiratory infections, arthritis or rheumatism, heart disease, and depression (5938 [22·0%]); and medicines for osteoarthritis (701 [2·6%]). By contrast, in sub-period 4 (15–20 years pre-diagnosis), 421 (5·5%) of 7660 patients were taking three or more medications, and five patterns emerged: medicines for infections, arthropathy, and cardiovascular disease (421 [5·5%] patients); medicines for anxiety and acute respiratory infection (184 [2·4%]); medicines for acute respiratory infection and cardiovascular disease (161 [2·1%]); medicines for dermatological disease (23 [0·3%]); and medicines for asthma and other acute respiratory infections (four [0·1%]). 23 891 (71·4%) patients in all periods took medications for arthritis, heart disease, and infections, with or without medications for mental health. InterpretationThe earlier before dementia diagnosis, the greater the number of medicine clusters are observed, with lower prevalence of each cluster. Understanding how dementia medicines interact and cause complications with other groups of medicines is fundamental. These patterns can inform safe prescribing practices before diagnosis in selecting medicines with a low anticholinergic burden to minimise their effect on cognitive impairments. Further analysis of these types of polypharmacy among people without dementia will be done in the future. FundingHealth Data Research UK (NIWA1).

Toward Accelerated Authorization and Access to New Medicines for Juvenile Idiopathic Arthritis.

A meeting was organized to bring together multiple stakeholders involved in the testing and authorization of new medications for juvenile idiopathic arthritis (JIA) to discuss current issues surrounding clinical trials and access to new medications for children and adolescents with JIA. The Childhood Arthritis and Rheumatology Research Alliance invited representatives of regulatory agencies (Food and Drug Administration and European Medicines Agency), and major pharmaceutical companies with JIA-approved products or products in development, patient and parent representatives, representatives of an advocacy organization (Arthritis Foundation), and pediatric rheumatology clinicians/investigators to a 1-day meeting in April 2018. The participants engaged in discussion regarding issues in clinical trials. As the pharmacologic options to treat inflammatory arthritis rapidly expand, registration trial designs to test medications in JIA patients must adapt. Many methodologies successfully used in the recent past are no longer feasible. The pool of patients meeting entry criteria who are willing to participate is shrinking while the number of medications to be tested is growing. Suggested solutions included proposing innovative clinical trial methods to regulatory agencies, as well as open discussions among stakeholders. Ensuring that new medications are authorized in a timely manner to meet the needs of JIA patients worldwide is critical. Approaches should include open dialog between regulatory agencies, pharmaceutical companies, and other stakeholders to develop and implement novel study designs, including patient and clinician perspectives to define meaningful trial outcomes, and changing existing study plans.

Differential DNA methylation correlates with response to methotrexate in rheumatoid arthritis.

ObjectivesIdentifying blood-based biomarkers that predict treatment response in RA is a clinical priority. We investigated differential DNA methylation as a candidate biomarker of response for the first-line drug used in RA, MTX.MethodsDNA methylation was measured in DNA samples from individuals recruited to the Rheumatoid Arthritis Medication Study. Differentially methylated positions were compared between whole blood samples collected at baseline and at 4 weeks from patients who, by 6 months, had a good (n = 34) or poor response (n = 34) to MTX using linear modelling, adjusting for gender, age, cell composition, baseline 28-joint disease activity score (DAS28) and smoking status. Analyses also compared methylation with changes in DAS28 and changes in swollen joint count and tender joint count, and changes in CRP over the initial 6 months after MTX commencement. Differentially methylated positions showing significant differences with any response parameter were tested using pyrosequencing in an independent group of 100 patients from the Rheumatoid Arthritis Medication Study.ResultsIn the discovery group, two CpG sites showed methylation changes at 4 weeks associated with clinical EULAR response by 6 months. Significant changes in methylation for three differentially methylated positions associated with change in tender joint counts, three with change in swollen joint count and a further four with change in CRP. Of the 12 CpGs, four showed replicated association in an independent dataset of samples from the Rheumatoid Arthritis Medication Study.ConclusionThese data represent an advance on current practice by contributing to a personalized medicine strategy allowing an escalation or change in therapy as early as 4 weeks.

Impact of a specialty pharmacy benefit on rheumatoid arthritis medication adherence and functional status: a continuation study

Background: Patients with rheumatoid arthritis (RA) have benefited from the introduction of tumor necrosis factor (TNF) inhibitors; however, multiple studies have reported that rates of medication adherence are sub-optimal. Specialty pharmacies offer various management strategies to improve adherence in patients with RA to help improve disease status. Aims: To expand the initial analysis results by gathering adherence data between 6 and 12 months and HAQ-II scores at 12 months after transitioning members to the specialty pharmacy to determine the impact of a specialty pharmacy benefit on RA medication adherence and functional status. Methods: A retrospective analysis was conducted using an internal pharmacoadherence application. Members with claims for TNF-inhibitors were included, provided they received at least two fills within the study time periods of May 1, 2017–December 31, 2017 (pre-transition), January 1, 2018–August 31, 2018 (post-transition), and September 1, 2018–April 30, 2019 (extension). Pharmacy claims were analyzed to measure adherence by calculating the proportion of days covered (PDC) in each time period. Members with a baseline HAQ-II score after transition were compared to 6-month post-transition and 12-month extension HAQ-II scores for a correlation to adherence. Results: A total of 101 members with RA were included. Prior to transition, 34% of members were filling at non-specialty pharmacies and 66% of members were filling at specialty pharmacies. PDC values for baseline, post-transition, and extension time periods were 0.848, 0.907, and 0.819, respectively, for members filling at non-specialty pharmacies prior to transition and 0.904, 0.889, and 0.818, respectively, for members filling at a specialty pharmacy prior to transition. The percentage of patients achieving a desired adherence level (PDC>0.8) increased post-transition for members previously filling at non-specialty pharmacies (65.2% vs 84.8%). A statistically significant inverse relationship was found between baseline HAQ-II score and pre-transition PDC value (r = –0.200, p = .035) for 112 members with completed functional assessments. Conclusions: PDC is significantly correlated to HAQ-II scores at baseline, and adherence is also shown to increase for members transitioning from a non-specialty to specialty pharmacy. More analysis is needed to determine if the HAQ-II is an appropriate functionality questionnaire to assess RA disease status.

KIDNEY DAMAGE IN PATIENTS WITH RHEUMATOID ARTHRITIS

The purpose of this work is to perform a general analysis of relevant literature on the issue of kidney damage in patients with rheumatoid arthritis. Kidney damage in patients with rheumatic diseases is potentially dangerous, as it can lead to the development of terminal renal failure that may require replacement renal therapy. Amyloidosis often leads to kidney failure in patients with rheumatoid arthritis. Renal amyloidosis more often develops in patients with acute course of rheumatoid arthritis and under maximal immunological disorders. In patients with renal amyloidosis against the background of rheumatoid arthritis, manifestations of joint affection decrease, while the renal-uremic syndrome takes a predominant role. Signs of nephrotic syndrome and chronic renal failure develop gradually. Kidney damage can be caused by medications for rheumatoid arthritis. The choice of the optimal scheme of individual-centred therapy is vitally important for patients, since every aggravation of both rheumatic disease and secondary renal damage leads to the progression of chronic renal failure.

The predictors of and reasons for non-adherence in an observational cohort of patients with rheumatoid arthritis commencing methotrexate.

In order to develop interventions to optimize MTX use for the treatment of RA we evaluated the rate of, reasons for and predictors of MTX non-adherence during the first 6 months of therapy. The Rheumatoid Arthritis Medication Study (RAMS) is a prospective multicentre cohort study of incident MTX users in the UK. Prior to MTX commencement demographic, clinical and psychological data were collected. A weekly patient-completed diary recorded MTX dose, possible side effects and adherence over 26 weeks. The number of non-adherent weeks was calculated. Potential baseline predictors of ever non-adherence (⩾1 week non-adherent) during the first 6 months of MTX therapy were identified using logistic regression analyses. 606 patients with RA were included; 69% female, mean (s.d.) age 60 (13) years and DAS28 score 4.2 (1.2). Over the first 6 months following MTX initiation, 158 (26%) patients were ever non-adherent (71% intentional, 19% non-intentional, 10% unexplained) and mean (s.d.) number of non-adherent weeks was 2.5 (2.1). Multivariable predictors of ever non-adherence included DAS28 [odds ratios (OR) 1.1, 95% CI 1.0, 1.4], fatigue (OR 1.1, 95% CI 1.0, 1.2 per cm), ⩾2 comorbidities vs no comorbidities (OR 1.9, 95% CI 1.1, 3.5) and high medication concerns despite perceived need (OR 1.1, 95% CI 1.0, 1.1 per unit decrease in need/concern differential). This is the largest study evaluating early intentional and non-intentional non-adherence to MTX, which has identified that patient beliefs and multi-morbidity strongly link with non-adherence. These findings can direct the design of and provide potential targets for interventions to improve patient adherence.

Collection of antirheumatic medication data from both patients and rheumatologists shows strong agreement in a real-world clinical cohort: the Ontario Best Practices Research Initiative—a rheumatoid arthritis cohort

ObjectivesThe objective of the study was to examine the agreement between patient- and rheumatologist-reported antirheumatic medication (ARM) use in the Ontario Best Practices Research Initiative. Study Design and SettingWe included adult patients who enrolled on or after September 1st 2010 and compared ARM use where rheumatologist visits and interviews occurred within 60 days of each other. Kappa statistic was used to measure agreement. We calculated sensitivity, specificity, and positive and negative predictive value, considering patient-reported data as the gold standard. To examine factors associated with agreement, a hierarchical generalized linear model was used. A subset analysis was also completed to compare start and stop dates of ARM. ResultsOverall agreement for ARM was good with higher sensitivity and lower specificity for conventional synthetic disease-modifying antirheumatic drugs compared with biologic disease-modifying antirheumatic drugs. Increased Health Assessment Questionnaire pain index and 28 disease activity score–erythrocyte sedimentation rate (DAS28-ESR) were significantly associated with lower agreement. Reporting stop dates was higher (19.4%) for patient-reported data compared with rheumatologist-reported data (13.1%). ConclusionARM reports had strong agreement particularly for patients who have low disease activity and pain. ARM discontinuation was reported more frequently by patients, which may indicate that patients may be discontinuing use of their rheumatoid arthritis medications before consulting their rheumatologist.

Reduced IgG titers against pertussis in rheumatoid arthritis: Evidence for a citrulline-biased immune response and medication effects

BackgroundThe antibody response to pertussis vaccination in rheumatoid arthritis is unknown, a concerning omission given the relatively low efficacy of the pertussis vaccine, a rise in pertussis infections, and a general increased susceptibility to infection in rheumatoid arthritis. Additionally, the contributions from an intrinsically dysregulated immune system in rheumatoid arthritis and immune-suppressing medications to the response to pertussis vaccination is poorly defined. This study examines antibody titers against pertussis in vaccinated rheumatoid arthritis patients and controls as well as evaluates potential contributions from demographic factors, immune suppressing medications, and reactivity against citrullinated pertussis.MethodsSerum IgG titers against native and citrullinated pertussis and tetanus were quantified by enzyme-linked immunosorbent assay in rheumatoid arthritis subjects and controls who were vaccinated within 10 years. Titers were compared by t-test and percent immunity by Fisher’s exact test. Multivariable logistic regression was used to identify clinical factors that correlate with native pertussis titers.ResultsCompared to controls, rheumatoid arthritis subjects had lower titers against pertussis, but not tetanus, and reduced immunity to pertussis. These results were even more prominent at 5–10 years post-vaccination, when rheumatoid arthritis patients had 50% lower titers than controls and 2.5x more rheumatoid arthritis subjects were not considered immune to pertussis. Multiple logistic regression demonstrated that female sex and methotrexate use, but not TNF inhibiting medications, correlated with reduced immunity to pertussis. Finally, rheumatoid arthritis patients had higher IgG titers against citrullinated pertussis than native pertussis.ConclusionsPertussis titers are lower in vaccinated rheumatoid arthritis patients with evidence for contributions from female sex, a citrulline-biased immune response, and methotrexate use.

Arthritis and diabetes

Arthritis and diabetes

Medication adherence and cost-related medication non-adherence in patients with rheumatoid arthritis: A cross-sectional study.

First, to assess the clinical characteristics and medication adherence to oral rheumatoid arthritis (RA) medications in patients with RA. Second, to examine adherence determinants with a focus on the effect of medication out-of-pocket (OOP) costs on medication adherence to oral RA medications. Lastly, to examine cost-related medication non-adherence (CRN) in patients with RA. A cross-sectional study of patients with RA was conducted at rheumatology outpatient clinics in Shiraz, Iran. The data collection survey consisted of 5 sections including demographic questions, disease-related questions, Compliance Questionnaire Rheumatology (CQR), CRN questions and an open-ended question. SPSS version 24 was used for analysis. A total of 308 completed surveys were collected. Adherence to oral RA medications was 40.3%. Just under 20% of participants were biologic disease-modifying antirheumatic drugs (bDMARDs) users and these bDMARDs users were 0.82 times less likely to be adherent to their oral RA medications compared to non-bDMARDs users (P<0.05). There was no statistically significant association between OOP costs and adherence to oral RA medications (P>0.05). However, 28.7% of participants reported not refilling, delaying to refill, skipping doses or taking smaller doses due to cost. In findings of the open-ended question, medication costs and affordability were the most commonly mentioned barriers to medication adherence. Non-adherence to oral RA medications was prevalent among Iranian patients with RA and OOP costs were a barrier to medication adherence.

Profiling of Gene Expression Biomarkers as a Classifier of Methotrexate Nonresponse in Patients With Rheumatoid Arthritis.

ObjectiveApproximately 30–40% of rheumatoid arthritis (RA) patients who are initially started on low‐dose methotrexate (MTX) will not benefit from the treatment. To date, no reliable biomarkers of MTX inefficacy in RA have been identified. The aim of this study was to analyze whole blood samples from RA patients at 2 time points (pretreatment and 4 weeks following initiation of MTX), to identify gene expression biomarkers of the MTX response.MethodsRA patients who were about to commence treatment with MTX were selected from the Rheumatoid Arthritis Medication Study. Using European League Against Rheumatism (EULAR) response criteria, 42 patients were categorized as good responders and 43 as nonresponders at 6 months following the initation of MTX treatment. Data on whole blood transcript expression were generated, and supervised machine learning methods were used to predict a EULAR nonresponse. Models in which transcript levels were included were compared to models in which clinical covariates alone (e.g., baseline disease activity, sex) were included. Gene network and ontology analysis was also performed.ResultsBased on the ratio of transcript values (i.e., the difference in log2‐transformed expression values between 4 weeks of treatment and pretreatment), a highly predictive classifier of MTX nonresponse was developed using L2‐regularized logistic regression (mean ± SEM area under the receiver operating characteristic [ROC] curve [AUC] 0.78 ± 0.11). This classifier was superior to models that included clinical covariates (ROC AUC 0.63 ± 0.06). Pathway analysis of gene networks revealed significant overrepresentation of type I interferon signaling pathway genes in nonresponders at pretreatment (P = 2.8 × 10−25) and at 4 weeks after treatment initiation (P = 4.9 × 10−28).ConclusionTesting for changes in gene expression between pretreatment and 4 weeks post–treatment initiation may provide an early classifier of the MTX treatment response in RA patients who are unlikely to benefit from MTX over 6 months. Such patients should, therefore, have their treatment escalated more rapidly, which would thus potentially impact treatment pathways. These findings emphasize the importance of a role for early treatment biomarker monitoring in RA patients started on MTX.

Pregnancy outcomes, fertility, and family planning in women with psoriatic arthritis.

To quantify pregnancy outcomes and the frequency and cause of infertility among women with psoriatic arthritis. Women with psoriatic arthritis aged 20-50 years completed a questionnaire about prior pregnancies, infertility, and family planning. Patient-reported pregnancy outcomes were validated by chart review. In 40 women with psoriatic arthritis, 67% of 70 pregnancies were live births. Patient-reported preterm birth and preeclampsia were more common after psoriatic arthritis diagnosis but were significantly over-reported. Most women reported no or mild joint pain during pregnancy and few took medications for psoriatic arthritis. Infertility was reported by 36% of women who were ever pregnant or ever tried to become pregnant, primarily due to polycystic ovary syndrome. The patient-reported pregnancy outcomes in this retrospective survey were not supported by chart review, making prospective studies essential to understand the interaction of psoriatic arthritis and pregnancy. Infertility, particularly due to polycystic ovary syndrome, appears to be an important issue in this population.