Treatment Adherence and Adherence Patterns of Tofacitinib and Self-Injectable TNFi Use in People with Rheumatoid Arthritis.

OBJECTIVE: To assess tofacitinib and self-injectable tumor necrosis factor inhibitor (TNFi) adherence using the Medication Event Monitoring System (MEMS) and characterize association with adherence in patients with rheumatoid arthritis (RA). METHODS: Eligible patients were enrolled from the Forward Databank within 6 months of initiating tofacitinib or injectable TNFi or from participating clinics where these were first prescribed. MEMS caps and patient diaries were used to compile dosing over 9 months. Demographics and disease characteristics were collected every 6 months, and the Beliefs about Medicines Questionnaire only at baseline. Adherence along with its components, initiation, implementation, and persistence, were calculated. RESULTS: Of the 112 consented to participate, 82 (73%) remained in the final analysis with recruitment from clinics 47 (57%) and Forward 35 (43%). Sixty-two (76%) initiated tofacitinib with 87% taking it quaque die and twenty (24%) TNFi. At 9 months, 77% of tofacitinib were persistent versus 70% for TNFi (P = 0.65), and implementation was similar (0.84 vs. 0.82; P = 0.57). In multivariable models, increased baseline patient global assessment was consistently associated with discontinuation (hazard ratio 1.31 [1.07-1.61]). There was increased adherence to methotrexate (MTX) when taking tofacitinib that led to higher combined adherence for tofacitinib than TNFi (0.81 vs. 0.69; P = 0.03), but no significant differences remained in multivariable models. In sensitivity analysis, consistent morning intake for tofacitinib and evening intake for MTX was associated with improved adherence. CONCLUSION: We found no statistical differences in adherence between patients with RA initiating tofacitinib and self-injectable TNFi, although 15% to 30% were nonadherent. Concomitant MTX, patient global assessment, and a consistent time of day intake were associated with adherence.

Smoking cessation patterns, usefulness of quitting methods, and tobacco cessation motivators and barriers to quit in patients with rheumatoid arthritis.

OBJECTIVE: Tobacco use is highly discouraged in patients with rheumatoid arthritis (RA) due to related short and long-term health implications. We aimed to evaluate smoking cessation patterns in patients with RA. In addition, we ascertained perceptions on the usefulness of quitting methods, and perceived motivators and barriers to quit. METHODS: We surveyed adults with RA enrolled in the FORWARD Databank who self-identified as former or current tobacco users. RESULTS: Three hundred forty-eight participants completed the survey and responded to the question "do you currently smoke" (former use = 319; current use = 29). Nicotine replacement therapy (NRT) was perceived as extremely/somewhat useful by 31%, followed by individual 27% and group counseling 21%. Experiencing a major health event was the most common motivator to quit. Current users on average smoked 17 cigarettes per day. Six of the 29 current users had used electronic cigarettes in the past 30 days. The most frequent methods used to quit were "cold turkey quitting," NRT, and prescription medicines. Only 8 of the 23 current users had plans to quit or expressed being ready to make changes to quit. Reasons most frequently listed to not quit were using smoking to manage negative emotions, as a pleasurable habit, to manage other addictions, and to provide a sense of control (e.g., to cope with RA). CONCLUSIONS: Current users expressed several negative emotions including coping with the disease and "being a pleasurable habit" when trying to quit. Future cessation programs should address these barriers to support patients with RA. Key Points • First study characterizing the smoking behavior of patients with RA in the USA. Current users were younger, had a shorter disease duration, and worse disease outcomes compared to former smokers. • Former and current users reported similar motivators to quit, with experiencing a major health event being most common. Only about a third of participants who quit or who were still smoking received advice from a health professional. • The most common reasons for not quitting were that smoking help to manage negative emotions and was a pleasurable habit. Future studies should focus on cessation programs that support participants with RA by addressing the unique perceptions about smoking in this population.

Smartphone-based behavioral monitoring and patient-reported outcomes in adults with rheumatic and musculoskeletal disease.

BACKGROUND: Rheumatic and musculoskeletal diseases (RMD) are associated with depression, fatigue, and disturbed sleep - symptoms that often impact behavior and activity. Patient reported outcomes (PROs) are a way of collecting information on the patient symptom experience directly from the individual. The purpose of this study was to measure and compare user smartphone sensor and activity data in adults with RMDs and assess associations with PROs. METHODS: We invited adults with RMDs enrolled in the FORWARD Databank to participate by installing a custom app on their smartphone and answering PROs (pain, global, HAQ-II) questions daily and weekly over 3 years. Passive data collected included mobility distance, unique calls and text messages, call durations, and number of missed calls. Confounders included sociodemographic, clinical, passive phone behavior, and seasonal factors. Kappa statistics between PRO and flares were computed to measure agreement. The agreement between daily and weekly VAS pain was estimated using the intraclass (ICC) correlation of a two-way random effect model. The relationship between the weekly PRO outcomes and the passive phone data was analyzed with a linear mixed-effect model (LMM), including a random intercept for participant and slope for time in the study with an unstructured covariate structure. RESULTS: Of the 446 participants, the mean (SD) age was 54 (12) years, most (65.5%) had rheumatoid arthritis (RA), the vast majority (91%) were female, and the US Northeast has the least representation (12%). Longer reaction times, interaction diversity, and higher mobility were associated with worse PROs while longer text messages were associated with better PROs. Participants in this study showed good levels of adherence which holds promise for future interventions using passive behavior measures in self-management and clinical follow-up. CONCLUSION: This is the first study to examine passive smartphone behavior with PROs in RMDs and we found significant associations between these behaviors and important health outcomes of pain and function. As smartphone usage continues to change, future studies should validate and expand on our findings with a goal of finding changes in patient symptoms passively through mobile device monitoring.

Risk factors for venous thromboembolism and atherosclerotic cardiovascular disease: do they differ in patients with rheumatoid arthritis?

OBJECTIVE: Venous thromboembolism (VTE) is an increasing concern in rheumatoid arthritis (RA) with little known about risk factors. We aimed to compare risk factors for unprovoked VTE and atherosclerotic cardiovascular disease (ASCVD) in patients with RA and to assess subsequent ASCVD risk after an unprovoked VTE. METHODS: People with RA participating in a US-wide longitudinal observational registry from 1998 to 2018 were assessed for incident unprovoked VTE (deep venous thrombosis and pulmonary emboli not associated with cancer, recent surgery, hospitalisation, fracture and pregnancy) and ASCVD (myocardial infarction and stroke) validated from hospital/death records. Risk factors for VTE and ASCVD and the risk of ASCVD after an unprovoked VTE were determined using Cox proportional hazards models. RESULTS: During median (IQR) 4 (1.5-7) years of follow-up in 31 366 patients with RA, 539 unprovoked VTE and 1648 ASCVD events were identified. The adjusted models showed increased VTE and ASCVD risk with older age, male sex, comorbidities, prior fracture, worse disability, higher disease activity and glucocorticoids. Traditional cardiovascular disease risk factors were common in both ASCVD and VTE but only increased ASCVD risk with obesity as the exception (VTE HR (95% CI), 1.46 (1.13-1.87)) and ASCVD, 0.58 (0.50-0.68)). ASCVD risk doubled after an unprovoked VTE (HR (95% CI), 2.05 (1.43-2.95)). CONCLUSION: Our findings suggest that unprovoked VTE is mediated by inflammation of RA and may be considered a spectrum of pan-cardiovascular syndrome.

Acceptability and Content Validity of Patient-Reported Outcome Measures Considered From the Perspective of Patients With Rheumatoid Arthritis.

OBJECTIVE: To consider the acceptability and content validity of patient-reported outcome measures commonly used in rheumatoid arthritis by describing patients' perceptions of patient-reported outcome measures and comparing patients' responses on patient-reported outcome measures with their verbal accounts of disease impacts. METHODS: We used a sequential mixed methods approach, combining analysis of interviews and data from patient-reported outcome measures (from the Health Assessment Questionnaire, the Functional Assessment of Chronic Illness Therapy-Fatigue subscale, the EuroQol 5-domain instrument, the Short Form 36 health survey, and a visual analog scale [VAS] for pain, fatigue, sleep, and patient global assessment of disease activity). Qualitative analysis of patients' perceptions of patient-reported outcome measures informed a subsequent comparison between data from patient-reported outcome measures and verbal accounts of pain, fatigue, sleep, and functional limitations to assess the effectiveness of patient-reported outcome measures in communicating disease impact. RESULTS: The study included 18 patients. Although a few patients offered positive comments about patient-reported outcome measures, most doubted that patient-reported outcome measures could accurately convey their experience of symptoms and functional limitations. Patients discussed the ease of responding to questions, capturing and conveying symptoms, and concerns about the underreporting of symptoms and interpretation of responses. Compared with verbal accounts, patient-reported outcome measures often did not convey the personal significance of limitations; however, patient-reported outcome measures captured limitations that patients omitted or described with insufficient detail during interviews. Although verbal accounts of pain could be categorized into 3 levels of severity (pain without interference in activities, pain is not the worst ever experienced but interferes with activities, and pain is omnipresent), the pain VAS was more effective at conveying finer gradations in pain severity. CONCLUSION: Although patients may feel that patient-reported outcome measures have certain shortcomings, patient-reported outcome measures also have advantages relative to verbal discussion for communicating symptoms and disease impact.

Real-World Adherence to Oral Methotrexate Measured Electronically in Patients With Established Rheumatoid Arthritis.

OBJECTIVE: To assess methotrexate (MTX) adherence using the Medication Event Monitoring System (MEMS) and characterize associations with adherence in patients with rheumatoid arthritis (RA). METHODS: Eligible patients participated in Forward, the National Databank for Rheumatic Diseases, and recently (12 months or sooner) initiated oral MTX. MEMS was used to compile MTX weekly dosing over 24 weeks. The Beliefs about Medicines Questionnaire (BMQ) was completed, and baseline demographics and disease characteristics obtained. MTX adherence (percentage of weeks dose taken correctly), implementation (percentage of weeks dose taken correctly from initiation until last dose), and persistence (duration from initiation to last dose) were calculated. Analyses measured associations between patient characteristics and adherence, modeled using logistic generalized estimating equations and censored Poisson regression, and persistence modeled using Cox regression. RESULTS: Overall, 60 of 119 eligible patients were included in the analysis. MTX adherence, implementation, and persistence were 75%, 80%, and 83%, respectively, at 24 weeks. Demographics and disease characteristics were generally similar between patients with 1 week or less and 2 weeks or more of missed MTX. Unemployment, less disability, higher Patient Global scores, and no prior disease-modifying antirheumatic drug (DMARD) use were associated with correct dosing. No significant differences in adherence were observed between patients receiving concomitant MTX versus MTX monotherapy, and biologic DMARD-experienced versus biologic DMARD-naïve patients. Higher scores in BMQ Specific Necessity (indicating a greater belief in the necessity of the medication) was associated with a decreased likelihood of dosing at an interval shorter than prescribed (odds ratio 0.89). CONCLUSION: Even in a participatory group over a short period, MTX adherence was suboptimal and associated with certain demographics, medication experience, and beliefs about medicines. This suggests a need for screening and alternative treatment opportunities in nonadherent MTX patients with RA.

Safety of abatacept compared with other biologic and conventional synthetic disease-modifying antirheumatic drugs in patients with rheumatoid arthritis: data from an observational study.

BACKGROUND: To assess the risks of malignancies, infections and autoimmune diseases in patients with rheumatoid arthritis (RA) treated with abatacept compared with other biologic (b) disease-modifying antirheumatic drugs (DMARDs) or conventional synthetic (cs)DMARDs, in a US-wide observational RA cohort METHODS: Data were reviewed from patients (≥ 18 years) with RA who were registered with FORWARD, the National Databank for Rheumatic Diseases, and who initiated abatacept, other bDMARDs or csDMARDs between 2005 and 2015. Patients who switched treatment during the study could be allocated to more than one group. The incidence rates (IRs) by treatment were calculated for malignancies, hospitalized infections and autoimmune diseases identified by six monthly questionnaires and medical records. The hazard ratios (HRs) (95% confidence intervals [CIs]) for all outcomes with abatacept compared with other bDMARDs or csDMARDs were determined using marginal structural models adjusted for clinical confounders. RESULTS: In the study sample, 1496 initiated abatacept, 3490 initiated another bDMARD and 1520 initiated a csDMARD. The risk of malignancies with abatacept was not statistically significant versus other bDMARDs (HR [95% CI)] 1.89 [0.93, 3.84]) or versus csDMARDs (HR [95% CI] 0.93 [0.20, 4.27]). Patients receiving abatacept versus other bDMARDs were at a lower risk of hospitalized infections (HR [95% CI] 0.37 [0.18, 0.75]); the risk versus csDMARDs was lower with wide CIs (HR [95% CI] 0.31 [0.09, 1.05]). The relative risks for psoriasis were similar between treatment groups (HR [95% CI] 1.46 [0.76, 2.81] and HR [95% CI] 2.05 [0.59, 7.16] for abatacept versus other bDMARDs and versus csDMARDS, respectively). The IR (95% CI) of severe infusion/injection reactions was lower with abatacept compared with other bDMARDs (1.57 [1.11, 2.17] vs 2.31 [1.87, 2.82] per 100 patient-years, respectively). CONCLUSIONS: In this analysis, abatacept was well tolerated and did not result in an overall increased risk of malignancies, infections or autoimmune diseases compared with other bDMARDs or csDMARDs.

The impact of menopause on functional status in women with rheumatoid arthritis.

Objective: The aim of this study was to investigate the association of menopause with functional status outcomes in women with RA. Methods: Participants were women in a US-wide observational cohort who developed RA before menopause. The HAQ measured functional status. We controlled for confounding variables and used univariate and multivariable generalized estimating equation methods with the sandwich estimator of variance. Best models were selected using the quasi-likelihood under the independence model criterion. A sensitivity analysis was performed using linear mixed effects regression models. Results: A total of 8189 women were eligible. Of these, 2005 (24.5%) were pre-menopausal, 611 (7.5%) transitioned through menopause during the study, and 5573 (68.1%) were post-menopausal. Within each respective group, the mean (s.d.) ages were 39.7 (7.8), 50.7 (3.4) and 62.3 (9.3) years. Our results showed that women who were pre-menopausal had less functional decline as measured by the HAQ compared with women who were post-menopausal; these results were robust and strong even after adjustment for other significant factors. The ever-use of hormonal replacement therapy, ever having a pregnancy, and longer length of reproductive life were associated with less functional decline. After menopause, the trajectory of functional decline worsened and accelerated in women with RA. Conclusion: The results suggest that menopausal status is associated with functional decline in women with RA. Furthermore, menopause is associated with a worsening progression of functional decline. These data indicate that menopause has a significant impact on the level and rate of functional decline in women with RA.

New method to characterize microbial diversity using flow cytometry.

The majority of microorganisms have yet to be cultivated and represent a vast uncharacterized and untapped resource. Here, we report the utilization of a combination of flow cytometry, cultivation, and molecular genetics to develop new methodologies to access and characterize biodiversity in microbial samples. We demonstrate that fluorescent dyes and combinations of dyes can selectively stain portions of bacterial populations that can be isolated as sub-populations using fluorescence-activated cell sorting (FACS). Microbial sub-populations obtained by FACS differ substantially from the original microbial population, as demonstrated by denaturing gradient gel electrophoresis and determination of 16S rRNA gene sequences. These sub-populations can subsequently be used to inoculate microbial growth media, allowing the isolation of different microbial species from those that can be readily cultivated from the original sample using the same microbial growth media. When this technique was applied to the analysis of activated-sludge and Yellowstone Lake hydrothermal vent samples, comparative analysis of 16S rDNA sequences revealed that FACS allowed the detection of numerous bacterial species, including previously unknown species, not readily detectable in the original sample due to low relative abundance. This approach may result in a convenient methodology to more thoroughly characterize microbial biodiversity.