Virginia Pascual-Ramos

Inadequate Therapy Behavior Is Associated to Disease Flares in Patients With Rheumatoid Arthritis Who Have Achieved Remission With Disease-Modifying Antirheumatic Drugs

Objectives:(1) To determine 6-month follow-up adherence and persistence with disease-modifying antirheumatic drugs in patients with early rheumatoid arthritis with disease under control. (2) To compare disease flares across adherent, nonadherent, persistent and nonpersistent patients. (3) To identify differences in adherent and persistent rates among therapeutic regimens. (4) To identify baseline prognosticators of poor compliance. Methods:Ninety-three patients (86% female) had 4 consecutive 2-month apart evaluations during which the 28-joint disease activity score and the Health Assessment Questionnaire were scored, comorbidities and treatment recorded and a compliance questionnaire and a drug record registry applied. Descriptive statistics, Student t and &khgr;2 tests and logistic regression analysis were used. Results:At the study entry, patients had mean ± standard deviation age of 40.8 ± 13.9 years, the 28-joint disease activity score of 2.1 ± 1.1, the Health Assessment Questionnaire of 0.09 ± 0.2, and 68 of them (73.1%) had remission. During follow-up, 47 patients (50.5%) were adherent and 51 (54.8%) persistent; 14 of 68 patients (20.6%) who achieved remission had a disease flare. Incidence rate and individual risk of a disease flare were significantly greater in nonadherent and nonpersistent patients. Compared with methotrexate monotherapy, therapeutic regimens with >3 disease-modifying antirheumatic drugs had increased risk of nonadherence and nonpersistence (P ≤ 0.02). Higher previous serial erythrocyte sedimentation rate was associated to nonadherence (as was a shorter follow-up at the Clinic) and to nonpersistence (odds ratio: 1.03; 95% confidence interval: 1.01–1.05 for both, P = 0.05 and P = 0.001, respectively). Conclusions:Therapy behavior of patients with rheumatoid arthritis with mild/no disease activity and disability was poor and translated into disease flares. Higher serologic activity was associated to poor compliance with therapy.

Medication persistence over 2 years of follow-up in a cohort of early rheumatoid arthritis patients: associated factors and relationship with disease activity and with disability

IntroductionAggressive treatment with disease-modifying antirheumatic drugs (DMARDs) plays a major role in improving early rheumatoid arthritis (RA) patient outcomes. Persistence and adherence with medication occurs variably (20% to 70%). The objectives of the study were to determine medication persistence (MP) in early RA patients over 13 consecutive visits each 2 months apart, to investigate the relationship between MP and disease activity, disability and structural damage, and to identify baseline prognosticators.MethodsCharts from 75 patients of an early RA cohort were reviewed. At each visit, a rheumatologist interviewed patients regarding therapy, scored disease activity with the 28-joint disease activity score (DAS28) and disability with the health assessment questionnaire (HAQ), and recorded comorbidities and treatment. A complete medical history was obtained at baseline. MP was defined as the duration of time from initiation to discontinuation of at least one DMARD and/or corticosteroids for at least 1 week and was reported as a dichotomous variable at consecutive evaluations. Structural damage was defined by detection of new erosions on radiography. Descriptive statistics, Students t test, the chi-squared test, and logistic regression analyses were used.ResultsThe proportion of MP patients decreased from 98% at 2 months to 34% at 2 years. MP patients (n = 32) had similar DAS28 to non-MP patients (n = 53) at initial visits, lower DAS28 and greater DAS28 improvements at follow-ups (P ≤ 0.05 at visits 4, 6, 7 and 9) and reached sustained remission (≥ 3 consecutive visits with DAS28 < 2.6) more frequently (82.8% versus 46.5%, P = 0.003) and earlier (7.7 ± 4.6 versus 13.6 ± 5.7 months, P = 0.001) than non-MP patients. MP patients had similar baseline HAQ scores, but lower HAQ scores at follow-up (P ≤ 0.05 at visits 3, 5, 6, 7, 9, 10 and 13). More non-MP patients developed erosive disease than MP patients (26.8% versus 17.9%, P = 0.56). Older age at baseline was associated with therapy discontinuation (odds ratio = 1.1, 95% confidence interval = 1.007 to 1.103, P = 0.02).ConclusionsDiscontinuation of DMARDs was frequent and progressive in an early RA cohort. Patients with persistence on therapy were younger, had lower disease activity and disability during follow-up, and reached sustained remission more frequently and earlier than patients without it. MP should intentionally be evaluated during follow-up of early RA patients, as it seems to play a major role in outcome.

Hypervascular synovitis and American College of Rheumatology Classification Criteria as predictors of radiographic damage in early rheumatoid arthritis.

To investigate if serial clinical and ultrasound evaluations differ between early rheumatoid arthritis patients who do or do not develop erosive disease and to identify predictors of erosions. Methods: Patients with at least 7 consecutive 2-monthly clinical and 3 consecutive 6-monthly ultrasound evaluations were included. Ultrasound (gray scale and power Doppler) assessed synovitis, power Doppler-positive synovitis (PD+) and power Doppler-negative synovitis (PD−) in each of 14 joints of the dominant hand. After 1 and 2 years, erosive disease was defined according to digitized radiography. Areas under the curve (AUCs) for serial assessments were calculated. Multivariate logistic regression analysis was performed. Results: Seventy-one and 38 patients completed 1- and 2-year consecutive assessments. After 2 years (21.5 ± 6.2 months), 13 patients developed erosions. At baseline, nonerosive patients had shorter duration of symptoms to RA diagnosis, lower number of the American College of Rheumatology (ACR) classification criteria, lesser synovitis and PD+ synovitis than erosive patients. At follow-up, erosive and nonerosive patients showed similar AUC for clinical, serological, and treatment parameters; erosive patients had higher AUCs for synovitis and PD+ synovitis than nonerosive patients. In the multivariate model, the amount of PD+ synovitis (odds ratio, 1.3; 95% confidence interval, 1.11-1.51; P = 0.001) and more ACR classification criteria (odds ratio, 2.3; 95% confidence interval, 1.05-5.02; P = 0.04), both at baseline, predicted erosive disease. Conclusions: Serial Power Doppler ultrasonography-assessed synovitis was greater in patients who developed erosions than in those who did not. More power Doppler positive (hypervascular) synovitis and more ACR classification criteria, both at baseline, were the only predictors of erosions.

Radiographic outcome in Hispanic early rheumatoid arthritis patients treated with conventional disease modifying anti-rheumatic drugs.

OBJECTIVES To determine rates of incident erosive disease in early rheumatoid arthritis patients, to identify baseline predictors and to evaluate erosions impact on patient-reported outcomes. METHODS 82 patients with ≤ 12 months of disease duration, ≥ 3 years of follow-up and conventional treatment were included. Consecutive evaluations assessed swollen and tender joint counts, treatment and comorbidity, acute reactant-phase determinations and patient-reported outcomes. Digitized radiographs of the hands and feet were obtained at baseline and yearly thereafter. RA was defined as erosive when at least one unequivocal cortical bone defect was detected. Descriptive statistics and Cox regression analysis were performed. RESULTS At baseline, 71 of the patients were ♀, population median (range) age was of 38.7 (16-78.2) years, 58 patients had antibodies and all the patients had active disease and substantial disability. Follow-up cohort was of 299.3 person-years. At last follow-up (49 ± 13.8 months), 28 patients developed erosions. Erosions location was the feet, in 12 patients. Incident rates of erosive disease at one, two, three and four years were of 8.1, 12.8, 13.8 and 5.6 per 100 person-years, respectively. Higher C-reactive protein (HR: 1.20, 95%CI: 1.04-1.4, p=0.01) and positive antibodies (HR: 5.09, 95%CI: 1.08-23.86, p=0.04) were baseline predictors of incident erosive disease. Erosions had minor impact on patient-reported outcomes. CONCLUSION Rheumatoid arthritis patients with antibodies and higher C reactive protein at baseline are at risk for incident erosions which appear most frequently at the feet. Up to 1/3 patients conventionally treated develop incident erosions, which minimally impact function.

Educational website incorporating rheumatoid arthritis patient needs for Latin American and Caribbean countries

Health education is fundamental in the management of RA patients. This study explored patient needs for educational material appropriate for RA patients in our region through a website. This study includes seven focus groups and semi-structured interviews across 4 countries (Argentina, Chile, Colombia, and Mexico) with 71 RA patients. Transcripts were analyzed by anthropologists using qualitative analysis (QA), resulting in themes and subthemes to be developed. Five themes and over 50 subthemes of interest were identified by patients. Grouped into categories as follows: (1) knowing the disease, (2) living with arthritis, (3) treatment and therapies for RA, (4) psychosocial support, and (5) information for families. A response was written by the team in plain Spanish on patient subthemes of interest including additional areas that the team considered relevant. Three videos for YouTube were produced: on patient-doctor relationships, patients at work, and home and at the clinic. Illustrations in a comic book format on RA diagnosis were created. The educational site on RA of PANLAR can be found at htpp://artritisreumatoide.cl. This project accomplished a comprehensive list of RA patient interests, revealing the complex relationship between the information on the disease, the experience of a chronic disease, and the way in which patients approach, conceive, and manage their disease. We expect to gather information on how the website will be used in the future for patients and their families and maintain and improve the website as well as adapt its content to different socioeconomic realities.

Predictors of health care drop-out in an inception cohort of patients with early onset rheumatoid arthritis

BackgroundRA patients who eventually dropped out of treatment and out of the health care system had potentially disastrous consequences for their health-related quality-of-life outcomes. Objectives of the study were to identify predictors of health care drop out (HDO) in an inception and ongoing cohort of patients with recent onset RA.MethodsCharts from patients attending an early arthritis clinic from February 2004 to December 2015, and standardized follow-up evaluations were reviewed. Patients with HDO (cases) were defined when they did not return back to the clinic for a schedule visit for at least one year. Persistence with therapy was defined as length of time patients complied with RA-treatment. A case-control nested within a cohort design was used to compare baseline and cumulative (up to HDO or equivalent follow-up) variables between cases and paired controls (patients compliant with scheduled visits). Cox regression analysis was used to investigate predictors of HDO. The study was approved by the Institutional Review Board and patients gave written informed consent to have their data published.ResultsData from 170 patients (89.4% female, [mean±SD] age: 38.2±12.6 years) with ≥1 year of follow-up were analyzed; up to December 2015, (median, interquartile rage) follow-up was 86.6 months (43.2–123) during which 35 (20.6%) patients had HDO after 41.1 months (12.1–58.7). Baseline and cumulative variables related to disease activity, treatment and persistence with therapy entered regression models; cumulative number of flares, number of disease-modifying anti-rheumatic drugs /patient and persistence <50% emerged as predictors of HDO. Five cases returned back after (median, range) drop out time of 3.8 years (2.3–5.8); they exhibited higher disability and poorer function than paired controls and outcomes were sustained up to their last follow-up.ConclusionsIn a real clinical setting of an EAC, failure to control disease activity, intensive treatment and poor persistence with therapy predicted HDO. Abandonment of health care had a negative impact on patient outcomes and was sustained even after health care was reinitiated.

Rheumatoid Arthritis Disease Activity Is Determinant for ABCB1 and ABCG2 Drug-Efflux Transporters Function.

Objective To compare drug efflux function of ABCB1 and ABCG2 transporters in rheumatoid arthritis (RA) patients with active disease and in remission. Methods Twenty two active RA patients (DAS28 ≥3.2) and 22 patients in remission (DAS28<2.6) were selected from an early RA clinic. All patients were evaluated at study inclusion and six months later. ABCB1 and ABCG2 functional activity was measured in peripheral lymphocytes by flow cytometry. The percentage of cells able to extrude substrates for ABCB1 and ABCG2 was recorded. Results Active patients had higher ABCB1 and ABCG2 activity compared with patients in remission (median [interquartile range]): 3.9% (1.4–22.2) vs (1.3% (0.6–3.2), p = 0.003 and 3.9% (1.1–13.3) vs 0.9% (0.5–1.9) p = 0.006 respectively. Both transporters correlated with disease activity assessed by DAS28, rho = 0.45, p = 0.002 and rho = 0.47, p = 0.001 respectively. Correlation was observed between the time from the beginning of treatment and transporter activity: rho = 0.34, p = 0.025 for ABCB1 and rho = 0.35, p = 0.018 for ABCG2. The linear regression model showed that DAS28 and the time from the onset of treatment are predictors of ABCB1 and ABCG2 functional activity, even after adjustment for treatment. After six months we calculated the correlation between change in DAS28 and change in the functional activity in both transporters and found a moderate and significant correlation for ABCG2 (rho = 0.28, p = 0.04) and a non-significant correlation for ABCB1 (rho = 0.22, p = 0.11). Conclusions Patients with active RA have an increased function of ABCB1 and ABCG2, and disease activity is the main determinant of this phenomena.

Tofacitinib, an oral Janus kinase inhibitor, in patients from Mexico with rheumatoid arthritis: Pooled efficacy and safety analyses from Phase 3 and LTE studies

OBJECTIVES Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). We characterized efficacy and safety of tofacitinib in Mexican patients from RA Phase 3 and long-term extension (LTE) studies. METHODS Data from Mexican patients with RA and an inadequate response to disease-modifying antirheumatic drugs (DMARDs) were taken from four Phase 3 studies (pooled across studies) and one open-label LTE study of tofacitinib. Patients received tofacitinib 5 or 10mg twice daily, adalimumab (one Phase 3 study) or placebo (four Phase 3 studies) as monotherapy or in combination with conventional synthetic DMARDs. Efficacy up to Month 12 (Phase 3) and Month 36 (LTE) was assessed by American College of Rheumatology 20/50/70 response rates, Disease Activity Score (erythrocyte sedimentation rate), and Health Assessment Questionnaire-Disability Index. Safety, including incidence rates (IRs; patients with events/100 patient-years) for adverse events (AEs) of special interest, was assessed throughout the studies. RESULTS 119 and 212 Mexican patients were included in the Phase 3 and LTE analyses, respectively. Tofacitinib-treated patients in Phase 3 had numerically greater improvements in efficacy responses versus placebo at Month 3. Efficacy was sustained in Phase 3 and LTE studies. IRs for AEs of special interest were similar to those with tofacitinib in the global and Latin American RA populations. CONCLUSIONS In Mexican patients from the tofacitinib global RA program, tofacitinib efficacy was demonstrated up to Month 12 in Phase 3 studies and Month 36 in the LTE study, with a safety profile consistent with tofacitinib global population.

Las habilidades de comunicación de los aspirantes a la certificación en Reumatología se asocian con su desempeño en el examen clínico objetivo estructurado

BACKGROUND The Mexican Accreditation Council for Rheumatology annually certifies trainees in Rheumatology using a multiple-choice test and an objective structured clinical examination (OSCE). Since 2015, candidates communication skills (CS) have been rated by both patients and by physician examiners and correlated with results on the OSCE. This study compared the CS from candidates to annual accreditation in Rheumatology as rated by patients and by physician examiners, and assessed whether these correlated with candidates performance in the OSCE. MATERIAL AND METHODS From 2015 to 2017, 8areas of CS were evaluated using a Likert scale, in each OSCE station that involved a patient. Both patient and physician evaluators were trained annually and their evaluations were performed blindly. The associations were calculated using the Pearson correlation coefficient. RESULTS In general, candidates were given high CS scores; the scores from patients of the candidates CS were better than those of physician examiners; within the majority of the stations, both scores were found to correlate moderately. In addition, the scoring of CS correlated with trainee performance at the corresponding OSCE station. Interestingly, better correlations were found when the skills were rated by the patients compared to physician scores. The average CS score was correlated with the overall OSCE performance for each trainee, but not with the multiple-choice test, except in the 2017 accreditation process, when a weak correlation was found. CONCLUSIONS CS assessed during a national accreditation process correlated with the candidates performance at the station level and with the overall OSCE.

Patient motivation for non-persistence with medication impacts self-reported compliance

1.1 IntroductionIn 2004 we initiated an inception cohort of patients with recent-onset rheumatoid arthritis (RA). From 2008 onward, compliance (C) was assessed at fixed intervals, using a questionnaire (CQ) that additionally investigated 15 predefined motivations for non-persistence with therapy (P), and a visual analogue scale (C-VAS, 0-100mm). Objectives were to examine the correlation between the CQ and the C-VAS and to investigate if the selection of patient-independent motivations for non-P predicted better self-reported C.1.2 Materials and methodsUp to January 2016, the cohort comprised 180 patients with variable follow-up. Each pre-specified motivation for non-P was classified as patient-dependent or patient-independent by 50 patients randomly selected (≥70% agreement). Descriptive statistics and multiple regression analysis were used. Written informed consent was obtained.1.3 ResultsLength of follow-up from 160 patients for which data were completed and analyzed was 6.7±3.4 years; all the patients scored 1516 pairs of CQ and C-VAS. C-VAS significantly correlated with the CQ, r=0.468, p=0.001. Optimal C-VAS cut-off value to predict CQ-compliance was ≤7.5 mm.During follow-up, there were 670 CQ scored as with non-P among whom, 654 had at least one motivation for non-P selected; of them, 549 CQ (70.2%) corresponded to non-P patients who selected only patient-independent motivations. The selection of exclusively independent motivations for non-P predicted C-VAS and CQ scores. Also, the selection of exclusively independent motivations for non-P predicted compliance either per VAS (OR: 15.6, 95%CI: 5.4-45.3, p≤0.001) or per CQ (OR: 2.25, 95%CI: 1.062-4.664, p=0.034).1.4 Conclusions Patient motivation for non-persistence with medication impacts self-reported C.