A. Pasma

Factors associated with adherence to pharmaceutical treatment for rheumatoid arthritis patients: A systematic review

OBJECTIVES To identify factors associated with adherence to medication for rheumatoid arthritis or undifferentiated inflammatory arthritis using a systematic literature search. METHODS PubMed, PsycINFO, EMbase and CINAHL databases were systematically searched from inception to February 2011. Articles were included if they addressed medication adherence, used a reproducible definition, determinants and its statistical relationship. Methodological quality was assessed using a quality assessment list for observational studies derived from recommendations from Sanderson et al. (2007) [12]. Resulting factors were interpreted using the Health Belief Model (HBM). RESULTS 18 out of 1479 identified studies fulfilled the inclusion criteria. 64 factors were identified and grouped according to the HBM into demographic and psychosocial characteristics, cues to action and perceived benefits versus perceived barriers. The belief that the medication is necessary and DMARD use prior to the use of anti-TNF had strong evidence for a positive association with adherence. There is limited evidence for positive associations between adherence and race other than White, general cognition, satisfactory contact with the healthcare provider and the provision of adequate information from the healthcare provider. There is limited evidence for negative associations between adherence and having HMO insurance, weekly costs of TNF-I, having a busy lifestyle, receiving contradictory information or delivery of information in an insensitive manner by the rheumatologist. 18 factors were unrelated to adherence. CONCLUSIONS The strongest relation with adherence is found to be prior use of DMARDs before using anti-TNF and beliefs about the necessity of the medication. Because the last one is modifiable, this provides hope to improve adherence.

Facilitators and Barriers to Adherence in the Initiation Phase of Disease-modifying Antirheumatic Drug (DMARD) Use in Patients with Arthritis Who Recently Started Their First DMARD Treatment

Objective. To explore themes associated with adherence in the initiation phase for first-time use of disease-modifying antirheumatic drugs (DMARD) in patients with inflammatory arthritis using focus groups and individual interviews. Methods. Thirty-three patients were interviewed in focus groups and individual interviews. Interviews were transcribed verbatim and imported into ATLAS.ti software (Scientific Software Development GmbH). Responses that included reasons for adherence or nonadherence in the initiation phase were extracted and coded by 2 coders separately. The 2 coders conferred until consensus on the codes was achieved. Codes were classified into overarching themes. Results. Five themes emerged: (1) symptom severity, (2) experiences with medication, (3) perceptions about medication and the illness, (4) information about medication, and (5) communication style and trust in the rheumatologist. Conclusion. Perceptions about medication and the communication style with, and trust in, the rheumatologist were mentioned the most in relation to starting DMARD. The rheumatologist plays a crucial role in influencing adherence behavior by addressing perceptions about medication, providing information, and establishing trust in the treatment plan.

Does non-adherence to DMARDs influence hospital-related healthcare costs for early arthritis in the first year of treatment?

Introduction Non-adherence to disease-modifying antirheumatic drugs (DMARDs) is suspected to relate to health care costs. In this study we investigated this relation in the first year of treatment. Methods In a multi-center cohort study with a one year follow up, non-adherence was continuously measured using electronic monitored medication jars. Non-adherence was defined as the number of days with a negative difference between expected and observed opening of the container. Cost measurement focused on hospital costs in the first year: consultations, emergency room visits, hospitalization, medical procedures, imaging modalities, medication costs, and laboratory tests. Cost volumes were registered from patient medical files. We applied multivariate regression analyses for the association between non-adherence and costs, and other variables (age, sex, center, baseline disease activity, diagnosis, socioeconomic status, anxiety and depression) and costs. Results Of the 275 invited patients, 206 were willing to participate. 74.2% had rheumatoid arthritis, 20.9% had psoriatic arthritis and 4.9% undifferentiated arthritis. 23.7% of the patients were more than 20% non-adherent over the follow-up period. Mean costs are € 2117.25 (SD € 3020.32). Non-adherence was positively related to costs in addition to baseline anxiety. Conclusion Non-adherence is associated with health care costs in the first year of treatment for arthritis. This suggests that improving adherence is not only associated with better outcome, but also with savings.

Nonadherence to disease modifying antirheumatic drugs in the first year after diagnosis: comparing three adherence measures in early arthritis patients

OBJECTIVES The aim of this study was to compare three measurement methods for non-adherence to DMARDs in early arthritis patients: the Compliance Questionnaire Rheumatology (CQR), the intracellular uptake of MTX in the form of MTX-polyglutamates (MTX-PGs) and electronic measurement with Medication Event Monitoring Systems (MEMS). METHODS DMARD naïve early arthritis patients were included in an ongoing cohort study. MEMS were used to measure adherence continuously, while every 3 months MTX-PGs were collected together with the CQR. The associations between the measures were estimated with Spearman rank correlations. Sensitivity and specificity of the CQR against a MEMS cut-off was compared at 3, 6, 9 and 12 months. The same applied to MTX-PGs against a MEMS cut-off and MTX-PGs against a CQR cut-off. For the association between MEMS, the CQR and MTX-PGs, a multilevel linear regression model was performed with age, gender, weeks of treatment and MTX dosage as covariates. RESULTS We included 206 patients. Non-adherence measured with MEMS varied over time and between DMARDs. The CQR score was not associated with MEMS non-adherence at 3, 9 and 12 months. At 9 months, MTX-PGs was associated with MEMS non-adherence, as well as with the CQR. All correlations were below 0.30. CONCLUSION Associations between the three measures are weak. Explanations are individual differences in the uptake of MTX, and little variance in adherence between patients. Moreover, the measurement domains differ: perceptions (CQR), behaviour (MEMS) and pharmacokinetics (MTX).

How to study determinants related to medication adherence in newly diagnosed polyarthritis patients for the development of a prediction instrument

Introduction For patients with a chronic disease, the appropriate use of medication is the key to manage their illness. Adherence to medication is therefore important. Adherence can be divided into three parts: the initiation part, the execution phase, and the discontinuation part. Little is known about the determinants of the initiation part. For this reason, we describe the conduct of a stepwise procedure to study determinants of medication initiation for patients with a chronic disease. Methods/design The stepwise procedure comprises of eliciting a list of all potential determinants via literature review, interviewing patients, and consulting an expert panel. This is followed by embedding the determinants in a theoretical framework, developing a questionnaire, and choosing adherence measurement methods. The consecutive steps that we conducted for the development of a tool for the prediction of adherence in our study sample of early arthritis patients are described. Discussion Although we used a thorough procedure, there are still some pitfalls to take into account, such as the choice of theoretical framework. A strength of this study is that we use multiple adherence measurement methods and that we also take clinical outcomes into account.

Psychosocial predictors of DMARD adherence in the first three months of treatment for early arthritis

OBJECTIVES To induce disease remission, early arthritis patients should adhere to their disease-modifying antirheumatic drugs (DMARD) in the first months after diagnosis. It remains unknown why some patients are non-adherent. We aimed to identify patients at risk for non-adherence in the first 3 months of treatment. METHODS Adult DMARD-naive early arthritis patients starting synthetic DMARDs filled out items on potential adherence predictors at baseline. Adherence was measured continuously. Non-adherence was defined as not opening the electronically monitored pill bottle when it should have been. Items were reduced and clustered using principal component analysis. The most discriminating items were identified with latent trait models. We used a multivariable logistic regression model to find non-adherence predictors. RESULTS 301 patients agreed to participate. Adherence was high and declined over time. Principal component analysis led to 7 dimensions, while subsequent latent trait models analyses led to 15 dimensions. Two dimensions were associated with adherence, one dimension was associated with non-adherence. CONCLUSIONS Information seeking behavior and positive expectations about the course of the disease are associated with adherence. Patients who become passive because of pain are at risk for non-adherence. PRACTICE IMPLICATIONS Rheumatologists have cues to identify non-adherence, and may intervene on non-adherence through implementing shared decision making techniques.

Focus group interviews reveal reasons for differences in the perception of disease activity in rheumatoid arthritis

ObjectiveDoctors frequently see patients who have difficulties coping with their disease and rate their disease activity high, despite the fact that according to the doctors, the disease activity is low. This study explored the patients’ perspectives on this discordance that may help to understand why for some patients, usual care seems to be insufficient.MethodsIn our qualitative study we conducted focus group interviews where questions were used as a guideline. Transcripts were analyzed using inductive thematic analysis.FindingsTwenty-nine patients participated in four focus groups. Participants could not put their finger exactly on why doctors estimated that their disease activity was low, while they experienced high levels of disease activity. During the in-depth focus interviews, seven themes emerged that appeared related to high experienced disease activity: (1) perceived stress, (2) balancing activities and rest, (3) medication intake, (4) social stress, (5) relationship with professionals, (6) comorbidity, and (7) physical fitness.ConclusionWhen patients were asked why their view of their disease activity was different from that of their physician, seven themes emerged. The way participants coped with these themes seemed to be the predominant concept. Specific interventions that focus on one or more of the reported themes and on coping may improve not only the quality of life of these patients but also the satisfaction with the patient–doctor relationship for both parties.

THU0083 Non-Adherence to Dmards will Significantly Influence the First-Year Outcome of Rheumatoid Arthritis

Background The initial treatment of rheumatoid arthritis (RA) consists of pharmacological therapy with one or more conventional DMARDs. The treatment target is to obtain early low disease activity, resulting in better radiological and functional outcomes. Non-adherence to DMARDs interferes with reaching this target. The consequences of non-adherence will not only affect the individual patient, but also increase health care costs. Objectives This study investigates if, and to what extent non-adherence to DMARD therapy in RA patients would lead to higher DAS28 scores in the first year of treatment. Methods DMARD naïve patients with rheumatoid arthritis (RA) were consecutively recruited for a cohort study on DMARD adherence in 11 participating hospitals. Patients were selected if they fulfilled the ACR2010 criteria for RA, were above 18 years old and were prescribed DMARDs. Clinical variables were assessed at baseline and every 3 months. Non-adherence was continuously measured using electronically monitored medication containers. Non-adherence was defined as the number of days when the observed amount of openings of the container was lower than the amount of days with expected openings. We calculated the non-adherence proportion in the previous 3 months before DAS28 measurement. The influence of non-adherence on DAS28 after 3, 6, 9 and 12 months after diagnosis was univariately and multivariately tested with 4 generalized linear mixed models using backward elimination. Covariates that were taken into account in the model were age, sex, baseline DAS28, RF positivity, ACPA positivity, anxiety, depression, weeks on DMARD therapy, number of DMARDs at the particular time point, use of subcutaneous methotrexate and use of biologicals. Results 275 patients with inflammatory arthritis were invited to participate, of whom 203 were willing to participate. Of these patients 120 fulfilled the ACR2010 score for RA, which were used for this analysis. During the study, 17 patients became lost to follow up. Non-adherence percentages differed per DMARD. For sulfasalazine, non-adherence was highest (20.9%). For methotrexate, the mean percentage was 13.4%, as for hydroxychloroquine, the percentage was 14%. Overall, there was a decline in adherence over time, except for prednisone (mean 8.5%). The mean baseline DAS28 was 4.7 (SD 1.3), which decreased to 3 (SD 1.3)at 3 months, 2.7 (SD 1.4) at 6 months, 2.5 (SD 1.2) at 9 months and 2.5 (SD1.3) at 12 months. In all models, except for the 12-month model, non-adherence has a significant influence on DAS28, next to weeks on DMARDs, and baseline DAS28 (see figure 1). Conclusions In the first year after diagnosis, it is important to quickly achieve low disease activity or remission, in order to avoid irreversible damage. Non-adherence relates to disease outcome, and thus to irreversible damage. Therefore, interventions towards enhancing adherence can improve disease outcome. Disclosure of Interest None declared

AB1106 First-Year Health Care Costs for Early Arthritis in Daily Practice Related to Medication Non-Adherence and Other Determinants

Background Reviews have shown that 49% to 99% of the patients with rheumatoid arthritis (RA) are adherent to their medication, depending on the measurement method. Non-adherence is associated with worse clinical outcome, more work disability and more health care costs. Up till now, the actual impact of non-adherence to DMARDs on hospital related health care costs has not been investigated. Objectives The aim of this study is 1) to examine the direct hospital-related health care costs for inflammatory arthritis in the first year after diagnosis and 2) to determine whether non-adherence to DMARDs and other variables are predictors of direct hospital related health care costs. Methods DMARD naïve patients diagnosed with inflammatory arthritis were invited for a one year cohort study. Cost measurement comprised hospital-related costs in the first year: consultations, emergency room visits, hospitalization, medical procedures, imaging modalities, medication costs, and laboratory tests. Cost volumes were registered from patient medical files. Non-adherence was continuously measured using electronic monitored medication containers and was defined as the number of days when the amount of observed openings of the container was lower than the amount of expected days with openings. Spearman rank correlations of potential predictors of hospital related costs were calculated. Possible predictors were non-adherence, age, sex, center, baseline disease activity, diagnosis, education level, symptoms of anxiety and depression as measured with the Hospital Anxiety and Depression Scale (HADS), number of comorbidities, and all subscales from the Beliefs About Medication Questionnaire (BMQ); necessity, concerns, general harm and general overuse. Results Of the 275 invited patients, 202 were willing to participate. Six patients were either lost to follow up in the clinic or lost to follow up in the study, which left 194 patients. 74.7% had RA, 20.6% had psoriatic arthritis and 4.6% undifferentiated arthritis. 30.9% of the patients were more than 20% non-adherent over the one-year follow up period to at least one DMARD. The mean (median) rheumatology-related costs per year were € 1714.42 (SD € 2489.20) (median € 976.44 IQR € 615.37–€ 1590.22). The mean (median) total costs per year were € 2211.05 (SD € 3033.35) (median € 1189.99 IQR € 674.95–€ 2043.58). Table 1 shows the mean cost volumes and costs per category. Table 2 shows the Spearman rank correlations of eligible predictors of costs. There were interactions between age and comorbidity; anxiety and depression with baseline DAS28; comorbidity and anxiety. Non-adherence, anxiety and depression and baseline DAS28 contribute to rheumatology hospital costs univariately. Conclusions There is an association between non-adherence and hospital costs, which suggests that applying non-adherence interventions reduces rheumatology costs. Disclosure of Interest None declared

FRI0338 Non-Adherence to Disease Modifying Antirheumatic Drugs in the First Year After Diagnosis: Comparing Three Adherence Measures in Early Arthritis Patients

Background Non-adherence to conventional DMARDs is an important indicator for the effectiveness of treatment in early arthritis patients. Reported non-adherence rates differ widely, because studies use different adherence measures. Objectives This study compared three methods to ascertain how non-adherence should be measured: a validated self-report questionnaire: the Compliance Questionnaire Rheumatology (CQR), the intracellular uptake of methotrexate (MTX) in the form of methotrexate-polyglutamates (MTXPGs) and the electronic measurement of adherence with Medication Event Monitoring Systems (MEMS). Methods Adult patients diagnosed with inflammatory arthritis who started DMARDs were included in a cohort study. MTXPGs were collected and the CQR was filled out after 3, 6, 9 and 12 months of treatment. Non-adherence was continuously measured with MEMS. When there was a discordance between the observed opening and the expected opening of the MEMS cap, this was assigned as a non-adherence event. Relations of MEMS non-adherence proportion with CQR score and MTXPGs were determined with Spearman rank correlations. Sensitivity and specificity of respectively the CQR score against a MEMS 83% (minimum two weeks of non-adherence) cut-off score was calculated at 3, 6, 9 and 12 months. The same applied to the MTX-PGs against a MEMS 84% cut-off score and the MTXPGs against a CQR cut-off score. To assess the influence of adherence measured with MEMS on MTXPGs, an univariate and multivariate linear regression (backward selection, criterion for deletion p>0.10) with MTXPGs as dependent variable and with non-adherence measured with MEMS the 12 weeks before MTXPG measurement (continuous score), age, gender, time of treatment and dosage as independent variables was performed. Results Two hundred and one patients entered the study. As measured with MEMS, non-adherence rates varied over time and between different DMARDs (figure 1). For sulfasalazine and hydroxychloroquine, the non-adherence rates were highest. For all medicines, except for prednisone, the non-adherence rate rose over time. The CQR did only weakly correlate (-0.255) with the MEMS non-adherence proportion at 9 months of therapy and was not associated with MTXPGs. Only at 9 months and 12 months, the ROC curves showed some discrimination between non-adherence measured with MEMS against the CQR score. Non-adherence (β -28,3, p=0.078), time of treatment in weeks (β 1.5, p<0.00) and age (β 1.83, p<0.00) contributed to MTXPGs at 12 months. Conclusions Non-adherence percentages for all DMARDs rise over time, except for prednisone. This might be explained by the fact that patients immediately experience the effect of prednisone, and that most patients tapered prednisone. The CQR is only slightly associated with MEMS after T2 and not at all with MTXPGs. A stronger relationship between these 2 measurement methods was expected. The relatively low relationship may be related to individual differences in the uptake of MTX. We have to learn more about the uptake of MTX over time per patient, before we can use MTXPGs in daily practice as a non-adherence measure. Disclosure of Interest None declared