Infliximab use in the Netherlands: Uptake and characteristics of originator and biosimilars over time.

AIMS: The objective of this retrospective cohort study was to provide an overview of the utilization of originator and biosimilar infliximab in the Netherlands. METHODS: All infliximab dispensings were selected from the PHARMO In-patient Pharmacy Database from 2002-2018. Descriptive analyses were performed in order to characterise initiators and to describe switching patterns over time. RESULTS: Overall, 3840 patients with 61 274 infliximab dispensings were identified. 2496 patients initiated an originator infliximab and 777 patients initiated a biosimilar infliximab. Overall, 57% of the patients was female and mean age was 43.2 years. Both originators and biosimilars were mostly prescribed by gastroenterologists, followed by internists and rheumatologists. After market authorisation of the first biosimilar, the proportion of new patients initiating the biosimilar increased from 39% in 2015 to 91% in 2018. Out of 704 patients eligible for switching 34% switched. Among switchers, the proportion of females was 60% and mean age at index was 45.1 years. Among nonswitchers, 55% were female and mean age was 39.8 years. The median time to switch was 1.7 years and switchers were most frequently initiated on infliximab by a rheumatologist (42%), while nonswitchers were most frequently initiated by a gastroenterologist (42%). CONCLUSION: The results of this large population-based cohort show an increase in biosimilar initiation in daily clinical practice. The number of switchers remains relatively low as nonmedical switch is not encouraged in the Netherlands.

Differences in medication reconciliation interventions between six hospitals: a mixed method study.

BACKGROUND: Although medication reconciliation (MedRec) is mandated and effective in decreasing preventable medication errors during transition of care, hospitals implement MedRec differently. OBJECTIVE: Quantitatively compare the number and type of MedRec interventions between hospitals upon admission and discharge, followed by a qualitative analysis on potential reasons for differences. METHODS: This explanatory retrospective mixed-method study consisted of a quantitative and a qualitative part. Patients from six hospitals and six different wards i.e. orthopaedics, surgery, pulmonary diseases, internal medicine, cardiology and gastroenterology were included. At these wards, MedRec was implemented both on hospital admission and discharge. The number of pharmacy interventions was collected and classified in two subcategories. First, the number of interventions to resolve unintended discrepancies (elimination of differences between listed medication and the patient's actual medication use). And second, the number of medication optimizations (optimization of pharmacotherapy e.g. eliminating double medication). Based on these quantitative results and interviews, a focus group was performed to give insight in local MedRec processes to address differences in context between hospitals. Descriptive analysis (quantitative) and content analysis (qualitative) was used. RESULTS: On admission 765 (85%) patients from six hospitals, received MedRec by trained nurses, pharmacy technicians, pharmaceutical consultants or pharmacists. Of those, 36-95% (mean per patient 2.2 (SD ± 2.4)) had at least one discrepancy. Upon discharge, these numbers were among 632 (70%) of patients, 5-28% (mean per patient 0.7 (SD 1.2)). Optimizations in pharmacotherapy were implemented for 2% (0.4-3.7 interventions per patient upon admission) to 95% (0.1-1.7 interventions per patient upon discharge) of patients. The main themes explaining differences in numbers of interventions were patient-mix, the type of healthcare professionals involved, where and when patient interviews for MedRec were performed and finally, embedding and extent of medication optimization. CONCLUSIONS: Hospitals differed greatly in the number of interventions performed during MedRec. Differences in execution of MedRec and local context determines the number of interventions. This study can support hospitals who want to optimize MedRec processes.

Healthcare professionals' perceptions on barriers and facilitators to DMARD use in rheumatoid arthritis.

BACKGROUND: Disease-modifying anti-rheumatic drugs (DMARDs) are the cornerstone of rheumatoid arthritis (RA) treatment. However, the full benefits of DMARDs are often not realized because many patients are sub-optimally adherent to their medication. In order to optimize adherence, it is essential that healthcare professionals (HCPs) understand patients' barriers and facilitators for medication use. Insight in these barriers and facilitators may foster the dialogue about adequate medication use between HCPs and patients. What HCPs perceive as barriers and facilitators has, so far, scarcely been investigated. This study aimed to identify the perceptions of HCPs on patients' barriers and facilitators that might influence their adherence. METHODS: This qualitative study was performed using semi structured in-depth interviews with HCPs. An interview guide was used, based on an adjusted version of the Theoretical Domains Framework (TDF). Thematic analysis was conducted to identify factors that influence barriers and facilitators to DMARD use according to HCPs. RESULTS: Fifteen HCPs (5 rheumatologists, 5 nurses and 5 pharmacists) were interviewed. They mentioned a variety of factors that, according to their perceptions, influence DMARD adherence in patients with RA. Besides therapy-related factors, such as (onset of) medication effectiveness and side-effects, most variation was found within patient-related factors and reflected patients' beliefs, ways of coping, and (self-management) skills toward medication and their condition. In addition, factors related to the condition (e.g., level of disease activity), healthcare team and system (e.g., trust in HCP), and social and economic context (e.g. support, work shifts) were reported. CONCLUSIONS: This study provided insights in HCPs' perceptions of the barriers and facilitators to DMARD use patients with RA. Most factors that were mentioned were patient-related and potentially modifiable. When physicians understand patients' perceptions on medication use, adherence to DMARDs can probably be optimized in patients with RA leading to more effectiveness of treatment outcomes.

Ranking facilitators and barriers of medication adherence by patients with inflammatory arthritis: a maximum difference scaling exercise.

INTRODUCTION: Facilitators and barriers of adherence to disease-modifying anti-rheumatic drugs (DMARDs) have been identified by patients with inflammatory arthritis earlier. However, the relative importance from the patients' perspective of these factors is unknown. Knowledge on this ranking might guide the development of interventions and may facilitate targeted communication on adherence. This study aims to examine 1) the relative importance patients attach to facilitators and barriers for DMARDs adherence, and 2) the relationship between patient characteristics and ranking of these factors. METHODS: One hundred twenty-eight outpatients with inflammatory arthritis; (60% female, mean age 62 years (SD = 12), median disease duration 15 years, IQR (7, 23) participated in a Maximum Difference scaling exercise and ranked 35 items based upon previously identified facilitators and barriers to medication adherence. Hierarchical Bayes estimation was used to compute mean Rescaled Probability Scores (RPS; 0-100) (i.e. relative importance score). Kendall's coefficient of concordance was used to examine a possible association between patients' characteristics (i.e. age, sex and educational level) and ranking of the items. RESULTS: The three most important items ranked by patients were: Reduction of symptoms formulated as "Arthritis medications help to reduce my symptoms" (RPS = 7.30, CI 7.17-7.44), maintaining independence formulated as "I can maintain my independence as much as possible" (RPS = 6.76, CI 6.54-6.97) and Shared decision making formulated as "I can decide -together with my physician- about my arthritis medications" (RPS = 6.48, CI 6.24-6.72). No associations between patient characteristics and ranking of factors were found. CONCLUSIONS: Reducing symptoms, maintaining independency and shared decision making are patients' most important factors for DMARDs adherence. This knowledge might guide the development of interventions and may facilitate communication between health professionals and their patients on medication adherence.

Associations between personality traits and adequate home storage of drugs in older patients.

The objective of this study was to investigate the association between personality traits of older patients and adequate home storage of drugs. Forty-four participating Dutch community pharmacists randomly selected each up to four community-dwelling elderly patients (≥65 years) who were using at least one prescription drug. The Big Five Inventory was used to assess the personality traits - 'openness', 'conscientiousness', 'extraversion', 'agreeableness' and 'neuroticism' - of patients. An assessment of adequate home storage of drugs was made using a summed composite score for each patient ranging from zero (adequate storage) to three (inadequate storage) was based on storage criteria representing quality, information and level of storage organization. A 51.2% of the patients stored drugs adequately in accordance with all quality ("Q") and information ("I") criteria. A high level of drug storage organization was found in 70.8% of patients. Forty-three patients (31.4%) stored their drugs adequately based on all storage criteria (composite storage score 0). No associations between personality dimensions and adequate drug storage were found. Having a lower number of drugs was associated with adequate drug home storage (ORadjusted 0.86; 95% CI: 0.77-0.96). In conclusion, this study suggests that personality is not associated with adequate home storage of drugs in older patients.

Disease burden of knee osteoarthritis patients with a joint replacement compared to matched controls: a population-based analysis of a Dutch medical claims database.

OBJECTIVE: On a population level, the incidence of knee prostheses (KPs) has increased, but excess health care costs per patient, compared to matched controls without a KP, in the years surrounding these procedures and their determinants are largely unknown. We therefore aimed to provide estimates of age- and sex-specific incidence of KPs, revision KPs, and prosthesis complications in patients with knee osteoarthritis (OA) and to determine excess health care costs in the years surrounding surgery compared with matched controls. METHODS: All KPs in OA patients in the Achmea Health Database were identified as well as up to four controls. Incidence rates of KPs, revisions, and complications from 2006 to 2013 were determined. Annual health care cost and excess costs (over matched controls) preceding, during, and after surgery were calculated and their determinants were evaluated. RESULTS: The increased incidence of KPs, revisions, and complications was strongest in younger age categories and men. The average costs per patient were relatively stable between 2006 and 2012. KP patient's annual health care costs increased towards the year of surgery. After surgery, costs decreased, but remained higher as compared to costs prior to surgery. High post-surgery costs were mainly associated with subsequent revisions or additional KPs, but costs were also higher in females, lower age categories, and lower social economic status. CONCLUSION: These results underscore the increasing burden and medical need associated with end-stage OA, especially in younger age categories. Improvement of guidelines tailored to individual patient groups aimed at avoiding complications and revisions is required to counteract this increasing burden.

The Impact of Inadequate Temperature Storage Conditions on Aggregate and Particle Formation in Drugs Containing Tumor Necrosis Factor-Alpha Inhibitors.

PURPOSE: To measure aggregate and particle formation in tumor necrosis factor-alpha (TNF-α) inhibitors etanercept, adalimumab and certolizumab pegol product samples after exposure to freezing temperature conditions similar to storage conditions previously observed in patients' homes. METHODS: TNF-α inhibitors in their original primary and secondary packaging were exposed to 32 freeze-thaw cycles (-10°C for 120min/5°C for 60 min) or continuous low storage temperature (-20°C for 96 h) before thawing at 2-8°C. Non-stressed products were used as controls. The products were analyzed by high pressure size exclusion chromatography (HP-SEC), dynamic light scattering (DLS), nanoparticle tracking analysis (NTA), micro-flow imaging (MFI) and second derivative ultraviolet (UV) spectroscopy. RESULTS: Ten out of twenty-one stressed product samples (47.6%) showed increased particle numbers in the submicron and micron size range when compared to controls. For each product, DLS, MFI and NTA detected an increase in particle level in at least one stressed syringe (both continuous freezing and freeze-thaw), whereas HP-SEC and UV spectroscopy showed no differences between stressed and non-stressed products. CONCLUSION: TNF-α inhibitors are relatively resistant to freezing temperatures similar to storage conditions previously observed in patients' homes. However, almost half of the stressed product samples showed formation of particles in the submicron and micron size range.

Pharmacokinetics of 400 mg ropivacaine after periarticular local infiltration analgesia for total knee arthroplasty.

BACKGROUND: Although considered safe, no pharmacokinetic data of high dose, high volume local infiltration analgesia (LIA) with ropivacaine without the use of a surgical drain or intra-articular catheter have been described. The purpose of this study is to describe the maximum total and unbound ropivacaine concentrations (Cmax , Cu max ) and corresponding maximum times (Tmax , Tu max ) of a single-shot ropivacaine (200 ml 0.2%) and 0.75 mg epinephrine (1000 µg/ml) when used for LIA in patients for total knee arthroplasty. METHODS: In this prospective cohort study, 20 patients were treated with LIA of the knee for primary total knee arthroplasty. Plasma samples were taken at 20, 40, 60, 90, 120, 240, 360 min and at 24 h after tourniquet release, in which total and unbound ropivacaine concentrations were determined. RESULTS: Results are given as median [IQR]. Highest ropivacaine concentration (Cmax ) was 1.06 µg/ml [0.34]; highest unbound ropivacaine concentration (Cu max ) was 0.09 µg/ml [0.05]. The corresponding time to reach the maximum concentration for total ropivacaine was 312 min [120] after tourniquet release, and for the unbound fraction 265 [110] min after tourniquet release. CONCLUSION: Although great inter-individual variability was found between the maximum ropivacaine concentrations, both maximum total and unbound serum concentrations of ropivacaine remained well below the assumed systemic toxic thresholds of 4.3 and 0.56 µg/ml.

Dose reduction of tocilizumab in rheumatoid arthritis patients with low disease activity.

OBJECTIVES: Tocilizumab is effective in the treatment of rheumatoid arthritis (RA). A proportion of patients achieve low disease activity using a lower than registered starting dose. We investigated the feasibility of dose reduction to 4 mg/kg in patients who reached low disease activity at the registered dose of 8 mg/kg. METHODS: In this retrospective study, data were collected of 22 patients successfully treated with tocilizumab 8 mg/kg for about 6 months and tapered to 4 mg/kg because of low disease activity. In case of loss of disease control, the dose could be increased again to 8 mg/kg. The percentage of patients with successful dose reduction and difference in DAS28 was described. RESULTS: Mean DAS28 at time of dose reduction was 2.3 (SD 0.9). After 3 and 6 months follow-up, 77% (95% CI 54-91) and 55% (95% CI 32-76) of patients had successfully reduced the dose without losing disease control, respectively. DAS28 at 3 and 6 months was somewhat higher than baseline, 2.7 (SD 1.2) and 2.5 (SD 1.0) respectively. All patients who experienced worsening of disease activity after dose reduction regained low disease activity after dose escalation. CONCLUSIONS: Dose reduction of tocilizumab seems feasible in a substantial proportion of patients. Dose escalation after flare was effective in all patients.

Higher infection risk for JAK inhibitors tofacitinib and baricitinib compared to subcutaneous biological DMARDs.

INTRODUCTION: Rheumatoid arthritis (RA) is usually treated with disease modifying antirheumatic drugs (DMARDs), including biological DMARDs (bDMARDs) and more recently, Janus kinase inhibitors (JAKi). Randomized trials suggest similar infection risks for JAKi and bDMARDs, but real-world data are scarce. METHODS: From a nationally representative prescription database, adult RA patients starting a new JAKi or bDMARD between August 1st, 2018, and January 31st, 2021, were included. Prescriptions of antibiotic, antiviral or antifungal medication were used as proxy for infections. Infection incidence rates (IR) were compared between JAKi and bDMARDs and infection risks were estimated using multilevel Poisson regression adjusted for follow-up time and potential confounders and stratified for age < 65 and ≥ 65 years. RESULTS: In 14,989 patients, we identified 20,050 treatment episodes with either JAKi or bDMARDs. The infection IR was significantly higher in JAKi (48/100 patient years) compared bDMARDs (35/100 patient years, adjusted incidence rate ratio (IRR) 1.22, 95% CI 1.12-1.33). More herpes zoster infections were seen in JAKi compared to bDMARDs (adjusted IRR 2.65, 95% CI 1.94-3.60). No significant differences in infection IRs were found comparing JAKi baricitinib and tofacitinib. In older patients, infection IRs were higher, but IRRs were similar between age groups. CONCLUSION: In comparison to bDMARDs, JAKi are associated with a slightly higher infection risk and a higher risk of herpes zoster specifically. In older patients, infection IRs are higher but similar infection risks for JAKi and bDMARDs are observed. No differences in infection risk between tofacitinib and baricitinib were found. Key Points • Compared to bDMARDs, JAKi are associated with a slightly higher infection risk for all ages • An increased risk of herpes zoster in patients who use JAK inhibitors was confirmed • No significant differences in infection incidence were found between tofacitinib and baricitinib.

Key factors underlying the willingness of patients with cancer to participate in medication redispensing.

BACKGROUND: Redispensing medication unused by patients to other patients could reduce the environmental burden of medication waste. Simultaneously, associated financial loss could be reduced, particularly for expensive medication such as oral anticancer drugs. An important determinant for successful medication redispensing is patient participation. OBJECTIVE(S): To identify key factors underlying the willingness of patients with cancer to participate in the redispensing of unused oral anticancer drugs. METHODS: Semi-structured interviews via telephone or video call were conducted with adult patients diagnosed with cancer from two Dutch hospitals. The interview guide was framed using the COM-B model for behavioural change, to elicit patients' capability, opportunity and motivation to participate in medication redispensing. Questions were related to patients' willingness to accept redispensed medication, reasons thereof, perceived concerns and needs. Inductive thematic analysis was applied. RESULTS: Seventeen patients (aged 38-82 years, 71% female), with nine different types of cancer participated. The majority of participants supported medication redispensing. Four categories of key factors underlying the willingness of patients with cancer to participate in medication redispensing were identified. First, the driver for participation was having positive societal impact, relating to affordability and sustainability of healthcare. Second, having trust in product quality was a requirement, influenced by preconceived beliefs, quality assurance and patients' knowledge of this process. Third, a facilitator for participating in medication redispensing was adequate provision of information. This concerned awareness of medication waste, information about medication redispensing, support from healthcare providers and other patients, and insight into medication dispensing history. Last, a convenient process for returning unused medication to pharmacies would facilitate participation in medication redispensing. CONCLUSIONS: The willingness of patients with cancer to participate in medication redispensing relates to a drive for achieving positive societal impact, provided that medication is of high quality, there is adequate information provision and a convenient process.

Making the rheumatologist aware of patients' non-adherence does not improve medication adherence in patients with rheumatoid arthritis.

OBJECTIVES: We have developed an instrument that provides the physician structured information about medication use and patients' (non-)adherence. This study aimed to determine the effectiveness of this instrument on adherence and medication beliefs in outpatients with rheumatoid arthritis (RA). METHODS: In this within-subject controlled prospective cohort study, 50 outpatients were assessed during three consecutive visits to their rheumatologist. At these three points in time, patients' adherence, medication beliefs, satisfaction about information about medication, and physical functioning were measured using validated self-report questionnaires. An intervention was scheduled during the second visit. The intervention consisted of a written report informing the physician about medication use and adherence to medication for each patient. The effectiveness of the intervention was evaluated by comparing outcome measures at the third visit to the same measures assessed prior to the intervention. RESULTS: At baseline, 30% of the patients (n = 50) were non-adherent. No significant changes in adherence were found between the first and second visit prior to the intervention. Adherence did not change after the intervention, compared to both of the adherence assessments prior to the intervention. Beliefs about medication, patients' satisfaction about information on medication, and physical functioning were also not significantly altered. CONCLUSION: Supplying the rheumatologist a report with information about medication use and adherence did not change adherence or patients' beliefs about medication. Further research is necessary to ensure effective support for adherence for individual patients with RA.

Effect of medication reconciliation on patient reported potential adverse events after hospital discharge.

BACKGROUND: Although medication reconciliation (MedRec) is effective in decreasing medication discrepancies, the effectiveness on Adverse Events (AEs) is very scarce. The objective of this study was to assess the effect of MedRec by a pharmacy team on patient-reported, potential AEs post-discharge. METHODS: This was a multicenter prospective intervention study with before-after design at two Dutch hospitals. Participants were patients aged ≥18 years admitted for more than 48 h using three or more prescription medications upon discharge. Patients in the control group received usual care. In the intervention period, a trained team of pharmacy staff executed medication reconciliation consisting of patient education upon admission and discharge, review of prescribed medication to identify errors, and information transfer to primary care. To address the primary outcome, the difference in proportion of patients with one or more potential AEs was measured by a structured telephone interview, two weeks after discharge between usual care and intervention group. To address the second outcome, the difference in median number of potential AEs per patient was calculated. Other outcomes assessed included the association between the intervention and patient characteristics. RESULTS: In total, 221 (138 usual care and 83 intervention) patients were included. The proportion of control and intervention patients with AEs was 88.4% and 86.7% respectively (p > 0.05). The median number of potential AEs per patient was lower in the intervention group compared with usual care (1.1 vs. 2.1, p < 0.0001). Being in the intervention arm was associated with less potential AEs (RR 0.5, 95% CI [0.4-0.6]), whereas being previously admitted was associated with a higher number of potential AEs (RR 1.3, 95% CI [1.1-1.5]). The effect of the intervention on the number of potential AE was stronger among women compared with men (p = 0.04). CONCLUSION: Although the intervention did not decrease the proportion of patients with AEs, a significant reduction in the median number of potential AEs after hospital discharge between the intervention and usual care group was observed.

Medication management during transitions from hospital to home: a focus group study with hospital and primary healthcare providers in the Netherlands.

Background Medication management is jeopardized during a patient's transition from hospital to home. Insight is required from both hospital and primary healthcare providers on how care should be organised to achieve continuity of medication management. Objective This study aimed to identify perspectives of hospital and primary healthcare providers on barriers to the continuity of medication management during a patient's transition from hospital to home and facilitators to overcome these. Setting A qualitative descriptive study was conducted within hospital and primary healthcare settings in the Netherlands. Method Two focus groups were performed with two community care registered nurses, two community pharmacists, four general practitioners, two hospital nurses, two hospital pharmacists, four outpatient pharmacists, two pharmacy technicians, and one physician. A semi-structured interview guide was used to identify perspectives of participants on barriers to continuity of medication management and facilitators to overcome these. Data were analysed following thematic content analysis. Main outcome measure Barriers to the continuity of medication management during a patient's transition from hospital to home would be enumerated, along with facilitators to overcome these barriers. Results Three main themes of barriers and facilitators were identified: (1) healthcare provider collaboration, including the transfer of medication information and effective collaboration; (2) patient's medication use, including information about medication, personalised care, and supervision after discharge; and (3) organisation of healthcare, including the connection between information systems and the supply of medication. Conclusion Barriers and facilitators to continuity of medication management during the transition from hospital to home occur at the provider, patient, and healthcare-system levels. Future interventions should focus on all levels through interprofessional healthcare teams, tailoring care to patient needs, and on the use of a uniform, nationwide patient electronic health record.

[Better compliance with therapy in preventative medication use]. / Betere therapietrouw bij preventief medicatiegebruik.

Prescription of medication is one of the most common medical interventions. Just half of patients use a prescribed preventative medication in accordance with the doctor's instructions; this leads to a smaller effect from the medication, side effects and higher care costs. Therapy-non-compliant patients are hardly recognisable on the basis of clinical, demographic or medication-related characteristics. The prescriber can make use of pharmacist data, questionnaires, or technical aids, or broach the subject with the patient to discover whether or not the patient is therapy-compliant. Reasons for non-compliance with therapy can be roughly divided into unintentional or practical reasons and intentional reasons. Tailored intervention can be offered on the basis of the underlying reasons.

[Reducing medication waste; a challenge for care providers and society]. / Geneesmiddelverspilling verminderen.

Annually, in the Netherlands, at least 100 million euro is wasted on unused medication. This waste not only has considerable economic implications, but is also associated with an unnecessary burden on the environment and suboptimal care due to nonadherence to therapy. The reasons for medication wastage can be found throughout the entire pharmaceutical supply and use chain, which includes manufacturers, distributors/wholesalers, prescribers, pharmacists and patients, both in the community and hospital setting. A number of strategies are needed to minimize the waste of medication, one of which should be a preventative approach. Involvement of all stakeholders in the supply chain is a prerequisite for a successful outcome. It is important that prescribers are aware of the extent and consequences of wastage, and of the possible ways to reduce it.

A pilot study examining patient preference and satisfaction for ava®, a reusable electronic injection device to administer certolizumab pegol.

Background: Anti-tumor necrosis factor (anti-TNF) adherence is suboptimal. ava®, a reusable electromechanical self-injection device (e-Device) developed for certolizumab pegol (CZP) administration, aims to overcome some barriers to increase adherence. This study evaluates patient experience of the e-Device and its training materials and determines patient device preference.Methods: CZP-treated patients were recruited from the Netherlands, Denmark and Sweden. Patients completed a pre-injection Assessment of Self-Injection (ASI) questionnaire investigating self-injection perception. After training, patients administered 3 consecutive self-injections using the e-Device, patient experience of each was assessed using the post-injection ASI. An additional questionnaire evaluated training materials. After Injection 3, patients indicated their preference: the e-Device or their previous device.Results: 59 patients participated; most rated the e-Device highly for satisfaction, self-confidence and ease of use. The (negative) feelings and pain and skin reactions domains had low ratings. Post-injection ASI domain scores were similar following each of the 3 e-Device injections. Training materials were rated highly (video: 8.4/10; step-by-step guide: 8.4/10). 57.1% (32/56) patients preferred the e-Device over their previous self-injection device.Conclusions: Patients were satisfied with the e-Device and most preferred it over other self-injection devices. By improving patient experience, the e-Device may help increase medication adherence.

Quantity and economic value of unused oral anti-cancer and biological disease-modifying anti-rheumatic drugs among outpatient pharmacy patients who discontinue therapy.

BACKGROUND: Patients sometimes discontinue the use of expensive oral anti-cancer drug (OACD) or biological disease-modifying anti-rheumatic drug (bDMARD) therapies early, leading to medication waste if the patient has not used all dispensed medication. OBJECTIVE: To determine the proportion of patients who have unused OACDs or bDMARDs after therapy discontinuation, and the quantity and economic value of these unused medications. Furthermore, patients' reasons for therapy discontinuation and their disposal method for unused medications were determined. METHODS: In a retrospective follow-up study using a Dutch outpatient pharmacy database, patients (≥18 years) who did not refill an OACD or bDMARD prescription, dispensed between November 2015 and February 2016, within two weeks of the prescription end date were contacted by phone and asked about their unused medication and reasons thereof. The economic value was calculated using Dutch medication prices. Data were descriptively analyzed in STATA13. RESULTS: The database included 1173 patients, of whom 159 likely had discontinued therapy and were contacted. Of these, 88 patients were excluded (39 refilled, 47 missing, and 2 other). Of the 71 patients who had discontinued therapy, 39 (54.9%) had unused medications, comprising 22 OACD users (mean age 63.0 (SD ±â€¯15.9) years, 50.0% female) and 17 bDMARD users (mean age 50.7 (SD ±â€¯13.5) years, 47.1% female). A total of 59 packages were unused, with a total value of €60,341. Unused OACD packages and bDMARD packages had median values of €179 (IQR €24-2487) and €992 (IQR €681-1093), respectively. Patients primarily discontinued therapy due to adverse or insufficient effects. CONCLUSIONS: This study illustrates that more than half of patients discontinuing OACD or bDMARD therapies have unused medication. This emphasizes the need for waste-reducing interventions.

Implicit and explicit attitudes towards disease-modifying antirheumatic drugs as possible target for improving medication adherence.

OBJECTIVE: This study aims to explore the contribution of implicit attitudes and associations towards conventional disease-modifying antirheumatic drugs (cDMARDs), alongside explicit measures, on medication-taking behaviour and clinical outcomes in adult patients with rheumatoid arthritis (RA). METHODS: In this observational study, implicit attitudes (positive-negative) and health-related associations (health-sickness) were measured with Single Category Implicit Association Tests, whereas explicit outcomes were measured with a bipolar evaluative adjective scale and the Beliefs about Medicines Questionnaire Specific. The primary outcome of this study was medication-taking behaviour subjectively measured by self-report (i.e. validated Compliance Questionnaire on Rheumatology) and objectively measured with electronic drug monitors over a 3 month period. Spearman rank correlations were used to describe correlations between implicit and explicit outcomes. Nested linear regression models were used to assess the additional value of implicit measures over explicit measures and patient-, clinical-, and treatment-related characteristics. RESULTS: Of the 1659 initially-invited patients, 254 patients with RA agreed to participate in this study. Implicit attitudes correlated significantly with necessity-concerns differential (NCD) scores (ρ = 0.13, P = 0.05) and disease activity scores (ρ = -0.17, P = 0.04), whereas implicit health-related associations correlated significantly with mean scores for explicitly reported health-related associations (ρ = 0.18, P = 0.004). Significant differences in age, number of DMARDs, biologic DMARD use, NCD-scores, and self-reported correct dosing were found between the four attitudinal profiles. Nested linear regression models revealed no additional value of implicit measures in explaining self-reported medication-taking behaviour and clinical outcomes, over and above all other variables. CONCLUSION: Implicit attitudes and associations had no additional value in explaining medication-taking behaviour and clinical outcomes over and above often used explicitly measured characteristics, attitudes and outcomes in the studied population. Only age and NCD scores contributed significantly when the dependent variable was correct dosing measured with self-report.

Sustained effect after lowering high-dose infliximab in patients with rheumatoid arthritis: a prospective dose titration study.

OBJECTIVES: In clinical trials only a small subset of patients with rheumatoid arthritis (RA) benefits from higher than standard dose of infliximab (>3 mg/kg/8 weeks). However, dose escalation of infliximab is frequently applied in clinical practice. Individual adjustment of infliximab treatment based on actual disease activity, instead of subjective clinical judgement, could prevent possible unwarranted dose escalation. METHODS: The infliximab dose of all patients with RA treated at our centre was decreased from 5 mg/kg to 3 mg/kg, leaving dosing intervals unaltered. Subsequently patients were followed for at least three infusions. At every visit, 28-joint Disease Activity Score (DAS28), infliximab serum trough levels and anti-infliximab antibody levels were assessed. Inversed European League Against Rheumatism (EULAR) criteria (flare criteria) were used as the endpoint. RESULTS: A total of 18 patients were included in the study. Mean (SD) DAS28 scores before dose reduction and after first and second low dose were 3.2 (1.2), 3.2 (1.8) and 3.3 (1.2), respectively (values not significant). One patient (6%, 95% CI 0% to 17%) developed a persistent flare that subsided after increasing infliximab doses and one patient stopped infliximab because of a lupus-like reaction. In all other patients (n=16) lowering infliximab resulted in unaltered disease activity. Infliximab levels showed that most patients had either low- (<1 mg/litre) or high (>5 mg/litre) serum trough levels. Anti-infliximab antibodies were detected in four patients. CONCLUSION: Infliximab dosages of 5 mg/kg can be lowered in the majority of patients with RA using DAS28-guided dose titration without increase of disease activity. Lowering the dose of infliximab should be considered in every patient receiving higher doses infliximab.