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

Michaud, Kaleb; Vrijens, Bernard; Tousset, Eric; Pedro, Sofia; Schumacher, Rebecca; Dašić, Gorana; Chen, Connie; Agarwal, Ekta; Suarez‐Almazor, María E.

doi:10.1002/acr2.11079

Cited by 11 publications

(14 citation statements)

References 41 publications

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“…In summary, pharmacokinetic modeling indicates that, for the median patient, the predominant pattern of missed MTX doses after starting MTX, ie, one of isolated, single missed doses, 10 would have little clinical effect, other than delaying the time to reach the therapeutic threshold and/or steady state. For the median patient at steady state, 3 consecutive missed doses would be required for MTXglu levels in red blood cells to fall below the therapeutic range.…”

Section: Discussionmentioning

confidence: 99%

“… 8 Patterns of missed MTX doses over 24 weeks in clinical practice were extracted from a study of adherence in patients participating in the National Data Bank (NDB) for rheumatic diseases. 9 , 10 Adherence data were measured using a Medication Event Monitoring System (MEMS) and presented in the form of a “heat map”, a color-coded graph of the number of doses taken each week by each patient. 10 Dosing patterns were used for selected patients with instances of single missed doses (patients 006, 0021, 0034), or of 2 consecutive (patients 0017, 0027) or 3 consecutive (patients 008, 0011) missed doses.…”

Section: Methodsmentioning

confidence: 99%

“…7,8 Patterns of MTX dose taking in clinical practice were extracted from the NDB study of 60 rheumatoid arthritis patients using MEMS. 10 Patients included in the NDB study were currently taking oral MTX that had been initiated ≤12 months prior to study enrollment. At the time of the most recent questionnaire, the mean (SD) MTX dosage was 14.1 (5.5) mg/week.…”

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confidence: 99%

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Effect of Missed Doses on the Therapeutic Effect of Methotrexate for Rheumatoid Arthritis: A Pharmacokinetic Modeling Study

Morrison¹,

Stauffer²,

Kaufman³

2021

OARRR

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Introduction Patients rarely, if ever, take their medications exactly as prescribed. The extent to which missed doses interfere with a drug’s therapeutic effect remains unclear. Methods After weekly oral dosing of methotrexate (MTX) for rheumatoid arthritis, its polyglutamate derivatives (MTXglu) accumulate in red blood cells, where they are markers for the drug’s therapeutic effectiveness. We used Medication Event Monitoring System data and pharmacokinetic modeling to analyze whether missing MTX doses causes the MTXglu level in red blood cells to fall below the range associated with the drug’s clinical effect. Results For patients initiating oral MTX, the threshold for clinical effectiveness and the steady state level were reached in medians of 6 weeks and 22 weeks, respectively. For patients at steady state who discontinued MTX, the MTXglu level fell below the therapeutic threshold after a median of 3 weeks. After initiating MTX, single missed doses did not cause a loss of therapeutic effect in the median patient if they occurred after 10 weeks, while runs of ≥3 consecutive missed doses did cause the MTXglu level to fall below the therapeutic threshold. Conclusion While there is considerable variation between patients, pharmacokinetic modeling indicates that instances of isolated single missed doses of MTX typically will not cause polyglutamated methotrexate levels in red blood cells to fall below the range associated with the therapeutic effect. Runs of ≥3 consecutive missed doses, however, are typically expected to result in a loss of the therapeutic effect.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Effect of Missed Doses on the Therapeutic Effect of Methotrexate for Rheumatoid Arthritis: A Pharmacokinetic Modeling Study

Morrison¹,

Stauffer²,

Kaufman³

2021

OARRR

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“…1,2 However, previous research revealed that medication adherence to DMARDs ranged from 30-107%, depending on the measurement methods used to assess medication-taking behavior. [3][4][5] Non-adherence to DMARDs is associated with higher disease activity scores and an increased risk of radiographic damage. 2,[6][7][8] Since irreversible articular damage mainly occurs early in the course of RA, with most rapid radiologic progression during the first two years after diagnosis, it is likely that patients with early RA will benefit most from adherence-improving interventions.…”

Section: Introductionmentioning

confidence: 99%

“… 13 , 14 Electronic devices, such as Medication Event Monitoring Systems (MEMS), register time intervals between consecutive openings of MEMS bottles and, therefore, provide insight in medication adherence patterns of patients based on device usage. 5 , 14 , 16 , 17 These data can be used to (1) confront patients with their own medication-taking behavior, and (2) support healthcare professionals in providing tailored and non-judgmental feedback. 14 Such feedback includes the elicitation and strengthening of patients' intrinsic motivation to overcome practical and perceptual barriers to adequate medication intake in daily life (eg concerns about the prescribed medication and beliefs related to medication necessity), and to overcome knowledge gaps regarding DMARD treatment.…”

Section: Introductionmentioning

confidence: 99%

Electronic Monitoring Feedback for Improving Medication Adherence and Clinical Outcomes in Early Rheumatoid Arthritis: A Randomized Clinical Trial

Heuckelum¹,

Ende²,

Dulmen³

et al. 2021

PPA

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Background: Non-adherence to medication (range 30-107%) is a major issue in patients with rheumatoid arthritis (RA). Previous research has shown that electronic monitoring feedback (EMF) might be an effective strategy to improve medication adherence in chronic conditions. Therefore, this study investigated the effectiveness of electronic monitoring feedback in patients with early RA to improve medication adherence and clinical outcomes compared to usual care.Methods: An open-label randomized clinical trial was performed to compare EMF with standard care during a 12-month follow-up period on two sites of the Sint Maartenskliniek (Nijmegen and Boxmeer) in the Netherlands. Patients were eligible if they: (1) had a (working) diagnosis of early RA, (2) were currently using methotrexate, (3) were aged ≥18 years, and (4) had a life expectancy of ≥12 months. Primary outcome was the difference in proportion of non-adherent patients measured with the Compliance Questionnaire on Rheumatology after 12 months. Secondary outcomes were beliefs about medicines, medication adherence measured with the MMAS-8 ® , patients' health status, prescription of biologic DMARDs, and disease activity after 12 months. Results: Of the 367 initially-invited patients, 93 patients with early RA agreed to participate in this study. No significant difference was found in the proportion of non-adherent patients between the intervention arm and the usual care arm after 12 months follow-up (60.0% and 61.3%, p=0.93, respectively). Patients in the intervention arm tended to discontinue methotrexate earlier than patients in the usual care arm (median time in weeks: 15.7 (9.1-33.6) and 21.9 (19-28.4), respectively, p=0.31), whereas patients in the usual care arm tended to initiate biologic DMARDs earlier than those in the intervention arm (median time in weeks: 11.9 (5.7-22) and 17 (9.9-40.9), respectively, p=0.55). Conclusion:This study illustrates the challenge of targeting non-adherence with EMF in patients with early RA and shares important lessons learned about designing adherence intervention trials with respect to study attrition, accounting for drug survival, intervention fidelity, intervention uptake, and technical aspects.

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

Michaud,

Pedro,

Tousset

et al. 2023

ACR Open Rheumatology

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ObjectiveTo 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).MethodsEligible 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.ResultsOf 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.ConclusionWe 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.

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

Cited by 11 publications

References 41 publications

Effect of Missed Doses on the Therapeutic Effect of Methotrexate for Rheumatoid Arthritis: A Pharmacokinetic Modeling Study

Effect of Missed Doses on the Therapeutic Effect of Methotrexate for Rheumatoid Arthritis: A Pharmacokinetic Modeling Study

Electronic Monitoring Feedback for Improving Medication Adherence and Clinical Outcomes in Early Rheumatoid Arthritis: A Randomized Clinical Trial

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

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