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ARD Online First, published on February 13, 2015 as 10.1136/annrheumdis-2014-206593 Clinical and epidemiological research
EXTENDED REPORT
What are the effects of medication adherence interventions in rheumatic diseases: a systematic review Jessica S Galo,1 Pavandeep Mehat,1,2 Sharan K Rai,2,3 Antonio Avina-Zubieta,2,3,4 Mary A De Vera1,2 Handling editor Tore K Kvien ▸ Additional material is published online only. To view please visit the journal online (http://dx.doi.org/10.1136/ annrheumdis-2014-206593). 1
University of British Columbia Faculty of Pharmaceutical Sciences, Vancouver, British Columbia, Canada 2 Arthritis Research Canada, Richmond, British Columbia, Canada 3 Department of Experimental Medicine, University of British Columbia Faculty of Medicine, Vancouver, British Columbia, Canada 4 Division of Rheumatology, University of British Columbia Faculty of Medicine, Vancouver, British Columbia, Canada Correspondence to Dr Mary De Vera, University of British Columbia Faculty of Pharmaceutical Sciences, 2405 Wesbrook Mall, Vancouver, British Columbia, Canada V6T 1Z3; [email protected] Received 8 September 2014 Revised 13 January 2015 Accepted 15 January 2015
ABSTRACT Objectives Consistent reports of suboptimal treatment adherence among patients with inflammatory arthritis underscore the importance of understanding how adherence can be promoted and supported. Our objectives were to identify and classify adherence interventions; and assess the evidence on the effects of adherence interventions on outcomes of patients with rheumatic diseases. Methods We conducted a mapped search of Medline, Embase and International Pharmaceutical Abstract databases to identify studies meeting inclusion criteria of: (1) patient population with inflammatory arthritis; (2) evaluation of an intervention or programme targeting medication adherence directly or indirectly; (3) reporting of one or more measures of medication adherence and disease outcome; (4) publication in English, French or Spanish. For our first objective, we applied a structured framework to classify interventions according target ( patient vs provider), focus (educational vs behavioural vs affective), implementation (generalised vs tailored), complexity (single vs multifaceted) and provider. For the second objective, we appraised the evidence of effects of interventions on adherence and disease outcomes. Results We identified 23 studies reporting adherence interventions that directly or indirectly addressed treatment adherence in rheumatic diseases and further appraised included RCTs. Interventions that were shown to impact adherence outcomes were generally interventions directed at adherence, tailored to patients and delivered by a healthcare provider. For interventions that were not shown to have impacts, reasons may be those related to the intervention itself, patient characteristics or study methodology. Conclusions Our systematic review shows limited research on adherence interventions in rheumatic diseases with inconsistent impacts on adherence or disease outcome.
INTRODUCTION
To cite: Galo JS, Mehat P, Rai SK, et al. Ann Rheum Dis Published Online First: [please include Day Month Year] doi:10.1136/ annrheumdis-2014-206593
Adherence to long-term pharmacotherapy is paramount to the management of inflammatory arthritis —including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), gout and juvenile idiopathic arthritis ( JIA)—as left untreated, these conditions can result in disability, complications, morbidity and mortality.1–11 Yet systematic reviews have synthesised adherence rates as low as 10% in gout,12 30% in RA13 and 49% in SLE.14
While the problem of medication non-adherence is well described in rheumatology, solutions are not. Systematic reviews on adherence interventions in chronic disease including elderly15 patients with hypertension16 and diabetes17 are available, yet to our knowledge, there are none specifically among patients with rheumatic diseases. A 2014 update of a 2008 Cochrane review of adherence interventions increased included trials in RA from 219 20 to 6.18 However, an extension of this information is needed along with comprehensive knowledge of published evidence in patients with rheumatology. Thus, our objectives were to: (1) identify and classify adherence interventions; and (2) assess the evidence on the effects of adherence interventions on outcomes of patients with rheumatic diseases.
METHODS Literature search strategy We searched Medline (1946–June 2014), Embase (1974–June 2014) and International Pharmaceutical Abstracts (1970–June 2014). We used Medical Subject Headings for concepts underlying our search, ‘medication adherence’, ‘intervention’ and ‘inflammatory arthritis’ and applied keywords for concepts that did not map (see online supplementary table S1). We also conducted a hand search of bibliographies as well as a Google Scholar search.
Study selection Two authors reviewed all titles and abstracts to identify studies meeting the following inclusion criteria: (1) patient population with inflammatory arthritis (eg, RA, SLE, JIA); (2) evaluation of an intervention or programme targeting medication adherence directly or indirectly; (3) reporting of one or more measures of medication adherence and disease outcome; (4) publication in English, French or Spanish. As one of our objectives was to comprehensively identify instances where treatment adherence has been addressed in rheumatic disease, at this point, we did not exclude according to study design. Disagreement between reviewers was resolved by consensus.
Identification of adherence interventions in rheumatic diseases To address our first objective, we classified adherence interventions according to: (1) target (patient vs provider);21 (2) focus (educational vs behavioural vs affective);22 (3) complexity (single vs
Galo JS, et al. Ann Rheum Dis 2015;0:1–7. doi:10.1136/annrheumdis-2014-206593
1
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Clinical and epidemiological research multifaceted);15(4) implementation (generalised vs tailored);15 and (5) provider (eg, physician, nurse, pharmacist) of the intervention. The target refers to the receiver of the intervention.21 The focus of the interventions were categorised as educational (designed to deliver information with a knowledge-based emphasis), behavioural (designed to change adherence by targeting behavioural patterns) or affective (designed to influence adherence through appeals to feelings or social relationships).22 The complexity of the intervention distinguishes ones that have a single focus from those with multiple foci.15 22 Implementation of the intervention may be categorised as tailored to patient or generalised.15 Finally, we specified the provider of the intervention.
Quality assessment of controlled trials of adherence interventions in rheumatic diseases To address our second objective of assessing the evidence on impacts of adherence interventions, we focused on included randomised controlled trials (RCTs). We developed a standardised quality assessment using the Consolidated Standards of Reporting Trials checklist.23 Studies were assessed for quality of the design, conduct and reporting, using the scoring criteria: 0=not done or reported, 0.5=partially done or reported and 1=well done and clearly reported (see online supplementary table S2).
Data extraction and outcome measurement We extracted information including study design, patient population, disease duration, sample size and medications. Our primary outcome was the effect of the intervention on adherence outcomes and we extracted information on whether this was reported or analysed, adherence measure, time point of measurement, value of adherence measure for the intervention and control group, and effect size. We calculated effect size where one was not reported. Specifically, for studies reporting mean values of the adherence measure, we calculated the standardised mean difference (SMD)—the difference of the group means divided by the standard deviation (SD) for the study group24 and for studies reporting adherence in terms of proportion of patients, we calculated the relative risk (RR)—the proportion of adherent patients in the intervention group divided by the proportion of adherent patients in the control group. Our secondary outcome was the effect of the intervention on disease outcomes and where possible, we similarly extracted information as with adherence outcomes. Due to heterogeneity and limited data availability, we could not perform similar calculations to estimate effect sizes for disease outcome measures.
directly target medication adherence, with all but one intervention29 directed at patients with rheumatology. This exception was an instrument providing rheumatologists with structured information about their patients’ non-adherence, which was not shown to have an impact on adherence or disease-related outcomes.29 With respect to focus, 21 interventions incorporated an educational component, one was a behavioural intervention involving text message reminders to patients with SLE,28 and the aforementioned rheumatologist-targeted intervention was classified as affective.29 Fourteen interventions were multifaceted and implementation was tailored to patients in 18 interventions. Interventions were delivered by rheumatologists,20 30–33 nurses,19 25 33–36 pharmacists,25 27 29 36–38 and other professionals including therapists39 and educators.40–44
Effects of adherence interventions in rheumatic diseases We critically appraised 13 RCTs—10 in RA, 2 in SLE and 1 in JIA. We did not include here a pilot RCT of group versus individual counselling for RA34 and a pilot RCT of internet-based self-management with telephone support for JIA.44 Quality scores varied from 9 to 28 out of a maximum possible score of 32 (mean=18.6; median=18.5). We ranked 719 20 27 38–40 43 as having good or high quality (above median) and 6 as having fair or poor quality. Key results of our synthesis are tabulated in table 1. Detailed information on adherence and disease outcomes are provided in online supplementary tables S4 and S5.
Rheumatoid arthritis
We classified adherence interventions described in 23 studies— 16 in RA, 3 in SLE, 1 in gout, 2 in JIA and 1 in unspecified arthritis. Study details along with intervention classifications are in online supplementary table S3. The description of interventions ranged from ‘one-on-one instruction’,25 ‘group education’,26 ‘telephone-based pharmacy advisory’,27 to ‘text message reminders’.28 Fourteen of 23 interventions were designed to
In McEvoy DeVellis et al’s42 study, all patients first participated in a psychosocial interview to assess problems related to their RA. The intervention group then received a problem-solving intervention to address problems identified in the interview.42 Authors cited no significant difference between groups, though did not report data.42 Authors also stated that all patients who participated in study, regardless of group assignment, improved on physical and psychological function measures, which may be attributed to unintended positive effects of the psychosocial interview received by both groups.42 Brus et al20 used group patient education meetings delivered by a rheumatologist four times over 1 month and subsequently at 4 months and 8 months for patients with recent-onset active RA. From reported mean adherence rates of 89±16 and 84±21 in the intervention and control groups, respectively, we estimated a SMD of 0.26 (95% CI −0.27 to 0.80). Changes from baseline did not differ significantly between groups on disease activity score (DAS) and C reactive protein.20 Authors contextualised that patients with active, recent-onset RA have high levels of adherence, in line with previous findings that patients with high disease activity tend to be more adherent than those with low disease activity,45 which may explain why their intervention did not show an effect. Hill et al’s19 intervention among patients with RA involved seven 30-min individual monthly consults covering information about RA medication and disease processes, pain control and coping strategies. Authors reported significant differences in adherence rates in the intervention and control groups (89% vs 55%; RR, 1.55; 95% CI 1.14 to 2.10).19 Among disease outcomes evaluated, authors reported an impact of the intervention on plasma viscosity.19 Evers et al evaluated the effect of individualised cognitivebehaviour therapy directly targeting frequently experienced problems in RA as well as indirectly, adherence. Authors reported that adherence in the intervention group increased at the
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Galo JS, et al. Ann Rheum Dis 2015;0:1–7. doi:10.1136/annrheumdis-2014-206593
RESULTS Search strategy We identified 2726 studies, forwarding 43 for full manuscript review after screening (figure 1). With exclusion of 22 manuscripts and inclusion of 2 after hand search of bibliographies, we identified 23 studies to satisfy our systematic review objectives.
Identification and classification of adherence interventions in rheumatic diseases
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Clinical and epidemiological research Figure 1 Systematic review study flow.
12 month follow-up assessment (t=−2.08, p14 years).38 Indeed, similar to the RCT by Rudd et al,43 modifying adherence in patients with a long disease duration may be harder to establish than forming new behaviour in recently diagnosed patients.43
Systemic lupus erythematosus In Ganachari and Almas’s37 RCT, the intervention group received three individualised counselling sessions from a clinical pharmacist while the control group received routine counselling from their physician. There was improved adherence in the intervention group compared with the control group (mean 5.8 vs 4.6); however no SDs or p values were reported.37 Ting et al28 evaluated daily text message reminders to patients with SLE in a two-part study. First, 70 patients received text message reminders for clinic visits and authors reported a decline in non-adherence to visits from 19% to 10% ( p=0.01). In the adherence intervention substudy where 41 patients were randomised to either text message reminders or usual care, there were no significant differences in adherence outcomes, which authors attributed to the novelty of the intervention wearing off due to its frequency.28
Juvenile idiopathic arthritis Rapoff et al35 evaluated a nurse-administered intervention involving one 30-min clinic visit involving a review and rehearsal of adherence enhancement strategies followed by a 12-month problem solving educational session. Authors reported significant differences in adherence as measured by Medication Event Monitoring Systems between the intervention and control groups (77.7±21.5 vs 56.9±33.0, p=0.02).35
DISCUSSION
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Clinical and epidemiological research comparison. Another recommendation is a requirement for studies to also incorporate disease outcomes, which was a limitation of many of the included studies in our systematic review as well as other reviews in other chronic diseases.21 Related to this is that follow-up times in included studies were relatively short (RCTs, mean 10 months; all studies mean 10.4 months). This may be particularly relevant to disease outcomes which may manifest over a longer term. Strengths and limitations of our systematic review deserve discussion. Applying a structured framework to classify interventions is a novelty of our systematic review that facilitated synthesis and allows the opportunity to inform the design of future interventions. Nonetheless, our systematic review may be vulnerable to publication bias. Consideration of a study that targeted an intervention to ‘patients with arthritis’ without explicit information on specific rheumatic diseases may also be a limitation,47 however we did not appraise this study as it was a RCT. Finally, due to the heterogeneity across interventions, adherence and disease outcomes, a quantitative meta-analysis was not performed. Overall, our systematic review shows limited research on adherence interventions in rheumatic diseases with inconsistent impacts on adherence or disease outcome. Given the substantial burden of treatment non-adherence across inflammatory arthritis, there is need for further work in designing and evaluating interventions that promote and support treatment adherence.
10
Correction notice This article has been corrected since it was published Online First. ‘Rheumatology arthritis’ has been corrected to ‘Rheumatoid arthritis (RA)’ in table 1.
21
Contributors JSG—Executed searches, extracted data, interpreted findings, drafted and revised manuscript; PM—interpreted findings, revised manuscript; SKR— interpreted findings, revised manuscript; AA-Z—interpreted findings, revised manuscript; MADV—Executed searches, extracted data, interpreted findings, drafted and revised manuscript. Funding MADV is a recipient of a Network Scholar Award from The Arthritis Society/Canadian Arthritis Network and a Scholar Award from the Michael Smith Foundation for Health Research. AA-Z is a recipient of a Scholar Award from the Michael Smith Foundation for Health Research and the BC Lupus Society. Competing interests None.
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Provenance and peer review Not commissioned; externally peer reviewed.
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Drugs Aging 2003;20:229–40. Gwadry-Sridhar FH, Manias E, Lal L, et al. Impact of interventions on medication adherence and blood pressure control in patients with essential hypertension: a systematic review by the ISPOR medication adherence and persistence special interest group. Value Health 2013;16:863–71. Williams JL, Walker RJ, Smalls BL, et al. Effective interventions to improve medication adherence in Type 2 diabetes: a systematic review. Diabetes Manag 2014;4:29–48. Nieuwlaat R, Wilczynski N, Navarro T, et al. Interventions for enhancing medication adherence (Review). Cochrane Database Syst Rev 2014;11:CD000011. Hill J, Bird H, Johnson S. Effect of patient education on adherence to drug treatment for rheumatoid arthritis: a randomised controlled trial. Ann Rheum Dis 2001;60:869–75. Brus HL, van de Laar MA, Taal E, et al. Effects of patient education on compliance with basic treatment regimens and health in recent onset active rheumatoid arthritis. Ann Rheum Dis 1998;57:146–51. Viswanathan M, Golin CE, Jones CD, et al. 4. Medication Adherence Interventions: Comparative Effectiveness Closing the Quality Gap: Revisiting the State of the Science. 2012. Report No.: 208. Roter DL, Hall JA, Merisca R, et al. Effectiveness of interventions to improve patient compliance—a meta-analysis. Med Care 1998;36:1138–61. The Consort Group. Consort 2010. http://www.consort-statement.org/consort-2010. Cohen J. Statistical power analysis for the behavioral sciences. 2nd edn. USA: Lawrence Erlbaum Associates, 1988. 567p. Bond CA, Monson R. Sustained improvement in drug documentation, compliance, and disease control. A four-year analysis of an ambulatory care model. Arch Intern Med 1984;144:1159–62. Lindroth Y, Bauman A, Barnes C, et al. A controlled evaluation of arthritis education. Br J Rheumatol 1989;28:7–12. Clifford S, Barber N, Elliott R, et al. Patient-centred advice is effective in improving adherence to medicines. Pharm World Sci 2006;28:165–70. Ting TV, Kudalkar D, Nelson S, et al. Usefulness of cellular text messaging for improving adherence among adolescents and young adults with systemic lupus erythematosus. J Rheumatol 2012;39:174–9. van den Bemt BJ, den Broeder AA, van den Hoogen FH, et al. Making the rheumatologist aware of patients’ non-adherence does not improve medication adherence in patients with rheumatoid arthritis. Scand J Rheumatol 2011;40:192–6. Berry D, Bradlow A, Bersellini E. Perceptions of the risks and benefits of medicines in patients with rheumatoid arthritis and other painful musculoskeletal conditions. Rheumatology 2004;43:901–5. El Miedany Y, El Gaafary M, El Arousy N, et al. Arthritis education: the integration of patient-reported outcome measures and patient self-management. Clin Exp Rheumatol 2012;30:899–904. Ravindran V, Jadhav R. The effect of rheumatoid arthritis disease education on adherence to medications and followup in Kerala, India: to the editor. J Rheumatol 2013;40:1460–1. Rees F, Jenkins W, Doherty M. Patients with gout adhere to curative treatment if informed appropriately: proof-of-concept observational study. Ann Rheum Dis 2013;72:826–30. Homer D, Nightingale P, Jobanputra P. Providing patients with information about disease-modifying anti-rheumatic drugs: Individually or in groups? A pilot randomized controlled trial comparing adherence and satisfaction. Musculoskelet 2009;7:78–92. Rapoff MA, Belmont J, Lindsley C, et al. Prevention of nonadherence to nonsteroidal anti-inflammatory medications for newly diagnosed patients with juvenile rheumatoid arthritis. Health Psychol 2002;21:620–3. Stockl KM, Shin JS, Lew HC, et al. Outcomes of a rheumatoid arthritis disease therapy management program focusing on medication adherence. J Manag Care Pharm 2010;16:593–604. Ganachari MS, Almas SA. Evaluation of clinical pharmacist mediated education and counselling of systemic lupus erythematosus patients in tertiary care hospital. Ind J Rheumatol 2012;7:7–12. 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Rudd RE, Blanch DC, Gall V, et al. A randomized controlled trial of an intervention to reduce low literacy barriers in inflammatory arthritis management. Patient Educ Couns 2009;75:334–9. Stinson JN, McGrath PJ, Hodnett ED, et al. An internet-based self-management program with telephone support for adolescents with arthritis: A pilot randomized controlled trial. J Rheumatol 2010;37:1944–52. Owen SG, Friesen WT, Roberts MS, et al. Determinants of compliance in rheumatoid arthritic patients assessed in their home environment. Br J Rheumatol 1985;24:313–20. Bender B, Milgrom H, Apter A. Adherence intervention research: what have we learned and what do we do next? J Allergy Clin Immunol 2003;112:489–94. Maisiak R, Koplon S, Heck LW. Subsequent behavior of users of an arthritis information telephone service. Arthritis Rheum 1990;33:212–18.
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What are the effects of medication adherence interventions in rheumatic diseases: a systematic review Jessica S Galo, Pavandeep Mehat, Sharan K Rai, Antonio Avina-Zubieta and Mary A De Vera Ann Rheum Dis published online February 9, 2015
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ARD Online First, published on February 13, 2015 as 10.1136/annrheumdis-2014-206593 Clinical and epidemiological research
EXTENDED REPORT
What are the effects of medication adherence interventions in rheumatic diseases: a systematic review Jessica S Galo,1 Pavandeep Mehat,1,2 Sharan K Rai,2,3 Antonio Avina-Zubieta,2,3,4 Mary A De Vera1,2 Handling editor Tore K Kvien ▸ Additional material is published online only. To view please visit the journal online (http://dx.doi.org/10.1136/ annrheumdis-2014-206593). 1
University of British Columbia Faculty of Pharmaceutical Sciences, Vancouver, British Columbia, Canada 2 Arthritis Research Canada, Richmond, British Columbia, Canada 3 Department of Experimental Medicine, University of British Columbia Faculty of Medicine, Vancouver, British Columbia, Canada 4 Division of Rheumatology, University of British Columbia Faculty of Medicine, Vancouver, British Columbia, Canada Correspondence to Dr Mary De Vera, University of British Columbia Faculty of Pharmaceutical Sciences, 2405 Wesbrook Mall, Vancouver, British Columbia, Canada V6T 1Z3; [email protected] Received 8 September 2014 Revised 13 January 2015 Accepted 15 January 2015
ABSTRACT Objectives Consistent reports of suboptimal treatment adherence among patients with inflammatory arthritis underscore the importance of understanding how adherence can be promoted and supported. Our objectives were to identify and classify adherence interventions; and assess the evidence on the effects of adherence interventions on outcomes of patients with rheumatic diseases. Methods We conducted a mapped search of Medline, Embase and International Pharmaceutical Abstract databases to identify studies meeting inclusion criteria of: (1) patient population with inflammatory arthritis; (2) evaluation of an intervention or programme targeting medication adherence directly or indirectly; (3) reporting of one or more measures of medication adherence and disease outcome; (4) publication in English, French or Spanish. For our first objective, we applied a structured framework to classify interventions according target ( patient vs provider), focus (educational vs behavioural vs affective), implementation (generalised vs tailored), complexity (single vs multifaceted) and provider. For the second objective, we appraised the evidence of effects of interventions on adherence and disease outcomes. Results We identified 23 studies reporting adherence interventions that directly or indirectly addressed treatment adherence in rheumatic diseases and further appraised included RCTs. Interventions that were shown to impact adherence outcomes were generally interventions directed at adherence, tailored to patients and delivered by a healthcare provider. For interventions that were not shown to have impacts, reasons may be those related to the intervention itself, patient characteristics or study methodology. Conclusions Our systematic review shows limited research on adherence interventions in rheumatic diseases with inconsistent impacts on adherence or disease outcome.
INTRODUCTION
To cite: Galo JS, Mehat P, Rai SK, et al. Ann Rheum Dis Published Online First: [please include Day Month Year] doi:10.1136/ annrheumdis-2014-206593
Adherence to long-term pharmacotherapy is paramount to the management of inflammatory arthritis —including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), gout and juvenile idiopathic arthritis ( JIA)—as left untreated, these conditions can result in disability, complications, morbidity and mortality.1–11 Yet systematic reviews have synthesised adherence rates as low as 10% in gout,12 30% in RA13 and 49% in SLE.14
While the problem of medication non-adherence is well described in rheumatology, solutions are not. Systematic reviews on adherence interventions in chronic disease including elderly15 patients with hypertension16 and diabetes17 are available, yet to our knowledge, there are none specifically among patients with rheumatic diseases. A 2014 update of a 2008 Cochrane review of adherence interventions increased included trials in RA from 219 20 to 6.18 However, an extension of this information is needed along with comprehensive knowledge of published evidence in patients with rheumatology. Thus, our objectives were to: (1) identify and classify adherence interventions; and (2) assess the evidence on the effects of adherence interventions on outcomes of patients with rheumatic diseases.
METHODS Literature search strategy We searched Medline (1946–June 2014), Embase (1974–June 2014) and International Pharmaceutical Abstracts (1970–June 2014). We used Medical Subject Headings for concepts underlying our search, ‘medication adherence’, ‘intervention’ and ‘inflammatory arthritis’ and applied keywords for concepts that did not map (see online supplementary table S1). We also conducted a hand search of bibliographies as well as a Google Scholar search.
Study selection Two authors reviewed all titles and abstracts to identify studies meeting the following inclusion criteria: (1) patient population with inflammatory arthritis (eg, RA, SLE, JIA); (2) evaluation of an intervention or programme targeting medication adherence directly or indirectly; (3) reporting of one or more measures of medication adherence and disease outcome; (4) publication in English, French or Spanish. As one of our objectives was to comprehensively identify instances where treatment adherence has been addressed in rheumatic disease, at this point, we did not exclude according to study design. Disagreement between reviewers was resolved by consensus.
Identification of adherence interventions in rheumatic diseases To address our first objective, we classified adherence interventions according to: (1) target (patient vs provider);21 (2) focus (educational vs behavioural vs affective);22 (3) complexity (single vs
Galo JS, et al. Ann Rheum Dis 2015;0:1–7. doi:10.1136/annrheumdis-2014-206593
1
Copyright Article author (or their employer) 2015. Produced by BMJ Publishing Group Ltd (& EULAR) under licence.
Downloaded from http://ard.bmj.com/ on March 10, 2015 - Published by group.bmj.com
Clinical and epidemiological research multifaceted);15(4) implementation (generalised vs tailored);15 and (5) provider (eg, physician, nurse, pharmacist) of the intervention. The target refers to the receiver of the intervention.21 The focus of the interventions were categorised as educational (designed to deliver information with a knowledge-based emphasis), behavioural (designed to change adherence by targeting behavioural patterns) or affective (designed to influence adherence through appeals to feelings or social relationships).22 The complexity of the intervention distinguishes ones that have a single focus from those with multiple foci.15 22 Implementation of the intervention may be categorised as tailored to patient or generalised.15 Finally, we specified the provider of the intervention.
Quality assessment of controlled trials of adherence interventions in rheumatic diseases To address our second objective of assessing the evidence on impacts of adherence interventions, we focused on included randomised controlled trials (RCTs). We developed a standardised quality assessment using the Consolidated Standards of Reporting Trials checklist.23 Studies were assessed for quality of the design, conduct and reporting, using the scoring criteria: 0=not done or reported, 0.5=partially done or reported and 1=well done and clearly reported (see online supplementary table S2).
Data extraction and outcome measurement We extracted information including study design, patient population, disease duration, sample size and medications. Our primary outcome was the effect of the intervention on adherence outcomes and we extracted information on whether this was reported or analysed, adherence measure, time point of measurement, value of adherence measure for the intervention and control group, and effect size. We calculated effect size where one was not reported. Specifically, for studies reporting mean values of the adherence measure, we calculated the standardised mean difference (SMD)—the difference of the group means divided by the standard deviation (SD) for the study group24 and for studies reporting adherence in terms of proportion of patients, we calculated the relative risk (RR)—the proportion of adherent patients in the intervention group divided by the proportion of adherent patients in the control group. Our secondary outcome was the effect of the intervention on disease outcomes and where possible, we similarly extracted information as with adherence outcomes. Due to heterogeneity and limited data availability, we could not perform similar calculations to estimate effect sizes for disease outcome measures.
directly target medication adherence, with all but one intervention29 directed at patients with rheumatology. This exception was an instrument providing rheumatologists with structured information about their patients’ non-adherence, which was not shown to have an impact on adherence or disease-related outcomes.29 With respect to focus, 21 interventions incorporated an educational component, one was a behavioural intervention involving text message reminders to patients with SLE,28 and the aforementioned rheumatologist-targeted intervention was classified as affective.29 Fourteen interventions were multifaceted and implementation was tailored to patients in 18 interventions. Interventions were delivered by rheumatologists,20 30–33 nurses,19 25 33–36 pharmacists,25 27 29 36–38 and other professionals including therapists39 and educators.40–44
Effects of adherence interventions in rheumatic diseases We critically appraised 13 RCTs—10 in RA, 2 in SLE and 1 in JIA. We did not include here a pilot RCT of group versus individual counselling for RA34 and a pilot RCT of internet-based self-management with telephone support for JIA.44 Quality scores varied from 9 to 28 out of a maximum possible score of 32 (mean=18.6; median=18.5). We ranked 719 20 27 38–40 43 as having good or high quality (above median) and 6 as having fair or poor quality. Key results of our synthesis are tabulated in table 1. Detailed information on adherence and disease outcomes are provided in online supplementary tables S4 and S5.
Rheumatoid arthritis
We classified adherence interventions described in 23 studies— 16 in RA, 3 in SLE, 1 in gout, 2 in JIA and 1 in unspecified arthritis. Study details along with intervention classifications are in online supplementary table S3. The description of interventions ranged from ‘one-on-one instruction’,25 ‘group education’,26 ‘telephone-based pharmacy advisory’,27 to ‘text message reminders’.28 Fourteen of 23 interventions were designed to
In McEvoy DeVellis et al’s42 study, all patients first participated in a psychosocial interview to assess problems related to their RA. The intervention group then received a problem-solving intervention to address problems identified in the interview.42 Authors cited no significant difference between groups, though did not report data.42 Authors also stated that all patients who participated in study, regardless of group assignment, improved on physical and psychological function measures, which may be attributed to unintended positive effects of the psychosocial interview received by both groups.42 Brus et al20 used group patient education meetings delivered by a rheumatologist four times over 1 month and subsequently at 4 months and 8 months for patients with recent-onset active RA. From reported mean adherence rates of 89±16 and 84±21 in the intervention and control groups, respectively, we estimated a SMD of 0.26 (95% CI −0.27 to 0.80). Changes from baseline did not differ significantly between groups on disease activity score (DAS) and C reactive protein.20 Authors contextualised that patients with active, recent-onset RA have high levels of adherence, in line with previous findings that patients with high disease activity tend to be more adherent than those with low disease activity,45 which may explain why their intervention did not show an effect. Hill et al’s19 intervention among patients with RA involved seven 30-min individual monthly consults covering information about RA medication and disease processes, pain control and coping strategies. Authors reported significant differences in adherence rates in the intervention and control groups (89% vs 55%; RR, 1.55; 95% CI 1.14 to 2.10).19 Among disease outcomes evaluated, authors reported an impact of the intervention on plasma viscosity.19 Evers et al evaluated the effect of individualised cognitivebehaviour therapy directly targeting frequently experienced problems in RA as well as indirectly, adherence. Authors reported that adherence in the intervention group increased at the
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RESULTS Search strategy We identified 2726 studies, forwarding 43 for full manuscript review after screening (figure 1). With exclusion of 22 manuscripts and inclusion of 2 after hand search of bibliographies, we identified 23 studies to satisfy our systematic review objectives.
Identification and classification of adherence interventions in rheumatic diseases
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Clinical and epidemiological research Figure 1 Systematic review study flow.
12 month follow-up assessment (t=−2.08, p14 years).38 Indeed, similar to the RCT by Rudd et al,43 modifying adherence in patients with a long disease duration may be harder to establish than forming new behaviour in recently diagnosed patients.43
Systemic lupus erythematosus In Ganachari and Almas’s37 RCT, the intervention group received three individualised counselling sessions from a clinical pharmacist while the control group received routine counselling from their physician. There was improved adherence in the intervention group compared with the control group (mean 5.8 vs 4.6); however no SDs or p values were reported.37 Ting et al28 evaluated daily text message reminders to patients with SLE in a two-part study. First, 70 patients received text message reminders for clinic visits and authors reported a decline in non-adherence to visits from 19% to 10% ( p=0.01). In the adherence intervention substudy where 41 patients were randomised to either text message reminders or usual care, there were no significant differences in adherence outcomes, which authors attributed to the novelty of the intervention wearing off due to its frequency.28
Juvenile idiopathic arthritis Rapoff et al35 evaluated a nurse-administered intervention involving one 30-min clinic visit involving a review and rehearsal of adherence enhancement strategies followed by a 12-month problem solving educational session. Authors reported significant differences in adherence as measured by Medication Event Monitoring Systems between the intervention and control groups (77.7±21.5 vs 56.9±33.0, p=0.02).35
DISCUSSION
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Clinical and epidemiological research comparison. Another recommendation is a requirement for studies to also incorporate disease outcomes, which was a limitation of many of the included studies in our systematic review as well as other reviews in other chronic diseases.21 Related to this is that follow-up times in included studies were relatively short (RCTs, mean 10 months; all studies mean 10.4 months). This may be particularly relevant to disease outcomes which may manifest over a longer term. Strengths and limitations of our systematic review deserve discussion. Applying a structured framework to classify interventions is a novelty of our systematic review that facilitated synthesis and allows the opportunity to inform the design of future interventions. Nonetheless, our systematic review may be vulnerable to publication bias. Consideration of a study that targeted an intervention to ‘patients with arthritis’ without explicit information on specific rheumatic diseases may also be a limitation,47 however we did not appraise this study as it was a RCT. Finally, due to the heterogeneity across interventions, adherence and disease outcomes, a quantitative meta-analysis was not performed. Overall, our systematic review shows limited research on adherence interventions in rheumatic diseases with inconsistent impacts on adherence or disease outcome. Given the substantial burden of treatment non-adherence across inflammatory arthritis, there is need for further work in designing and evaluating interventions that promote and support treatment adherence.
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Correction notice This article has been corrected since it was published Online First. ‘Rheumatology arthritis’ has been corrected to ‘Rheumatoid arthritis (RA)’ in table 1.
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Contributors JSG—Executed searches, extracted data, interpreted findings, drafted and revised manuscript; PM—interpreted findings, revised manuscript; SKR— interpreted findings, revised manuscript; AA-Z—interpreted findings, revised manuscript; MADV—Executed searches, extracted data, interpreted findings, drafted and revised manuscript. Funding MADV is a recipient of a Network Scholar Award from The Arthritis Society/Canadian Arthritis Network and a Scholar Award from the Michael Smith Foundation for Health Research. AA-Z is a recipient of a Scholar Award from the Michael Smith Foundation for Health Research and the BC Lupus Society. Competing interests None.
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Provenance and peer review Not commissioned; externally peer reviewed.
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What are the effects of medication adherence interventions in rheumatic diseases: a systematic review Jessica S Galo, Pavandeep Mehat, Sharan K Rai, Antonio Avina-Zubieta and Mary A De Vera Ann Rheum Dis published online February 9, 2015
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