Review article: medication non-adherence in ulcerative colitis – strategies to improve adherence with mesalazine and other maintenance therapies


Dr A. B. Hawthorne, Department of Medicine, University Hospital of Wales, Heath Park, Cardiff CF14 4XW, UK.


Background  Significant number of patients with ulcerative colitis (UC) fail to comply with treatment.

Aims  To review issues surrounding medication non-adherence in inflammatory bowel disease (IBD), including the clinical and health service implications in the UK, and discuss strategies for optimizing medication adherence.

Methods  Articles cited were identified via a PubMed search, utilizing the words IBD, adherence, compliance, medication and UC.

Results  Medication non-adherence is multifactorial involving factors other than dosing frequency. Male gender (OR: 2.06), new patient status (OR: 2.14), work and travel pressures (OR: 4.9) and shorter disease duration (OR: 2.1), among others are proven predictors of non-adherence in UC. These indicators can identify ‘at-risk’ patients and allow an individually tailored treatment approach to be introduced that optimizes medication adherence. A collaborative relationship between physician and patient is important; several strategies for improving adherence have been proven effective including open dialogue that takes into consideration the patient’s health beliefs and concerns, providing educational (e.g. verbal/written information, self-management programmes) and behavioural interventions (e.g. calendar blister packs, cues/reminders).

Conclusions  Educational and behavioural interventions tailored to individual patients can optimize medication adherence. Additional studies combining educational and behavioural interventions may provide further strategies for improving medication adherence rates in UC.


The nature of ulcerative colitis (UC) dictates that therapy should be continued indefinitely in most patients. Treatment with 5-aminosalicylates (5-ASAs) is effective in inducing and maintaining remission in UC patients,1, 2 and is associated with a reduced risk of developing colorectal cancer (CRC) in the long term.3, 4 As with other chronic conditions, however, medication non-adherence in patients with UC is common. This review describes the extent of the problem, its clinical and health service implications in the UK, and considers the evidence for strategies to optimize medication adherence in UC.

Extent of the problem

‘Compliance’ and ‘adherence’ are terms used synonymously to describe the extent to which patients follow the advice of healthcare professionals regarding their medication and disease management. Non-adherence describes the failure to take medication as intended by the physician and can be intentional or unintentional. Patients with chronic diseases may fail to comply with long-term therapies or clinicians’ recommendations. This has been demonstrated for, amongst others, patients with hypertension5, 6 and diabetes.7 Within the controlled environment of clinical trials, where there is a high presence of medical supervision, approximately 70–95% of patients with inflammatory bowel disease (IBD) adhere to their medication.8–10 However, this high rate of medication adherence is not reflected in normal clinical practice. A cross-sectional study of US outpatients with quiescent UC found that only 40% were adherent to maintenance mesalazine (mesalamine) therapy.8

Several community-based studies have reported non-adherence rates ranging from 43% to 72% of IBD patients.8, 11–14 In the UK, approximately 15% of patients fail to even redeem prescriptions at the pharmacist.15

Treatment non-adherence rates vary considerably between countries. Within Europe, a survey of 203 IBD patients revealed self-reported non-adherence rates ranging from 13% in France, to 26% in Italy, 33% in UK and 46% in Germany; with an overall non-adherence rate of 29% across Europe.16

Detecting medication non-adherence

Direct enquiry can detect most, but not all non-adherent patients. In a study of 98 IBD patients, self-reporting correctly identified 66% of patients that were non-adherent, as assessed by urinary drug measurements of 5-ASA.14 Urinary salicylate levels correlate positively with urinary 5-ASA levels, and its measurement has become the standard test in most UK hospitals, representing a simple method for assessing adherence to 5-ASA therapy.17 Other methods of ascertaining levels of medication non-adherence include asking family members, checking prescription uptake at the pharmacist or asking patients to bring their tablets to consultations.17

Clinical implications of medication non-adherence

Increased risk of relapse

In UC, failure to take 5-ASA therapy increases the risk of relapse,18 which in turn impacts on health-related quality of life measures.19 A cohort study of 99 quiescent UC patients demonstrated that patients who were non-adherent to their prescribed 5-ASA therapy had a greater than fivefold increased risk of clinical relapse.18 Moreover, adherent patients were shown to have an 89% chance of maintaining remission, compared with only 39% in non-adherent patients.18

Increased risk of developing CRC

The risk of developing CRC increases with the extent and duration of UC, and is associated with a life-time risk of approximately 20%.20 Case-control studies have shown that the regular use of 5-ASA therapy significantly reduces the risk of developing CRC by up to 75% in UC patients in the long term.3, 21 A 10-year cohort study demonstrated that 31% of UC patients who had stopped 5-ASA therapy, or who did not comply with treatment, had developed CRC compared with only 3% who continued with long-term treatment.22 Furthermore, a systematic review and meta-analysis of observational studies confirmed the protective role of 5-ASA use against CRC development.4

Increased healthcare costs

In the UK, a single centre retrospective study of IBD patients showed individual patient costs ranged from £73 to £33 254, with a mean 6-month cost of £1256 (95% CI: £988, £1721) per UC patient.23 The high percentage of non-adherent patients who are at an increased risk of relapse is likely to contribute to the overall high costs associated with the treatment of UC. Indeed, disease relapse was associated with a two- to threefold increase in costs for non-hospitalized cases and a 20-fold increase in costs for hospitalized cases compared with quiescent cases of IBD.23

Healthcare system implications in the UK

An estimated 100 000 people in the UK are affected with UC and incidence rates of 11 cases per 100 000 person-years have been reported.24 In the UK, UC is managed mainly in secondary care, and as a direct consequence of a Government target known as the ‘two-week wait’ for CRC, an increasing number of colorectal surgeons and not gastroenterologists are the first specialists to diagnose IBD patients in the clinic. Regular outpatient reviews are carried out by specialist clinicians and supported by IBD nurse specialists.

General practitioners (GPs) rarely make the definitive diagnosis or initiate treatment, but they do contribute significantly to meeting the healthcare needs of patients, and generally continue treatment under the guidance of a specialist. Therefore, in the UK, the facilitation and monitoring of medication adherence in UC involves a multidisciplinary team, including gastroenterologists, consultant colorectal surgeons, IBD nurse specialists and GPs.25 An increasing emphasis on ‘efficiency’ in out-patient clinics in the NHS, by increasing the new/follow-up ratio, and thus encouraging fewer follow-up appointments each year, will reduce the opportunity for physicians to interact with patients and monitor their compliance.

Predictors of medication non-adherence

A number of factors are associated with non-adherence in UC (Table 1). Non-adherent patients are statistically more likely to be male (67% vs. 52% in adherent patients, respectively), single (86% vs. 53%), have left-sided disease (vs. pancolitis) (83% vs. 51%), or be taking four or more concomitant medications (60% vs. 40%).8 Other factors, such as the approach/attitude of the physician, the perceptions/beliefs of patients, side effects, prescription costs and illness-related factors (i.e. the reduction/absence of symptoms) have also been linked to non-adherence.26 Shale and Riley’s study14 demonstrated that three times daily dosing and full-time employment were independent predictors of partial non-adherence in patients taking delayed-release mesalazine, whereas depression was an independent predictor of complete non-adherence. In addition, new patient status, shorter disease duration, younger age, patient discordance and work/travel pressures are also good predictors of non-adherence (Tables 1 and 2).27, 28

Table 1.   Predictive factors of non-adherence in ulcerative colitis10, 14, 27, 28 and strategies to optimize adherence
Predictive factorsExamples of strategies to optimize adherence
Male gender
Single status
Younger age
Full-time employment
Identify these ‘at-risk’ group of patients and communicate risks of medication non-adherence, e.g. via patient information packs, etc.
Three times daily dosing
Four or more concomitant medications
Address dosing regimen
Suggest medication taking cues, e.g. alarm clocks, placing tablets near toothpaste, etc.
Raise patient education/awareness, e.g. chemoprevention
New patient status
Left-sided disease
Arrange regular follow-up appointments
Maximize time for consultation
Sign-posting to patient support groups/services, patient website/chat-rooms
Fully utilize IBD nurses
Patient discordanceOpen communication with patients, e.g. open questions, appropriate tone and language
Disease durationPeriodic enforcement of educational information
Table 2.   Effects of different parameters/factors on medication non-adherence rates (%)
 Kane et al.8Shale and Riley14Bernal et al.12Cervenýet al.29 D’Inca et al.28
  1. IDC, indeterminate colitis; 5-ASA, 5-aminosalicylate; IBD, inflammatory bowel disease; UC, ulcerative colitis; ns, not significant between adherent and non-adherent patients, specific data not published; na, not associated with non-adherence; –, specific data not reported or parameter not investigated.

Number of IBD patients; UC vs. CDn = 94; 94 UC, 0 CDn = 98; 62 UC, 26 CD (10 IDC)n = 214; 99 UC, 115 CDn = 177; 60 UC, 117 CDn = 485; 265 UC, 218 CD
Male67%; P < 0.05 vs. female; OR: 2.0642%; ns vs. female
Female (%)5235
Younger ageP < 0.05; adherent vs. non-adherent patients
<40 years43%; P = 0.041 vs. ≥40 years; OR:1.5
≥40 years34%
Marital statusns
Single68%; P = 0.04 vs. married
Employment statusns
Full-time employment62%; OR: 2.7
No. of drugs prescribedns
≥4 prescriptions68%; P < 0.05 vs. <4 prescriptions; OR: 2.5
<4 prescriptions40%
Disease type*/severity*ns
Left-sided disease83%; P < 0.01 vs. pancolitis
Less-extensive disease–; P = 0.04 vs. extensive disease
Patients in remission26.1%
Chronically active45.1%
Patients with flare66.6%
Disease duration
<5 years24%;P < 0.005, vs. ≥5 years; OR:2.1
≥5 years15%
>10 years40%
Treatment type†/length †ns
Oral mesalazine71.5–90.5%
Topical treatment13%
Topical therapy with enemas68%; P = 0.001 vs. oral therapy; OR: 0.25
Oral therapy 40%
Topical steroids45%
Systemic steroids40%
≤10 years treatment37.5%
Other factors
No. of daily dosens
TDS regimen57%; P < 0.05 adherent vs. non-adherent patients; OR: 3.1
Patient busy at work/travels often30%; P < 0.0005, vs. patients at home; OR: 4.9
Patient at home6%

Many patients with IBD deliberately decide not to continue with treatment.13, 27, 29 As one Spanish study in 40 IBD patients has shown, up to 35% of patients are intentionally non-adherent compared with 67% who are unintentionally non-adherent.13 A greater association was found between intentional non-adherence and patients who had high depression scores and high patient–physician discordance, patients with long-standing IBD, patients who did not consider themselves to be adequately informed about their treatment and patients who trusted their treating physicians less.13

The main reasons given by IBD patients for non-adherence to medication are forgetfulness, disbelief in the need for so much medicine, disease denial and lack of perceived benefits of treatment during symptom-free periods (Table 3).18, 26, 28 Correction of the factors (modifiers) associated with poor adherence, both intentional and unintentional, and addressing patient concerns and beliefs, could therefore result in greater therapeutic success.13

Table 3.   Patients’ reasons for non-adherence (adapted from Kane10)
 Disease denial
 Lack of perceived benefit of treatment
 Poor interactional style
 Insufficient support/information
 Complicated drug regimen, i.e. number of tables/frequency
 Side effects or fear of side effects
 Cost of prescription

Strategies to optimize adherence in UC

Collaboration in partnership

A large body of evidence supports the key role of the physician–patient relationship in achieving higher patient medication-adherence rates.30–32 Health outcomes of common symptoms were greatly improved when physicians and patients collaborated in partnership to reach agreement about the nature of the problem underlying the symptoms.33 Indeed, the physician’s willingness to allow patients to contribute input during the initial medical visit was suggested to facilitate treatment decisions that are meaningful to both parties.34

Non-adherence is more common among patients who report a lack of confidence in their physician’s ability to help, or a lack of satisfaction with the concern shown by their physician.32 A waiting room survey of 370 patients showed that trust in the physician and continuity of care by the same doctor were also important to patients.35 Patients who reported high levels of concordance with their physician, as determined by a series of questions evaluating the extent of agreement between the physician and patient, were 33% more likely to adhere to their treatment.35 This supports the findings reported in a Canadian prospective study of IBD patients, which showed a direct correlation between patient–physician discordance and non-adherence.27

Consultation style.  The consultation style adopted by the physician is also an important factor in building the physician–patient relationship. The adoption of a ‘paternalistic’ approach, i.e. giving orders and assuming a more authoritative, controlling manner is counter productive, and the patient is less likely to participate in discussions or follow advice.36 Indeed, when physicians exhibited less control dominance, a reported increase in patient adherence and satisfaction was observed.37

The most effective approach for improving medication adherence is to encourage more open, co-operative relationships that lead to concordance between the physician and patient.38 In addition, to ensure that the co-operative approach is successful, physicians should ascertain a patient’s ability to make decisions, empathize with their needs and concerns, and involve them in the treatment decision-making process.38 During consultations, all factors affecting adherence need to be explored, including the patient’s level of knowledge, belief systems and support environment, e.g. network of family and friends (Figure 1).

Figure 1.

 Factors influencing medication-related behaviour (adapted from Hall et al.42) illustrating the factors affecting the balance between fears and concerns, and acceptance of medication.

Understanding patient health beliefs in UC.  Among the various factors associated with adherence behaviour, understanding patients’ health beliefs is key to improve adherence.39 Many patients are ambivalent to, or have negative views of treatment and are reluctant to discuss this with their physician. Patients weigh up their beliefs for the necessity of treatment against the potential of adverse effects, and this influences their adherence behaviour.40

Despite considerable research investigating the impact of patient health beliefs on attitudes to illness and adherence, few publications are available that relate specifically to IBD. One study by Hall et al.,41 who conducted a study in 31 patients with IBD (17 of whom had UC), examined the effects of health beliefs on treatment behaviour using semi-structured interviews and focus groups. Patients’ attitudes and beliefs towards medication were found to be based on an ongoing balance between three main areas: (i) acceptance and perceived necessity of medication, (ii) fears and concerns and (iii) the perceived impact of IBD and its symptoms. The relative influence of these three areas changes continuously and the balance between them affects medication taking behaviour, self-management and healthcare seeking behaviour.42 The patient’s relationship with their physician, the patient's knowledge and experience of the disease and its treatment, and their ability to accept the need for treatment influences this balance, which in turn affects patients’ overall perceptions of their illness.42 These concepts are illustrated in Figure 1.

Educational interventions

In chronic conditions, adherence can be improved by using educational interventions, including written and verbal communication.43–45 Education may also be beneficial to partners, carers, family and friends, as they play an important role in supporting patients and encouraging adherence.45, 46

Written and verbal communication.  Written and oral education has been shown to increase adherence by approximately 6–25%.47 Written information is more effective when reinforced verbally. Robinson et al.48 studied the effect of a structured education programme on patient adherence that used both written and verbal information. Patients who received written information with verbal reinforcement were significantly more likely to adhere to therapy than those receiving written information alone.48 In addition, a study of 69 patients with IBD demonstrated an improved knowledge, patient satisfaction and a positive trend towards greater adherence in patients who had undertaken the IBD education programme (consisting of pamphlets and ad hoc physician education) compared with patients who received standard care.49

Self-management.  Randomized, controlled studies evaluating guided self-management programmes in patients with IBD have demonstrated an acceleration of treatment provision, a reduction in hospital visits, without an increase in morbidity and greater confidence in the patient’s ability to cope with IBD.50, 51 In addition, adoption of self-management strategies for IBD in the UK is likely to reduce healthcare costs without having any adverse effects on patient health outcomes.52 Furthermore, guided self-management educational programmes that involve the development of shared guidelines agreed by the physician and patient could have a positive impact on medication adherence, but this remains to be further evaluated.53

Behavioural interventions

The use of behavioural interventions such as dosage simplification, treatment cues/reminders, charts and pill containers may help to improve adherence to long-term medications.43, 54 Greater treatment adherence rates are associated with less frequent dosing regimens.47, 55, 56 In a study involving 105 hypertensive patients receiving long-term treatment, once daily (o.d.) or twice daily (b.d.) dosing was associated with significant improvements in mean adherence rates compared with three times daily (t.d.s.) dosing (96%, 93% and 83.8%, respectively; P < 0.05), with no statistical significance between o.d. and b.d. dosing.56

A literature review reported significantly better medication adherence rates with o.d. and b.d. dosing (i.e. 73% and 70%, respectively) than t.d.s. (52%), or four times daily dosing (q.d.s.; 42%) regimens.57 Similarly, another systematic review of studies evaluating the effect of dosing frequency on adherence showed that adherence was significantly greater with o.d. and b.d. dosing than t.d.s. or q.d.s.55 However, although o.d. was significantly better than t.d.s. or q.d.s., there was no significant difference in adherence between o.d. and b.d. dosing. The reasons are possibly statistical as the increment in adherence is smaller between b.d. and o.d. dosing.55

In a randomized trial of maintenance therapy with mesalazine granules 2 g/day in 362 patients, the remission rate after 1 year was significantly higher (74%) in the group given a single daily dose of 2 g, compared to those given 1 g b.d. (64%; P = 0.024). There was evidence from patient questionnaires that adherence was better in the o.d. group, and this may in part explain the unexpected difference, as the trial was designed to show non-inferiority of the o.d. regimen.58

Several studies have examined the effect of various interventions on medication adherence, but as yet, there are no studies that relate specifically to IBD patients. Therefore, drawing from evidence-based examples, the use of adherence aids and reminders has been shown to be useful for improving medication adherence to antihypertensive or lipid-lowering medication.59 A review of the literature showed that the introduction of adherence aids and refill or follow-up reminders increased adherence by 6–25%.47 In addition, adherence as determined by prescription refills was significantly increased in patients receiving a computer-generated postcard or telephone reminder.60

A number of more high-tech aids including email reminders, text messaging and electronic pill dispensers are now available, and studies are underway to establish the effectiveness of these devices. Nevertheless, combining education and behavioural interventions has been suggested to be the most effective approach to improving adherence.43


In the UK, a significant percentage of UC patients are non-adherent to their prescribed medication. Medication non-adherence is multifactorial and correction or modification of these factors can lead to significant benefits, from both personal and economic standpoints.

The physician–patient relationship impacts tremendously on adherence and as such, an open, co-operative relationship that involves patients in the treatment decision-making process, and deciphering of patients’ health beliefs and their concerns is most beneficial. Several educational (e.g. verbal and written, and self-management initiatives) as well as behavioural (e.g. dosage simplification, calendar blister packs, cues and reminders) interventions have been shown to improve adherence.

However, a combination of educational and behavioural strategies tailored to individual patients may be the most effective way of optimizing medication adherence. Intervention studies are needed to establish the impact of interventions and combinations of interventions (e.g. self-management programmes, education programmes, patient support programmes and cues/reminders) on medication non-adherence, and how interventions can be tailored to individual patients. UC patients most at risk of medication non-adherence can be identified, and targeting these individuals with specific interventions will give the most benefit in improved patient outcomes.


The authors acknowledge the contributions of Dr Quyen Chu (a member of the European Medical Writer’s Association) for her professional medical writing and editorial support. Declaration of personal interests: AB Hawthorne has served as a speaker, a consultant and an advisory board member for Procter & Gamble, Schering Plough, Shire and Ferring Pharmaceuticals Ltd. GP Rubin has provided advice to Shire and Procter & Gamble Pharmaceuticals Ltd. S Ghosh has spoken at educational meetings supported by Schering Plough, Centocor, Abbott, UCB, Procter & Gamble Pharmaceuticals, Ferring and Falk Pharma, and advised Schering Plough, Centocor, Abbott, UCB, Procter & Gamble Pharmaceuticals, Shire and Falk Pharma. Declaration of funding interests: The authors acknowledge the funding for professional writing services from Procter & Gamble Pharmaceuticals Ltd. AB Hawthorne received research funding from Procter & Gamble Pharmaceuticals Ltd. GP Rubin has received speaker’s fees from Ferring Pharmaceuticals.