SciELO - Scientific Electronic Library Online

 
vol.44 número2Consenso para identificar los riesgos de los medicamentos peligrosos en los servicios de farmacia hospitalariaTerapias modificadoras de la enfermedad en esclerosis múltiple: revisión sistemática de costo-efectividad índice de autoresíndice de materiabúsqueda de artículos
Home Pagelista alfabética de revistas  

Servicios Personalizados

Revista

Articulo

Indicadores

Links relacionados

  • En proceso de indezaciónCitado por Google
  • No hay articulos similaresSimilares en SciELO
  • En proceso de indezaciónSimilares en Google

Compartir


Farmacia Hospitalaria

versión On-line ISSN 2171-8695versión impresa ISSN 1130-6343

Farm Hosp. vol.44 no.2 Toledo mar./abr. 2020  Epub 28-Sep-2020

http://dx.doi.org/10.7399/fh.11325 

Originals

Adherence to treatment with adalimumab, golimumab and ustekinumab in patients with inflammatory bowel disease

María Calvo-Arbeloa1  , Ana María Insaustl-Serrano2  , Amaya Arrondo-Velasco1  , María Teresa Sarobe-Carricas1 

1Pharmacy Department, Complejo Hospitalario de Navarra, Pamplona. Spain.

2School of Health Sciences, Universidad Pública de Navarra, Tudela. Spain.

Abstract

Objective:

Inflammatory bowel disease comprises a group of chronic relapsing inflammatory disorders affecting the bowel. In the last decade, the advent of biological drugs brought about a drastic change in the treatment of the disease. Adalimumab, golimumab and ustekinumab are three biologic agents that patients can self-administer subcutaneously after collecting them from the pharmacy department. However, for the treatment to be effective, adherence is paramount. The purpose of the present study is to evaluate adherence in patients who collected all three drugs from the dispensary of a tertiary care hospital.

Method:

A cross-sectional observational analysis was carried out of patients who had been receiving treatment with adalimumab, golimumab and ustekinumab for at least four months. The medication possession ratio was calculated based on information extracted from the pharmacy dispensing records. Patients with a ratio < 85% were enrolled in the study and asked to respond to Morisky-Green Medication Adherence Questionnaire.

Results:

One-hundred and seventy-eight patients were included, of whom 60.1% (107) were male and 30.9% (55) had been treated pre viously with other biologics. According to the pharmacy dispensing re cords, mean adherence was 91.79%, with 45 patients (25.28%) classified as scarcely compliant (< 85%). The Morisky-Green Medication Adherence Questionnaire revealed that carelessness about administering the drug at the right time and forgetfulness were the main reasons for therapeutic non-adherence. Female sex (odds ratio 0.42; p = 0.013) and lengthy treatments (p = 0.002) were associated to lower adherence rates.

Conclusions:

Although most patients in the studied population were seen to be compliant, low levels of adherence were observed in a number of patients who would benefit from interventions aimed at boosting their adherence. It must be said, however, that the statistical power of this study should be enhanced in order to increase the significance of the results obtained.

KEYWORDS: Therapeutic adherence; Biological therapy; Adalimumab; Golimumab; Ustekinumab; Inflammatory bowel disease

Introduction

Inflammatory bowel disease (IBD) comprises a group of chronic relap sing inflammatory conditions mainly affecting the bowel. Such conditions are Crohn's disease (CD), ulcerative colitis (UC) and indeterminate colitis (IC)1. Although these conditions have of late shown an increasing incidence, efforts to determine their etiology have so far been fruitless2,3.

As regards clinical management, fecal calprotectin (FC) is a biomarker that makes it possible to accurately identify the presence of mucosal lesions and correlate the extent of mucosal damage to the response to the treatment applied4.

The goals of treatment in patients with IBD include inflammation suppres sion, mucosal healing and symptom remission. To achieve them, clinicians can avail themselves of two classes of drugs: biologics and non-biologics (aminosalicylates, corticosteroids, antibiotics, immunomodulators, prebiotics and probiotics)5.

The former class of drugs heralded an about-face in the therapeutic ap proach to IBD. Currently approved drugs in this category include infliximab, vedolizumab, adalimumab, golimumab (only for UC) and ustekinumab (only for CD). These agents modulate inflammation, inducing and maintaining the clinical response6. According to GETECU (Spanish Working Group on CD and UC), first-line treatment in patients with these conditions should be based on conventional (non-biologic) drugs, with biologics to be reserved for patients who fail conventional agents. The exception to this rule would be patients with an aggressive onset, where biologics could be used as first-line treatment7,8.

For a drug to be optimally effective, good therapeutic adherence is of the essence. The World Health Organization (WHO), defines adherence as the extent to which a person's behavior (taking medication, following a diet and/or executing lifestyle changes) corresponds with agreed recom mendations from a healthcare provider.

A concept that is akin yet different from adherence is persistence, which is defined as the length of time over which treatment is maintained9.

According to a systematic review carried out in 2013 by López et al., adherence to adalimumab and infliximab is highly variable, ranging from 36.8 to 96%10.

Poor therapeutic adherence could result in the loss of clinical response and a higher risk of developing adverse reactions, which tend to impair the patients' quality of life and increase the healthcare bill11.

An understanding of the factors that may potentially influence treatment adherence could help identify patients likely to be poor adherents so that more attention can be focused on them. These factors can be classified into 4 categories: demographic (sex, age...); clinical (IBD type, age at diagnosis...); treatment-related (type of drug, administration route...); and psychosocial (quality of life, perception of the disease.)12.

Several methods have been developed to measure adherence in pa tients with chronic conditions. The most common ones are those based on questionnaires and those based on pharmacy dispensing records.

As regards questionnaires, the most commonly used validated question naires to determine adherence in patients with IBP are the following: the Morisky-Green Medication Adherence Questionnaire (MAQ)13; the Visual Analog Scale (VAS); the Forget Medicine Scale14; and the 5-Medication Adherence Report Scale (MARS-5)15, commonly used to determine adhe rence in patients with chronic conditions. The 8-item Morisky Medication Adherence Scale, an IBD-specific scale developed based on the MAQ questionnaire, was also used16.

The medication possession ratio (MPR) is an easy-to-calculate low-cost tool to determine adherence to a given medication. In the case of anti-TNF agents, it has been shown that an MPR < 80% is associated with a loss of response, which results in a poorer prognosis17.

According to the literature, the most accurate estimation of treatment adherence is usually obtained by combining two methods such as MPR and self-administered questionnaires18.

The overarching goal of the present study was to use the MPR score to determine adherence to treatment with adalimumab, golimumab and uste kinumab in patients afflicted with IBD who obtained such agents from the pharmacy dispensary of a tertiary care hospital.

Secondary endpoints included a comparison of the adherence ra tes obtained using the MAQ questionnaire and the MPR scale (in the subgroup of patients where adherence was < 85%); an identification of factors responsible for non-adherence; an analysis of the relationship between adherence and effectiveness of treatment (according to the FC levels present) in patients with adherence < 85%; and, lastly, an evalua tion of persistence and the reasons why previous treatments with biologic agents were discontinued.

Methods

Between January and June 2019. a cross-sectional observational analy sis was carried out to determine adherence to treatment drawing upon data obtained from the dispensation records of the pharmacy department of a tertiary care hospital. Potential causes of non-adherence were analyzed based on the answers to the MAQ questionnaire given by the subgroup of patients exhibiting adherence 85% according to the pharmacy dispensing records.

Inclusion criteria were as follows: patients had to be older than 18 years; they were required to have been diagnosed with either CD or UC; and they had to have been on adalimumab, golimumab or ustekinumab for four months or longer. They were also required to have a MPR < 85%. Indeed, although most studies use an 80% threshold10, a decision was made to establish an 85% cutoff in order to enhance the statistical power of the results. Patients with disabling mental illness were excluded.

The variables recorded for the whole patient population were so ciodemographic (age, sex) and clinical (type of treatment, length of treatment, previous use of other biologics and use of concomitant drugs). In the poor adherence group the variables analyzed fell into two groups: sociodemographic variables (weight, height, smoking status, educatio nal status and occupational status) and clinical variables (diagnosis, age at diagnosis, duration of the disease (in months), reason for discontinua tion of other biologics, MAQ questionnaire results, discontinuation of treatment, hospital admissions, infections requiring deferral of treatment; and FC levels).

The MPR rate was calculated using data from the pharmacy dispen sing records corresponding to the previous 4 months. The formula is as follows:

TPM = ((nr of units dispensed - nr of units returned) /

(nr. of units prescribed)) x 100

MAQ is a standardized self-administered questionnaire designed to measure therapeutic adherence on the basis of four yes/no questions that the patient must answer13.

The analysis also investigated whether patients had received any pre vious biological treatment, the reasons for discontinuing it and their persis tence, which was calculated as the length of treatment from the initial to the last prescription issued.

The SSPS 25.0 software package was used for the statistical analy sis. An initial analysis was made of the whole patient population, which was followed by a second analysis that only included the low-adherence subgroup. First of all, an univariate analysis was performed. Differences between continuous variables were calculated using either Student's t-test or its nonparametric equivalent to identify differences between continuous variables (depending on normality). The chi-squared test was used for cate gorical variables. Significant variables (p < 0.05) were included in a logistic regression model.

Prior to filling in the questionnaire, the low adherence patients inclu ded in the study (n = 32) were required to sign an informed consent form granting the research team access to their clinical records. The study was authorized by the relevant Ethical Committee.

Results

Figure 1 provides details on patient adherence to the different types of treatment. Firstly, the pharmacy dispensation records for the 178 patients who met the inclusion criteria were used to determine their adherence to treatment over the previous four months. The records revealed that 45 of those patients exhibited an adherence rate < 85%. Of those 45 patients, only 32 were eventually included in the study.

Figure 1. Overview of the study cohort. 

Of the 13 patients who were not included, 6 had discontinued their treatment, 1 had to be admitted for acute leukemia, 4 did not show up to collect their medication, and another 2 patients refused to participate.

Of the total sample, 107 (60.10%) subjects were male, with a mean age of 46.08 (14.86) years. Of them 136 (76.40%) were treated with adalimumab, 15 (8.42%) with golimumab and 27 (15.16%) with ustekinumab. Mean duration of treatment was 135.18 (93.33) weeks. Forty-six patients (25.80%) received concomitant treatment with mesalamine and 55 (30.90%) had received previous treatment with other biologics, particu larly infliximab (22.50%). The demographics of the poor adherence group are shown in Table 1.

Table 1. Sociodemographic profile of patients in the low-adherence subgroup 

BMI: body mass index; CD: Crohn's disease; SD: standard deviation; UC: ulcerative colitis.

A mean adherence rate of 91.79% (± 11.62) was obtained for the 178 patients included in the study. Mean adherence was 91.15% for adali mumab, 91.74% for golimumab and 95.05% for ustekinumab (p = 0.045). The pharmacy dispensing records revealed that 45 patients (25.28%) exhi bited low levels of adherence (< 85%).

Within the subgroup of low adherence patients (n = 32), mean ad herence was 75.6% (± 12.95), with no statistically significant differences between the drugs. After administering the MAQ questionnaire to this group of patients, 15 were classified as noncompliant (46.9%) and 17 (53.1%) as compliant. The first question about forgetting to take their medication was answered in the affirmative by 9 patients (28.10%) while the second ques tion on taking the medication at the right time was answered negatively by 20 patients (62.50%). The third and fourth questions were answered in the affirmative by 1 patient (3.10%).

The results of the MPR and the MAQ questionnaire were compared for this subgroup de patients. Mean adherence among patients classified as compliant was 79.33 % (± 10.51); among non-compliant patients it was 71.38% (± 14.46) (p = 0.064).

Lastly, an analysis was made of the relationship between adherence and the demographic and/or clinical factors of both the whole patient popula tion and the low-adherence subgroup. Firstly, an univariate analysis was carried out of the variables studied in both patient groups. Given the high number of variables, concomitant treatments and the type of biologic drug used previously were excluded from the analysis. The results are shown in Table 2 and Table 3.

Table 2. Results of the uni-and multivariate analyses of the total patient sample 

1Chi-squared test or Fisher Exact Test (n < 5). 2Student's t-test for independent samples. 3Multivariate logistic regression. CI: confidence interval; OR: odds ratio.

*p ≤ 0.05.

Table 3. Results of the univariate analysis in the low-adherence subgroup 

1Chi-squared test or Exact Fisher Test (n < 5). 2Student's t-test for independent samples. 3Mann-Whitney Nonparametric U Test for independent samples.

*Subjects with primary and secondary education are grouped separately from those with a university education.BMI: body mass index; CI: confidence interval; FC: fecal calprotectin; OR: odds ratio.

On the multivariate analysis, only female sex and the length of treatment were associated to lower adherence levels (Table 3).

Discussion

The results of the present study show high levels of adherence (91.79%) for the overall patient sample, with 45 patients (25.28%) identified as scar cely compliant.

No reports exist in the literature that compare the adherence to the three subcutaneously administered agents used to treat IBD. The first sys tematic review on the adherence to anti-TNF drugs was published in 2013 and includes 13 studies on 93,998 patients. Four of the studies reviewed determined the patients' adherence to infliximab and adalimumab using the MPR. Mean adherence to adalimumab was shown to be 83.1% (36.8-96%), which is lower than the 91.15% adherence rate found in the present study10. Other, more recent, studies obtained even lower adherence rates for adalimumab (57%) also using the MPR. These diffe rences between earlier studies and the present one could be due to the fact that, in the former, adherence was evaluated over a longer period of time (24 months)19.

A retrospective cohort study from the United States used the MPR rate to study adherence to golimumab and adalimumab in 27 and 226 pa tients respectively. It obtained an adherence rate of 95% for golimumab (similar to our 91.74%) and 77% for adalimumab20. As regards ustekinu mab, no study was found that looked into adherence in an IBP popu lation. Nonetheless, a Canadian study on psoriasis obtained a mean adherence of 93.5%, similar to the 95.05% found in the present study21. However, it must be taken into account that the clinical situations evalua ted are different.

In this study, female sex was found to be associated to poorer therapeu tic adherence, which is in line with earlier findings. In a systematic review, Lopez et al. identified four studies where female sex is associated to poorer adherence10. In the same vein, a Swedish study on golimumab identified women as less compliant (hazard ratio (HR) 6.59; confidence interval (CI): 95%: 1.04-41.62)22. A study on ustekinumab showed higher adherence levels in men (OR =1.28 (1.08-1.51) p= 0.004)23.

In this study it was also found that the longer the treatment, the poorer the adherence. A Spanish study on patients treated with aminosalicylates revealed a statistically significant association (p = 0.05) between increased duration of treatment and poorer adherence24.

Of the total 178 patients, 55 (30.9%) had received some form of pre vious treatment. The most commonly used drug was infliximab (22.5%). In the low adherence subgroup, patients who had received previous treatment had only taken infliximab, which had been discontinued in 72% of them as a result of primary failure in the course of the first few infusions. In line with the findings in this study, an analysis of the persistence to biologic agents in IBD by Chen et al. showed that the majority of patients begin their biologics-based therapy with either adalimumab, which is maintained for a mean of 1.04 years, or infliximab, which is maintained for 0.88 years25. In our study, the 136 patients on adalimumab exhibited a higher persistence rate, with a mean of 2.9 years.

The MAQ questionnaire was administered in our study in order to ob tain a more accurate determination of adherence and to understand who some patients show poor levels of adherence. MAQ was also applied un one of the first studies on patients on mesalamine, but the results obtained were not comparable to those of the present study24. Using a simple set of questions, Billioud et al. concluded that forgetfulness in taking the medi cation was the chief culprit for non-adherence in 24.6% de los patients26.

FC levels were analyzed in order to determine whether lack of adheren ce played a role in the effectiveness of treatment, but the two parameters did not appear to be related in a statistically significant manner. Sipponen et al. found that a 12-week-long treatment with anti-TNF agents resulted in a significant decrease of FC levels (p = 0.001)27.

The present study is subject to several limitations. The main one is re lated to the fact that adherence was monitored over a period of only four months. It has been found that, in the setting of chronic diseases, adherence should be measured over at least six months28. In addition, the percentages presented herein may be slightly distorted as they were calculated on the basis of the date on which the drugs were dispensed, which could have been entered incorrectly. Another shortcoming about this method is that the fact that a drug was dispensed does not necessarily imply that the patient actually administered it29.

Another limitation of this study has to do with its statistical power. The number of patients classified as scarcely compliant was too low for any associations observed in that subgroup of patients to be considered sta tistically significant. It would be useful to include patients on infliximab or vedolizumab in the analysis as this would provide a broader overview of adherence to all biologic agents in the setting of IBD.

Lastly the MAQ questionnaire was selected because it is an easy-to-respond to, general-purpose questionnaire used to measure adherence in patients with chronic conditions. As regards the MMAS-8. although it is a questionnaire specifically validated for IBP, De Castro et al. pointed out that its accuracy in detecting noncompliant patients is questionable30.

On the other hand, one of the strengths of this study lies in the fact that it is the first study to compare the adherence to the three drugs analyzed. It therefore affords a valuable insight into the adherence to the subcutaneous biologic agents used to treat IBD. Moreover, as recommended by other authors, adherence was measured using two indirect methods, namely the MPR rate and the MAQ questionnaire17.

As all the patients included in this study came from one single hospital, the results cannot be extended to the whole European, or even Spanish, po pulation as there may well be demographic, clinical and treatment protocol-related differences between different sites.

To conclude, the adherence rate obtained in the present study is high for the general population and 75% lower for patients classified as scarcely compliant. Female sex and length of treatment were associated to poorer therapeutic adherence.

Bibliography

1. Lennard-Jones JE. Classification of inflammatory bowel disease. Scand J Gastroenterol Suppl. 1989;170:2-6. DOI: 10.3109/00365528909091339 [ Links ]

2. Fernández A, Hernández V, Martínez-Ares D, Sanromán L, Luisa de Castro M, Ramón Pineda J, et al. Incidence and phenotype at diagnosis of inflammatory bowel disease. Results in Spain of the EpiCom study. Gastroenterol Hepatol. 2015;38(9):534-40. DOI: 10.1016/j.gastrohep.2015.03.001 [ Links ]

3. Dutta AK, Chacko A. Influence of environmental factors on the onset and course of inflammatory bowel disease. World J Gastroenterol. 2016;22(3):1088-100. DOI: 10.3748/wjg.v22.i3.1088 [ Links ]

4. Guardiola J, Lobatón T, Cerrillo E, Ferreiro-Iglesias R, Gisbert JP, Domenech E, et al. Recommendations of the Spanish Working Group on Crohn's Disease and Ulcerative Colitis (GETECCU) on the utility of the determination of faecal calprotectin in inflammatory bowel disease. Gastroenterol Hepatol. 2018;41(8):514-29. DOI: 10.1016/j.gastrohep.2018.05.029 [ Links ]

5. Mowat C, Cole A, Windsor A, Ahmad T, Arnott I, Driscoll R, et al. Guidelines for the management of inflammatory bowel disease in adults. Gut. 2011;60(5):571-607. DOI: 10.1136/gut.2010.224154 [ Links ]

6. Cabriada JL, Vera I, Domenech E, Barreiro-de Acosta M, Esteve M, Gisbert JP, et al. Recommendations of the Spanish Working Group on Crohn's Disease and Ulcerative Colitis on the use of anti-tumor necrosis factor drugs in inflammatory bowel disease. Gastroenterol Hepatol. 2013;36(3):127-46. DOI: 10.1016/j.gastrohep.2013.01.002 [ Links ]

7. Peyrin-Biroulet L, Loftus EV Jr, Colombel JF, Sandborn WJ. Early Crohn disease: a proposed definition for use in disease-modification trials. Gut. 2010;59(2):141-7. DOI: 10.1136/gut.2009.187120 [ Links ]

8. Dignass A, Lindsay JO, Sturm A, Windsor A, Colombel JF, Allez M, et al. Second European evidence-based consensus on the diagnosis and management of ulcerative colitis Part 2: Current management. J Crohns Colitis. 2012;6(10):991-1030. DOI: 10.1016/j.crohns.2012.09.002 [ Links ]

9. Burkhart PV, Sabate E. Adherence to long-term therapies: Evidence for action. J Nurs Scholarsh. 2003;35(3):207. DOI: 10.1016/S1474-5151(03)00091-4 [ Links ]

10. López A, Billioud V, Peyrin-Biroulet C, Peyrin-Biroulet L. Adherence to Anti-TNF Therapy in Inflammatory Bowel Diseases: A Systematic Review. Inflamm Bowel Dis. 2013;19(7):1528-33. DOI: 10.1097/MIB.0b013e31828132cb [ Links ]

11. Carter CT, Waters HC, Smith DB. Effect of a continuous measure of adherence with infliximab maintenance treatment on inpatient outcomes in Crohn's disease. Patient Prefer Adherence. 2012;6:417-26. DOI: 10.2147/PPA.S31115 [ Links ]

12. Vangeli E, Bakhshi S, Baker A, Fisher A, Bucknor D, Mrowietz U, et al. A Systematic Review of Factors Associated with Non-Adherence to Treatment for Immune-Mediated Inflammatory Diseases. Adv Ther. 2015;32(11):983-1028. DOI: 10.1007/s12325-015-0256-7 [ Links ]

13. Morisky DE, Green LW, Levine DM. Concurrent and predictive validity of a self-reported measure of medication adherence. Med Care. 1986;24:67-74. DOI: 10.1097/00005650-198601000-00007 [ Links ]

14. Severs M, Zuithoff PN, Mangen MJ, van der Valk ME, Siersema PD, Fidder HH, et al. Assessing Self-reported Medication Adherence in Inflammatory Bowel Disease: A Comparison of Tools. Inflamm Bowel Dis. 2016;22:2158-64. DOI: 10.1097/MIB.0000000000000853 [ Links ]

15. Selinger CP, Eaden J, Jones DB, Katelaris P, Chapman G, McDonald C, et al. Modifiable factors associated with nonadherence to maintenance medication for inflammatory bowel disease. Inflamm Bowel Dis. 2013;19:2199-206. DOI: 10.1097/MIB.0b013e31829ed8a6 [ Links ]

16. Trindade AJ, Ehrlich A, Kornbluth A, Ullman TA. Are your patients taking their medicine? Validation of a new adherence scale in patients with inflammatory bowel disease and comparison with physician perception of adherence. Inflamm Bowel Dis. 2011;17:599-604. DOI: 10.1002/ibd.21310 [ Links ]

17. Van der Have M, Oldenburg B, Kaptein AA, Jansen JM, Scheffer RCH, van Tuyl BA, et al. Non-adherence to Anti- TNF Therapy is Associated with Illness Perceptions and Clinical Outcomes in Outpatients with Inflammatory Bowel Disease: Results from a Prospective Multicentre Study. J Crohns Colitis. 2016;10(5):549-55. DOI: 10.1093/ecco- jcc/jjw002 [ Links ]

18. Ibarra Barrueta O, Morillo Verdugo R. Lo que debes saber sobre la adherencia al tratamiento. Barcelona: Euromedice; 2017. [ Links ]

19. Wentworth BJ, Buerlein RCD, Tuskey AG, Overby MA, Smolkin ME, Behm BW. Nonadherence to Biologic Therapies in Inflammatory Bowel Disease. Inflamm Bowel Dis. 2018;24(9):2053-61. DOI: 10.1093/ibd/izy102 [ Links ]

20. Khilfeh I, Guyette E, Watkins J, Danielson D, Gross D, Yeung K. Adherence, Persistence, and Expenditures for High-Cost Anti-Inflammatory Drugs in Rheumatoid Arthritis: An Exploratory Study. J Manag Care Spec Pharm. 2019;25(4):461-7. DOI: 10.18553/jmcp.2019.25.4.461 [ Links ]

21. Hsu DY, Gniadecki R. Patient Adherence to Biologic Agents in Psoriasis. Dermatology. 2016;232(3):326-33. DOI: 10.1159/000444581 [ Links ]

22. Rundquist S, Eriksson C, Nilsson L, Angelison L, Jaghult S, Bjork J, et al. Clinical effectiveness of golimumab in Crohn's disease: an observational study based on the Swedish National Quality Registry for Inflammatory Bowel Disease (SWIBREG). Scand J Gastroenterol. 2018;53(10-11):1257-63. DOI: 10.1080/00365521.2018.1519597 [ Links ]

23. Doshi JA, Takeshita J, Pinto L, Li P, Yu X, Rao P, et al. Biologic therapy adherence, discontinuation, switching, and restarting among patients with psoriasis in the US Medicare population. J Am Acad Dermatol. 2016;74(6):1057-65. DOI: 10.1016/j.jaad.2016.01.048 [ Links ]

24. Lopez A, Billioud V, Peyrin-Biroulet C, Peyrin-Biroulet L. Adherence to Anti-TNF Therapy in Inflammatory Bowel Diseases: A Systematic Review. Inflamm Bowel Dis. 2013;19(7):1528-33. DOI: 10.1097/MIB.0b013e31828132cb [ Links ]

25. Chen C, Hartzema AG, Xiao H, Wei YJ, Chaudhry N, Ewelukwa O, et al. Real-world Pattern of Biologic Use in Patients With Inflammatory Bowel Disease: Treatment Persistence, Switching, and Importance of Concurrent Immunosuppressive Therapy. Inflamm Bowel Dis. 2019;25(8):1417-27. DOI: 10.1093/ibd/izz001 [ Links ]

26. Billioud V, Laharie D, Filippi J, Roblin X, Oussalah A, Chevaux JB, et al. Adherence to Adalimumab Therapy in Crohn's Disease: A French Multicenter Experience. Inflamm Bowel Dis. 2011;17(1):152-9. DOI: 10.1002/ibd.21491 [ Links ]

27. Sipponen T, Savilahti E, Karkkainen P, Kolho KL, Nuutinen H, Turunen U, et al. Fecal Calprotectin, Lactoferrin, and Endoscopic Disease Activity in Monitoring Anti-TNF-alpha Therapy for Crohn's Disease. Inflamm Bowel Dis. 2008;14(10):1392-8. DOI: 10.1002/ibd.20490 [ Links ]

28. McMahon J, Jordon M, Kelley K, Bertagnolio S, Hong S, Wanke C, et al. Pharmacy adherence measures to assess adherence to antiretroviral therapy: Review of the literature and implications for treatment monitoring. Clin Infect Dis. 2011;52(4):493-506. DOI: 10.1093/cid/ciq167 [ Links ]

29. Pages-Puigdemont N, Isabel Valverde-Merino M. Methods to assess medication adherence. Ars Pharm. 2018;59(3):163-72. DOI: 10.30827/ars.v59i3.7387 [ Links ]

30. De Castro ML, Sanromán L, Martín A, Figueira M, Martínez N, Hernández V, et al. Valoración de la adhesión terapéutica en la enfermedad inflamatoria intestinal. Comparación entre una escala de autoevaluación y un índice farmacéutico de dispensación de medicamentos. Rev Esp Enferm Dig. 2017;109(8):542-51. DOI: 10.17235/reed.2017.5137/2017 [ Links ]

Funding: No funding.

Contribution to the scientific literature:

Low adherence to treatment reduces therapeutic effectiveness and negatively impacts patients' quality of life, resulting in increa sed hospital admissions and higher healthcare costs. Several studies have been published on adherence in the setting of immunological disorders, but most of them focus on one or more of the first mo noclonal antibodies that reached the market, such as infliximab o adalimumab. As far as inflammatory bowel disease is concerned, no original study has yet been published that looks into the adhe rence to the three subcutaneously administered monoclonal antibo dies approved for this indication, i.e. adalimumab, golimumab and ustekinumab.

An understanding of adherence to medication in the inflammatory bowel disease population is crucial to detect patients with poor thera peutic adherence. Once these patients have been identified, healthca re providers can develop interventions geared toward boosting adhe rence and achieving therapeutic success.

How to cite this paper: Calvo-Arbeloa M, Insausti-Serrano AM, Arrondo-Velasco A, Sarobe-Carricas MT. Adherence to treatment with adalimumab, golimumaband ustekinumab in patients with inflammatory bowel disease. Farm Hosp. 2020;44(2):62-7.

Received: September 13, 2019; Accepted: December 16, 2019

Author of correspondence María Calvo Arbeloa Servicio de Farmacia Complejo Hospitalario de Navarra Calle Irunlarrea, 3, 31008 Pamplona (Navarra), Spain. Email: mariacn640@gmail.com.

Conflict of interests

No conflict of interest.

Creative Commons License This is an open-access article distributed under the terms of the Creative Commons Attribution License