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Implementation of the French national consensus for the management of ulcerative colitis into clinical practice

Digestive and Liver Disease, In Press, Corrected Proof, Available online 3 September 2016, Available online 3 September 2016

Abstract

Background

Recently, treatment algorithms were developed in France additionally to ECCO recommendations that should be used as reference for ulcerative colitis (UC) management. Nevertheless, their implementation in clinical practice remains challenging.

Aims

To evaluate the prevalence of the use of these UC management algorithms in 127 patients followed by private gastroenterologists.

Methods

Charts of all UC patients seen during the year 2015 (n = 127) by 10 gastroenterologists were reviewed. The gastroenterologist’s management was then compared to the corresponding algorithm situation and, in case of disagreement, analysed by an expert committee.

Results

94.5% of patients corresponded to a clinical situation described in algorithms. Gastroenterologist’s management was adequate to the corresponding algorithm situation in 74.2% of cases. Among the 31 cases of disagreement, the gastroenterologist’s decision differed from the algorithm position in 21 cases, and in 76.2% of cases the expert committee would have made the same decision. In the remaining 10 cases, the decision differed from the corresponding algorithm for reasons independent from the gastroenterologist (patient’s choice etc.).

Conclusions

French national algorithms for UC management allowed coverage of 95% of clinical cases in real world. In three quarters of cases, these algorithms were strictly followed by private gastroenterologists. Dissemination of these algorithms could optimize and strengthen the practitioner’s choice.

Keywords: Decision support, Inflammatory bowel disease, Treatment algorithms.

1. Introduction

Ulcerative colitis (UC) is the most common inflammatory bowel disease (IBD) [1] and [2], characterised by an alternation of phases of activity of varying intensity and symptom-free phases. Its management is complex because the characteristics of the disease vary in display, evolution, and response to drugs [1] and [3].

In 2012, the European Crohn’s and Colitis Organisation (ECCO) issued recommendations [4] and [5] complementary to those of 2008 that accurately validate the use of oral or topical salicylates (5-aminosalicylic acid [5-ASA] or mesalamine), as well as oral or topical corticosteroids. The ECCO 2012 recommendations focus on management of the attacks and maintenance treatment on ASA, and include the most actual clinical practices in ulcerative colitis (UC). The therapeutic roles of immunosuppressants (azathioprine, methotrexate, and cyclosporine) and anti-tumor necrosis factor alpha (TNFα) (infliximab, adalimumab, or golimumab) are less consensual however, mainly because indications for these newer compounds are currently being investigated. Thus, in 2015, a French national consensus of clinical guidelines for the management of UC led to publish algorithms called “algorithMICI” [6] and [7] that take international recommendations, current practice, and new therapies into consideration. In this consensus, first line management of mild to moderate UC and proctitis was not reviewed, and the ECCO 2012 recommendations were followed. On the other hand, treatment of moderate to severe UC (excluding proctitis), acute severe UC requiring hospitalisation, refractory proctitis, and pouchitis were actively discussed.

The aim of this study was to evaluate the prevalence of the management algorithms in a private cohort of UC practitioners in 2015, and the actual quality of medical care provided by the gastroenterologists of the study as compared to standards.

2. Methods

In order to evaluate the use of UC management algorithms by private physicians, 10 gastroenterologists specialised in IBD management were identified. All participating physicians have over 5 years of experience in the management of IBD (range, 5–35 years) and they follow a mean of 24.4 IBD patients/year (range, 6–102). They all work in private hospitals with an emergency unit and an inpatient care unit. None of them work in a Teaching Hospital or in an IBD unit. Their competences were evaluated based on their participation in at least two IBD-related courses (continuing medical education, CME) annually for the past 3 years.

127 patients diagnosed with UC seen in 2015 were included in the cohort. The French healthcare system offers patients relatively easy access to specialist care (in this case, gastroenterologists). The vast majority of patients were referred by general practitioners.

As a chronic disease, UC treatment is 100% reimbursed in the French healthcare system in accordance with the conditions applied in France.

Data from consultations were standardised and entered in real time using EasyMICI software (IBD electronic Health Record) over the course of year 2015. Following the decision of the data review, the database was locked.

The definitions of clinical situations are described in Appendix A, they follow the ECCO 2012 recommendations and the International Organisation for the Study of Inflammatory Bowel Diseases/Selection of the Therapeutic Target in Inflammatory Bowel Disease (IOIBD/STRIDE) 2015 [4], [5], and [8].

From those definitions, each patient was matched with a clinical situation described either by simple algorithms based on ECCO recommendations 5A, 5B, 5C, 6B, 6D and 6E, or by the “algorithMICI” [6] and [7] published in 2016.

Recently we published the French national consensus on the management of UC [6] and [7], based on literature data and adapted to patient management practices in France. Five clinical situations were discussed during this consensus and led to the development of algorithms: relapse of moderate UC on 5-ASA maintenance treatment, severe UC, severe acute UC requiring hospitalization, refractory proctitis and pouchitis. For mild to moderate UC, ECCO recommendations 5A, 5B, 5C, 6B, 6D and 6E on 5-ASA and corticosteroids as induction and maintenance treatment were used as reference, as these clinical situations were not addressed by the French national consensus.

Patient data were classified into six groups:

  • - Group 0: patient situation did not match any algorithms;
  • - Group 1: patient situation matched with the initial and maintenance treatment of UC with 5-ASA and corticosteroids algorithm (“ECCO algorithm”);
  • - Group 2: patient situation matched with moderate to severe UC algorithm (algorithMICI);
  • - Group 3: patient situation matched with severe acute UC requiring hospitalisation algorithm (algorithMICI);
  • - Group 4: patient situation matched with refractory proctitis algorithm (algorithMICI);
  • - Group 5: patient situation matched with pouchitis algorithm (algorithMICI)

When a patient situation matched an algorithm – “ECCO algorithm” [5] (Group 1) or one of the “algorithMICI” [6] and [7] (Group 2, 3, 4 or 5) – the management of UC elected by the gastroenterologist was compared to the recommended treatment described in the corresponding algorithm.

In case of discrepancy between the gastroenterologist's practice and the algorithm relevant to the situation, the choice supported by the investigator was classified into three categories:

  • 1) Therapeutic choice is different from algorithm (discordant),
  • 2) Therapeutic choice is in theoretical agreement with the algorithm but refused by the patient,
  • 3) Therapeutic choice is in theoretical agreement with the algorithm but unsuccessful in practice for administrative and/or financial reasons.

Therapeutic choices different from the algorithm, called “discordant”, were analysed by an experts’ committee comprised of three practitioners. The committee labelled discordances as “debatable therapeutic choice”, and either decided to maintain the elected treatment option (with possible request for further information), or proposed a change in therapy if the position was not acceptable.

The independent sample test (Student’s test) was used to compare the results.

3. Results

3.1. Distribution of patients into clinical situation groups

The distribution of 127 UC patients among the situations described in the algorithms is shown in Table 1. Of the 127 patients, 120 (94.5%) matched one of the algorithms, and for the majority, matched the algorithms based on ECCO recommendations (68/120; 56.7%).

Table 1

Distribution of 127 patients according to the algorithms.

 

Group N %
Group 0 7 5.5
Group 1 68 53.5
Group 2 44 34.6
Group 3 3 2.4
Group 4 4 3.2
Group 5 1 0.8
Groups 1–5 120 94.5

Group 0: patient situation did not match any algorithms. Group 1: patient situation matched with “ECCO algorithm”-ECCO statement 5A, 5B, 5C, 6B, 6E [5]. Group 2: patient situation matched with moderate to severe UC algorithm [6] and [7]. Group 3: patient situation matched with severe acute UC requiring hospitalisation algorithm [6] and [7]. Group 4: patient situation matched with refractory proctitis algorithm [6] and [7]. Group 5: patient situation matched with pouchitis algorithm [6] and [7]. Note: ECCO: European Crohn’s and Colitis Organisation, UC: ulcerative colitis.

Seven cases (5.5%) did not match any clinical situation described in one of the algorithms (Table 2). Two of these cases corresponded to an interruption of the maintenance treatment with azathioprine, initiated by the patient or the physician, without any indication of relapse management. Two other cases were either relapse or side effect occurring while on maintenance therapy with azathioprine, which was initially effective. One case involved treatment failure improved by pregnancy. One case described side effects during maintenance treatment with anti-TNFα, in a patient who had presented a prolonged remission. Finally, one case involved a situation of early side effect related to azathioprine.

Table 2

Description of patients non-concerned by a clinical situation described in algorithms.

 

Patient 1 Quiescent UCa E2 treated with azathioprine. Discontinuation of the treatment by the patient. Relapse at 6 months. Clinical situation management not described in the algorithm. Treatment with azathioprine and corticosteroids
 
Patient 2 Quiescent UCa E3 treated with azathioprine. Discontinuation of the treatment by the patient. Relapse at 9 months with moderate UCa activity (Mayo 6). Clinical situation management not described in the algorithm. Treatment with azathioprine and oral 5-ASAb (Remission obtained)
 
Patient 3 UCa E3 initially severe non-hospitalised, steroid-dependent patient weaned when treated with azathioprine. New flair after 1 year. Indication of relapse management undefined in the algorithm
 
Patient 4 Quiescent refractory proctitis treated with azathioprine. Occurrence of Nodular regenerative hyperplasia after 5 years. Clinical situation management not described in the algorithm
 
Patient 5 Moderate UCa E3, steroid- refractory with treatment failure of optimised anti-TNFαc treatment (w12). Gastroenterologist projected treatment with vedolizumab but patient improvement was noted without treatment during a period of wash-out satellite pregnancy. Patient’s management after pregnancy undefined in the algorithm
 
Patient 6 Moderate UCa E3, corticosteroid-dependent, treatment with azathioprine failed. Remission obtained with adalimumab treatment. Maintenance treatment with anti-TNFαc allowed quiescent state for 2 years but treatment was stopped for side effects. Clinical situation management not described in the algorithm
 
Patient 7 88 years old patient. Moderate UCa E2 steroid-dependent. Hepatitis immunoallergic to azathioprine. Clinical situation management not described in the algorithm

a UC: ulcerative colitis.

b 5-ASA: 5-aminosalicylic acid.

c TNFα: tumor necrosis factor alpha.

The distribution of cases represented by the algorithms (Groups 1–5) is shown in Table 3 according to UC phenotype, using the Montreal classification [4].

Table 3

Distribution by ulcerative colitis phenotype.

 

Groups Ulcerative colitis type (Montreal classification)
E1 E2 E3 Total
Included in the algorithms 1 40 (90%) 18 (45%) 10 (27.8%) 68
2 0 22 (55%) 22 (61.1%) 44
3 0 0 3 (8.3%) 3
4 4 (10%) 0 0 4
5 0 0 1 (2.8%) 1
Total (100%) 44 (100%) 40 (100%) 36 (100%) 120 (100%)

3.2. Comparison between practice behaviors and recommendations in the algorithms

Among the 120 patient situations matching an algorithm scenario, disease management by the attending gastroenterologist was the same as that of the algorithm in 89 cases (74.2%): 61/68 (89.7%) in group 1 versus 28/52 (53.8%) in groups 2–5 (p < 0.05).

Analysis of discrepancies

Among the 31 cases of discrepancies, a discordant therapeutic choice by the physician was involved in 21 cases (67.8%), the investigator’s therapeutic choice theoretically in agreement with the algorithm was refused by the patient in 5 cases (16.1%), the investigator’s therapeutic choice theoretically in agreement with the algorithm was unsuccessful in practice for administrative and/or financial reasons in 5 cases (16.1%).

An expert panel composed of three physicians analysed the 21 discordant cases, classifying them as “debatable therapeutic choice” or “acceptably discordant” and maintained the treatment option with possible request for additional information in 16/21 cases (76.2%), or as “unacceptably discordant” and suggested a therapeutic change in 5/21 cases (23.8%).

Among the 5 cases “unacceptably discordant”, 2 were about under treatment with maintenance of excessive oral or topical corticosteroid therapies (1 case each). One other case involved overtreatment with unjustified initiation of immunosuppressant after a moderate steroid-sensitive flare. And the last 2 cases involved the right choice of first line treatment with 5-ASA but inadequate dose or route of administration (1 case each).

Of the 16 cases “acceptably discordant”, most (11 cases) continued on 5-ASA therapy associated with immunosuppressant and/or biological therapy as maintenance treatment. Four cases were related to pancolitis with a partial response to immunosuppressive and/or anti-TNFα, with residual low proctitis controlled by local topical treatments rather than change of maintenance therapy. Finally, in 1 case, maintenance of combined therapy after secondary lack of response to a first line monotherapy with TNFα antagonists, despite a satisfactory residual rate received a posteriori.

4. Discussion

In this study, the use of complete and updated algorithms available in 2015 for the management of UC allowed a coverage of 95% of clinical situations. Consequently, these algorithms represent a solid tool to support decision-making, applicable to most real life clinical situations. This patient cohort also seemed representative of the general UC population, as evidenced by the proportion of refractory proctitis (about 10% of proctitis) [4].

This work motivates the need to update and clarify UC management algorithms regularly. Indeed, half of the UC clinical situations are represented in the recently published algorithms “AlgorithMICI” [6] and [7], in addition to simpler algorithms based on the ECCO 2012 recommendations (5A, 5B, 5C, 6B, 6D and 6E) on 5-ASA and corticosteroids as induction and maintenance treatment for mild to moderate UC [5].

The utility of algorithms in medicine has been clearly demonstrated for many years, reducing the risk of errors in medical care and improving treatment relevance and cost control [8] and [9]. The Algorithm is a help decision-maker that could improve quality of care, and in particular help standardise the management of this chronic disease across the country. The problem is often insufficient compliance with recommendations in practice [9] and [10]. In our study, we found that these algorithms were strictly applied in 75% of cases. This proportion seems high compared to results of usual recommendation monitoring surveys, but gastroenterologists investigators selected in this study attended continuous certified training (CME) on the management of IBD, particularly in the last 2 years. Compliance with algorithms is particularly satisfying when the clinical situation matched an “ECCO algorithm” (90% agreement), while only 50% of concordance was observed in the groups matching “algorithMICI”. This observation confirms a lesser penetration and observance of good practice when immunosuppressant and/or biotherapy are used. Our findings revive the debate about the necessity not only to regularly update instructions on good practice, but more importantly to quickly disseminate the information and tools to practitioners. The publication of these additional algorithms should be a useful tool to facilitate therapeutic management of UC in 2016.

A system designed to support clinical decision-making should include validation of patient case positioning using a regularly updated algorithm. Thus, referral to the expert committee would only happen in cases of discrepancy between the algorithmic position and the practitioner’s (i.e., about 20% of cases), and in cases not covered by an algorithm. This hybrid and complementary approach would be preferable to the current French administrative trend. Mandatory therapy validation by an expert committee in the case of hepatitis C [11] and [12] is an example of burdensome, expensive, and unjustified procedures. The involvement of an expert committee for discordant cases could also eventually enrich the algorithmic tool, since we observed that 75% of the discrepancies were in fact acceptable, and missing in the existing algorithmic tools.

There are some limitations to these algorithms that should be taken into account. First, the study presented here was a preliminary study, conducted in a cohort of 127 patients followed by 10 private gastroenterologists, possibly not sufficiently representative of the French gastroenterologists’ population. Secondly, the algorithms are not intended to substitute for training or clinical experience of the practitioner. The figurative use of these algorithms – whether in paper or digital form – requires the practitioner to have IBD experience and prior knowledge of the definitions of the points of entry into the decisional pathway (i.e., criteria for definition of patient clinical situation, such as disease severity, aggravating factors etc.), and their subsequent observance. Moreover, our study points out that a slight variation in UC management will not be matched to an algorithm, even when the patient’s situation actually matched the algorithm. Consequently, strict non-compliance with the algorithms is rarely the result of the practitioner’s lack of knowledge when continuing medical education was previously validated, since the elected therapeutic position is usually maintained by the committee of experts. The practitioner’s IBD experience is therefore crucial not only to ensure correct use of the algorithms, but also when variations in UC management with regard to the algorithms call for decision-making by the practitioner.

The non-compliance to follow recommended algorithms potentially harmful to the patient, concerned only 12.5% ​​(15/120) of patients: 5 cases of either medication error by the practitioner, or patient's refusal to follow a scientific recommendation, or delay in the treatment reimbursement by institutions. Even though these cases are relatively rare, referral to an expert committee for therapeutic advice could help eliminate medication errors by a practitioner.

Further development of this tool could allow structured data entry in a software that would be by itself able to validate the definition and even the positioning of the patient's situation in the algorithm. Further validation of these algorithmic tools in clinical practice is nevertheless required before addressing the underlying technical challenges.

Conflicts of interest

Guillaume BONNAUD (AbbVie, Aptalis, Covidien, Ferring, HAC-pharma, Hospira, MSD, Norgine, Takeda), Audrey HEANNIG (none), Jonathan LEVY (none), Nicolas SIGUR (none), Alain LEDIT (none), Philippe CABARROT (none), Patrick FAURE (MSD, AbbVie, Takeda, Norgine), Catherine AUZIMOUR (Shire, Takeda), Asmaa EL ATMANI (Shire, Takeda), Xavier HEBUTERNE (AbbVie, ARARD, Baxter, Fresenius-Kabi, MSD, Nestlé, Nutricia, Takeda, Vifor), Laurent PEYRIN-BIROULET (AbbVie, BMS, Boerhinger-Ingelheim, Celltrion, Ferring, Genentech, HAC-pharma, Hospira, Janssen, Lilly, Merck, Mitsubishi, Norgine, Pharmacosmos, Pilège, Shire, Takeda, Therakos, Tillots, UCB-pharma, Vifor).

Funding

This work has benefited from institutional support from Takeda.

Appendix A. Definitions

Ulcerative colitis (UC) is a chronic inflammatory condition causing ongoing mucosal inflammation of the colon without granulomas on biopsy, affecting the rectum and, to a varying extent, the colon in its continuity, characterised by alternating recurrences and remission [4].

The refractory proctitis is defined as the absence of remission or improvement after 2 months of treatment with 5-ASA local, with or without treatment with oral salicylates and a month of treatment with local steroid.

Pouchitis is an inflammation of the ileal pouch that appear after total colectomy with ileal pouch-anal anastomosis. The diagnosis of pouchitis is based on clinical symptoms, endoscopic and histological. The score Pouchitis Disease Activity Index (PDAI) is used to diagnose pouchitis. An active pouchitis is defined by an upper PDAI score ≥7.

Mayo score: ulcerative colitis activity index (excluding proctitis) [4]

Criteria Points
Stool frequency per day Normal: 0
1–2 stool: 1
3–4 stool: 2
>5 stool: 3
 
Rectal bleeding No blood: 0
Traces of blood less than 50%: 1
Mostly obvious hematuria: 2
Bleeding outside stool: 3
 
Endoscopic observation Normal observation or inactive disease: 0
Mild colitis (erythema, slightly dry mucosa): 1
Moderate colitis (visible erythema, erosion, no vascular pattern): 2
Severe colitis (ulcers, spontaneous bleeding): 3
 
Physician’s global assessment Normal: 0
Mild disease: 1
Moderate disease: 2
Severe disease: 3

Moderate active UC: active UC defined by a Mayo activity score less than or equal to grade 9.

Severe active UC: active UC defined by a Mayo activity score higher than grade 9.

Remission is defined as the complete resolution of symptoms and endoscopic mucosal healing. In clinical practice, the ECCO considers that there is remission when the stool frequency is less than or equal to 3 bowel movements a day without bleeding or any emergency [4].

Response is defined as clinical and endoscopic improvement, as the activity score used (in clinical trials). In general, response corresponds to >30% decrease in the rectal bleeding and endoscopic subscores [4].

Relapse is defined as a flare of symptoms in a patient with established UC who is in clinical remission, either spontaneously or after medical treatment. According to the ECCO consensus, relapse is characterised by rectal bleeding, which may be associated or not with an increase in stool frequency and mucosal abnormalities at sigmoidoscopy [4].

Steroid-refractory colitis is an active disease despite taking up to 0.75 mg/kg/day of prednisolone over a 4-week period [4].

Steroid-dependent colitis: inability to reduce the steroid dose below 10 mg/day of prednisolone (or equivalent) within 3 months after initiation of corticosteroid therapy without recurrence of active disease, or relapse within 3 months stopping corticosteroids [4].

Colitis refractory to immunosuppressants: according to the ECCO, active disease or relapse despite treatment with thiopurine by a suitable dose for at least 3 months (e.g. azathioprine 2–2,5 mg/kg/day or mercaptopurine 0,75–1 mg/kg/day in the absence of leukopenia) [4].

No response to anti-TNFα therapy: the response can be primary or secondary (non-response occur after an initial response to treatment followed by a relapse).

Stable (if anti-TNFα): sustainable response to treatment.

Therapeutic escape (if anti-TNFα): loss of response can occur after an initial treatment response (secondary non-response).

Pharmacokinetics assay: assay used to evaluate the residual anti-TNFα levels and the level of antibodies directed against TNFα antagonist.

Inaugural flare (mild and moderate UC): management according the “statement 5A (proctitis), 5B (left colitis) and 5C (colitis),” the recommendations of ECCO 2012 [5].

Weaning (corticosteroids): response to steroid therapy and absence of relapse or recurrence after reducing the dose or stopping treatment.

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Footnotes

a Clinique Ambroise Paré, Toulouse, France

b Clinique des cèdres, Cornebarrieu, France

c Clinique Pasteur, Toulouse, France

d KPL, Paris, France

e Service d’hépato-gastroentérologie, CHU, Nice, France

f Service d’hépato-gastroentérologie, CHU, Nancy, France

Corresponding author.