Appropriateness of therapy for fistulizing Crohn’s disease: findings from a national inflammatory bowel disease cohort
Article first published online: 18 AUG 2010
© 2010 Blackwell Publishing Ltd
Alimentary Pharmacology & Therapeutics
Volume 32, Issue 8, pages 1007–1016, October 2010
How to Cite
Pittet, V., Juillerat, P., Michetti, P., Vader, J.-P., Burnand, B., Rogler, G., Beglinger, C., Seibold, F., Mottet, C., Felley, C., Gonvers, J.-J., Froehlich, F. and The Swiss IBD Cohort Study Group (2010), Appropriateness of therapy for fistulizing Crohn’s disease: findings from a national inflammatory bowel disease cohort. Alimentary Pharmacology & Therapeutics, 32: 1007–1016. doi: 10.1111/j.1365-2036.2010.04434.x
- Issue published online: 26 SEP 2010
- Article first published online: 18 AUG 2010
- Publication data Submitted 17 March 2010 First decision 20 April 2010 Resubmitted 24 June 2010 Accepted 25 July 2010
Aliment Pharmacol Ther 2010; 32: 1007–1016
Background About 30–50% of patients with Crohn’s disease (CD) develop fistulae, implying significant disease burden and complicated clinical management.
Aim To assess appropriate use of therapy for fistulizing CD patients enrolled in the Swiss Inflammatory Bowel Disease Cohort using criteria developed by the European Panel on the Appropriateness of Crohn’s disease Therapy.
Methods Specific questionnaires were used to gather information on disease and its management. We assessed appropriateness of therapy at enrolment for adult CD patients with one or several fistulae.
Results Two hundred and eighty-eight CD patients had fistulizing disease, of which 80% had complex fistulae and 32% currently had active draining fistulae. Mean age (s.d.) at diagnosis was 27 years (11), 51% males. Of the patients, 78% were judged as having globally an appropriate therapy, which was more often given for complex fistulae (87%) than for simple fistulae (67%). Antibiotics, azathioprine/MP, methotrexate and conservative surgery were almost always appropriate. Anti-tumor necrosis factor α was considered globally appropriate (91%), although most often with an uncertain indication. The 5ASA compounds, steroids and aggressive surgery were most often inappropriate (84%, 58% and 86% respectively).
Conclusions Formal appropriateness criteria for CD therapy were applied to a national cohort of IBD patients. For more than three-quarters of the patients with fistulizing CD, therapy was globally appropriate.
Crohn’s disease (CD) has a natural history of relapsing acute phases followed by remission. The development of fistulae in the course of the disease is a common complication and is considered a consequence of transmural inflammation. The cumulative incidence of fistulae in CD varies from 33%, 10 years after diagnosis, to 50%, 20 years after diagnosis.1, 2
The treatment of fistulae depends on the location, severity of symptoms and complexity of the fistula tracts. Asymptomatic fistulae often require no intervention, but more complex fistulae associated with abscesses may require surgery.3 Management of therapy for fistulizing CD is complex because of associated morbidity.4, 5 Adequate diagnosis and appropriate therapy for patients with fistulae are important elements of quality of care for these patients. Deriving evaluation on appropriateness of care from available studies is difficult because clinical trials are often uncontrolled, and treatment decisions guided mainly by clinical experience rather than by randomized clinical trial results.
It is thus important to assess appropriateness of treatment of patients with fistulizing CD, using explicit, objective criteria. A treatment is considered appropriate if the expected benefits to the patient sufficiently exceed the risks that the treatment is worth giving. To assess appropriateness of care for CD patients, the European Panel on the Appropriateness of Crohn’s disease Therapy (EPACT II) convened in 2007 with a panel of 12 experts to update criteria previously established in 2004. A validated and standardized method (RAND/UCLA)6, 7 elicited expert opinion to formulate recommendations on specific clinical situations encountered by clinicians in their daily practice. Panel members used a specifically structured updated literature review, combined with their own best clinical expert judgment, to assess the appropriateness of a specific treatment. Common scenarios that took into account the majority of relevant situations in clinical practice were identified.
We applied the updated EPACT II appropriateness criteria to Crohn’s disease patients enrolled in the Swiss Inflammatory Bowel Disease Cohort Study (SIBDCS); data were collected at enrolment by means of specifically designed questionnaires containing all the information needed on the course of the disease as well as current patient status, to produce a decision on the appropriateness of treatment, using the EPACT II criteria.
The aim of this study was to assess the appropriateness of treatment of fistulizing CD patients, at baseline, using the EPACT II criteria and data from the SIBDCS.
The SIBDCS started in November 2006.8 One of the major aims was to document medical care to assess the appropriateness of care of CD patients. For this purpose, data were collected at the time of enrolment as well as during annual follow-ups, by means of specifically designed questionnaires containing the requisite variables for EPACT II criteria evaluation. Questionnaires were filled in by the gastroenterologist enrolling the patient in the cohort or by a trained study nurse. The questionnaire documented current status (severity of the disease, disease location, laboratory values, therapy and supplementations, alternative medicine, medical assessment of the clinical situation and associated management decisions) and past medical history (initial disease location, smoking status, use of non-steroidal anti-inflammatory drugs (NSAIDs), family history of IBD, fistulae, stenosis and other complications, extraintestinal manifestations, operations, past therapy). Completed questionnaires were sent to the cohort data centre for data entry and validation.
Patients were recruited in six major tertiary care centres, as well as in regional hospitals and private practices. At the initial visit, eligibility for inclusion was checked by means of a screening form. Inclusion criteria were a diagnosis of CD established at least 4 months prior to inclusion or after at least one recurrence of the signs and symptoms. Case ascertainment was based on the Lennard-Jones criteria9 and confirmed by radiological, endoscopic or histological findings. Written informed consent was obtained from each participating patient. The selection of patients with a fistulizing disease phenotype10 corresponded to those presenting at least an individual clinical situation characterized by a currently ongoing simple or complex fistula11 or having had at least one fistula once in the course of their disease.
The EPACT II appropriateness criteria were established for nine broad clinical situations in CD (Table 1): active luminal CD, steroid-dependent or -refractory disease, fistulizing CD, fibro-stenotic CD, upper gastrointestinal CD or extraintestinal manifestations of CD, maintenance of a medically induced or surgically induced remission of CD.12 Definitions were developed to classify typical patients to be included in each of these clinical situations. The cohort study questionnaires were developed to facilitate inclusion of cases in corresponding clinical situations, by collecting data on variables linked to EPACT II definitions. Certain clinically reasonable definitions were used to apply the criteria to SIBDCS patients (Table 1).
|Major clinical categories||Definitions|
|Mild-to-low moderate active luminal CD||150 < CDAI < 300 No current stenosis No current fistula No current abscess|
|High moderate to severe active luminal CD||CDAI ≥ 300 No current stenosis No current fistula No current abscess|
|Steroid-dependent CD||CDAI ≤ 220 Past steroid therapy that was stopped because of a breakthrough or because no longer needed Current steroid therapy With a flare at enrolment or under treatment|
|Steroid-refractory CD||CDAI > 220 Past steroid therapy that was stopped because of a breakthrough or because no longer needed Current steroid therapy With a flare at enrolment or under treatment|
|Fistulizing CD||No current abscess only Current or past low simple fistula Current or past high complex fistula|
|Stenotic CD||Current or past small bowel stenosis Current or past large bowel stenosis Current or past anastomotic stenosis|
|Medically induced remission of CD||CDAI ≤ 150 No current abscess No current fistula No previous intestinal surgery|
|Surgically induced remission of CD||CDAI ≤ 150 No current abscess No current fistula Previous intestinal surgery within the past 5 years|
|Upper gastrointestinal CD||CDAI ≤ 150 Current disease location upper GI Initial disease location upper GI|
|Extraintestinal manifestations of CD||Pyoderma Primary sclerosing cholangitis Ankylosing spondylitis Uveitis|
Evaluation of appropriateness in SIBDCS patients
Each patient was evaluated taking his global clinical situation into consideration. In the context of the EPACT II panel, the experts rated therapies, focusing on the description of typical patients for each clinical situation envisioned. In real life, however, the clinical situation of a patient is generally more complicated, in particular for patients with long-standing illness and a complex disease course. Moreover, it proved unrealistic to extract too many details from patient records, especially on the chronological course of the disease, as we mostly assessed cases using retrospective information collected at the time of inclusion (baseline). Thus, for example, a patient may have fistulizing disease associated with an ongoing stenosis, and the given treatment has to take into account both situations, for which no formal order in the decision process can be clearly assigned. Such a situation is therefore regarded as a combination of different clinical situations. The first step in this analysis was based on the identification of the different combinations of individual clinical situations for each patient (Figure 1, step 1). If a patient satisfied the definitions and criteria for more than one clinical situation, each of these was reported and assessed separately.
As patients often receive a combination of therapies (Figure 1, step 2), the next step was to assess the appropriateness of the combination of therapies received by each patient, according to the combination of clinical situations. For this purpose, each therapy was first assessed individually using the EPACT II criteria for each clinical situation13–16 (Figure 1, step 3). We then assessed the global appropriateness of therapy for each patient, applying the following rule: if a patient received at least one appropriate treatment for one of the clinical situations, we considered that the global current therapy was appropriate. Furthermore, if the patient did not receive any appropriate drug therapy, but received at least one uncertain treatment, then the global current therapy was considered uncertain. Finally, a therapy was considered inappropriate if none of the treatments received was appropriate (or uncertain) for any of the clinical situations presented by the patient.
Three additional assumptions were made. First, a treatment was considered inappropriate for a clinical situation if it was not formally included in the EPACT II panel voting process, the reason being that the indication for this treatment in the given clinical situation, according to a high level of evidence, had not even been proposed for voting by the EPACT II panel. The second assumption related to the case of absence of any treatment. This was considered inappropriate unless a ‘wait & see’ recommendation was judged appropriate by the panel. Thus, observing the evolution of a simple fistula was considered appropriate, according to current literature evidence.17, 18 The third hypothesis related to the cases for which information on the response to past therapies was missing. In such cases, we considered the current therapy as being uncertain.
In the final analysis of appropriateness, and as is common in the application of the RAND/UCLA Appropriateness Method,19, 20 we dichotomized assessment into inappropriate and appropriate therapy, the latter also including treatments of ‘uncertain’ appropriateness.
This is a cross-sectional analysis, evaluating therapy of CD patients at baseline. Data were collected and exported from the Swiss IBD Access Databases. Analyses of proportions of appropriate treatments were performed using stata software (StataCorp, College Station, TX, USA). Wilcoxon rank sum test was used for testing differences in mean age at diagnosis and disease duration, and chi-square test was used for testing differences in proportions.
The study was approved by the respective ethics committees of the Swiss regions where patients were recruited.
Eight hundred and twenty-one CD patients were included in the cohort between November 2006 and May 2009, 51% were males and the mean age (s.d.) at enrolment was 41 years (15). We identified 288 patients (35%) with a fistulizing disease phenotype who satisfied EPACT II definitions (Table 2). Patients with fistulizing CD were diagnosed at a younger age (P < 0.001); the mean age (s.d.) at diagnosis was 27 years (11), compared with those with another disease phenotype (31 years, 15), and their disease duration was longer [14 years (10) vs. 10 (9)].
|CD patient without fistulizing disease (N = 533), n (%)||CD patient with fistulizing disease (N = 288), n (%)|
|Male||249 (46.7)||146 (50.7)|
|Female||284 (53.3)||142 (49.3)|
|Age at enrolment (years), mean (s.d.)||41.3 (16.0)||41.4 (13.0)|
|Age at diagnosis (years), mean (s.d.)||31.4 (14.6)||27.1 (11.1)|
|Duration of disease (years), mean (s.d.)||9.9 (9.4)||14.4 (9.8)|
|Type of fistula|
|Low simple fistula||59 (20.5)|
|Past fistula||44 (15.3)|
|Ongoing fistula||15 (5.2)|
|High complex fistula||229 (79.5)|
|Past fistula||151 (52.4)|
|Ongoing fistula||78 (27.1)|
|Treatment at enrolment|
|No treatment||40 (13.9)|
|Single therapy||135 (46.9)|
|Number of drugs used|
Eighty percent of patients with fistulizing disease had a high complex fistula. In 93 patients (32.3%), the fistula was draining at the time of enrolment (Table 2). The proportion of active drained fistulae varied between 25.4% for low simple fistulae and 34.1% for complex fistulae. This means that at baseline, 11.3% of the CD population of the cohort had an active fistula. Concerning global therapy at enrolment (Table 2), 14% of patients with fistulizing disease did not receive any treatment, 47% received a single drug and 39% received two to five different drugs.
Patients were selected for this study if they presented at least one fistula in the course of the disease. Nevertheless, the disease present at baseline could comprise other clinical characteristics, thus allowing inclusion in one or more other major clinical situations, based on the definitions listed in Table 1. The number of individual situations identified in combination with fistulizing CD is listed in Table 3. A total of 624 individual situations could be identified in the 288 patients with fistulizing CD. The mean number of combinations varies between 2 and 5 (mean: 2.2, median: 2), reflecting the complex disease pattern of these patients. Seventy patients (24.3%) presented a clinical situation of fistulizing CD alone. One hundred and thirty (45.1%) patients presented at least one clinical situation for both fistulizing and stenotic CD, and 28.8% had active luminal disease. A quarter of patients were in remission [Crohn's disease activity index (CDAI) below 150 points], mostly medically induced. Extraintestinal manifestations occurred in 12.2%, and upper gastrointestinal disease in 5.6% of patients with fistulizing disease.
|Fistulizing CD (Ntot = 288)||n||(N/Ntot) %|
|Associated with a combination of 1–4 of the following clinical situations|
|Active luminal CD||24||8.3|
|Medically induced remission of CD||47||16.3|
|Surgically induced remission of CD||25||8.7|
|Upper gastrointestinal CD||16||5.6|
|Extraintestinal manifestations of CD||35||12.2|
|Total number of clinical situations for fistulizing CD patients||624|
We assessed the appropriateness of therapies after evaluating all available elements from the enrolment questionnaire that could have an impact on the indication for a given treatment, for example, documented past therapies, response to the latter and possible reasons for discontinuation. In 32/624 clinical situations, the details of past treatment response were missing, leading us to attribute the label of uncertainty to these situations (see Methods). In the 288 patients, we found that 78% received a globally appropriate therapy and 22% a therapy globally assessed as inappropriate (Table 4).
|Total||Globally appropriate||Globally inappropriate|
|Fistulizing CD with active fistula||93||60||64.5||18||19.4||15||16.1|
|Low simple fistula||15||8||53.3||2||13.3||5||33.3|
|High complex fistula||78||52||66.7||16||20.5||10||12.8|
When considering patients with an active fistula at enrolment (Table 4), global therapy was less appropriate for patients having a low simple fistula than a complex fistula (67% vs. 87%, P = 0.048). The corresponding inappropriate treatments were steroids (four cases), 5-ASA compounds (three cases). In addition, eight patients suffering from active fistulizing disease and having a complex fistula did not receive any medical treatment.
Table 5 shows the most frequent therapies received by patients with fistulizing CD. This list comprises the therapies rated during the EPACT II panel. In this table, we considered appropriateness of each individual treatment according to the global clinical situation of the patient. The results thus depend on the combination of individual situations met by the patient at baseline, leading to the fact that a single treatment could either be considered as appropriate or inappropriate depending on this combination. Antibiotics and methotrexate therapy were assessed as globally appropriate in all cases and azathioprine/mercaptopurine (AZA/MP) in 96% of the cases. Anti-tumor necrosis factor α (TNFα) was given to 100 patients (34.7%). Thirty-three patients received both infliximab and AZA/MP. In 91% of cases, this therapy was considered globally appropriate. Nevertheless, 70% of cases for which anti-TNFα was given were judged uncertain and 21% were judged appropriate. The most inappropriate treatment given was 5-ASA compounds (17% of patients), which was considered globally inappropriate for 84% of the cases. It was considered globally appropriate in eight cases, corresponding to patients in surgically induced remission or with active luminal disease. A majority of steroid treatments were judged globally inappropriate. Steroids were considered globally appropriate in patients with active luminal disease, upper GI disease or extraintestinal manifestations (ankylosing spondylitis or uveitis).
|Globally appropriate||Globally inappropriate||Total (N/Ntot)|
We identified 821 Crohn’s disease patients in the SIBDCS, 288 (35%) of these patients having developed at least one fistula once in their lifetime. In about 80% of the CD patients with fistulizing disease who were enrolled in the SIBDCS, therapy was found to be globally appropriate, somewhat more in patients with active draining high complex fistulae.
Half of the patients received a single therapy and 40% received two therapies or more. The most appropriate treatments given were antibiotics, AZA/MP and methotrexate, representing 44% of all therapies for fistulizing CD patients. Anti-TNFs corresponded to 23% of all drugs given and were considered globally appropriate in the majority of cases. Therapies in most cases judged inappropriate were steroids and 5-ASA compounds.
Using questionnaires specifically designed for the SIBDCS, it was possible to assess appropriateness of care using the EPACT II criteria by collecting detailed and explicit information on disease features, including current and previous treatments. Nevertheless, this study demonstrates how difficult it is to assess appropriateness of therapy, especially in a cross-sectional study performed at baseline, where we had to take into account both history of previous therapy and course of the disease (retrospective information), and current condition and therapies (prospective information). Indeed, we encountered two major difficulties when using the EPACT II definitions and criteria. The first was linked to the EPACT II definitions used for classifying patients into major clinical situations. In fact, during the EPACT II panel process, patients were considered as presenting only one major clinical situation and each of these situations was rated independently. However, in real life, CD patients often have a polymorphic disease pattern, characterized by a combination of different clinical situations. This was the case for 76% of fistulizing disease patients in our study and it is also linked to the fact that we did not collect data on detailed chronological aspects of the course of the disease. The assessment of appropriateness was established by taking into account not only current status of fistula, but also all phenotypes over time. Thus, if a patient has had an episode of fistula, he/she was considered as having fistulizing disease. The second difficulty was that EPACT II criteria were established by rating independently the most pertinent treatments for each major clinical situation, but in the real overall clinical situation, patients often receive multiple treatments. We identified 39% of patients with more than one treatment and we thus extended the assessment of appropriateness to take into account the global situation including all therapies to reflect the complexity of these actual cases.
A previous retrospective study allowed us to demonstrate the feasibility of using medical records of CD patients to assess the appropriateness of therapy according to EPACT I criteria.20 Medical records were checked with reference to the last patient visit if this occurred within 6 months or less. This is a different process from that of taking information at baseline in a cohort study, as patients could have come for a control visit either during a remission period or during a visit motivated by worsening of the disease. In this latter case, the gastroenterologist might have decided not to enrol patients because they were too ill, thus introducing a selection bias.
Moreover, in the previous study,20 information from patient charts was collected by a physician who was aware of the EPACT definitions and criteria at the time of enrolment. In our study, neither study nurses nor the gastroenterologists were specifically aware of the assessment of appropriateness of therapy at the time data were collected, which may limit information bias in the present study compared with the results of Guessous et al.
In our study, global therapy was mostly found appropriate in fistulizing CD patients. Among patients with current fistula activity, we observed that treatment for simple fistulae was globally less appropriate than for complex fistulae. The clinician may have paid more attention to a disease pattern comprising more complaints, as complex fistulae are more often associated with abdominal pain, thus leading to more intensive or appropriate treatments.
According to EPACT II criteria, the majority of appropriate drug treatments encountered in this study were antibiotics and AZA/MP. This reflects indications found in the literature, which considered antibiotics as the first-line medical therapy for induction of fistula healing5, 14, 21 or as a treatment acting as a bridge therapy for AZA/MP. Immunosuppressants are considered a second-line treatment for patients who do not require immediate surgery and if other therapies are used in parallel. AZA/MP seems to be an effective treatment, especially for perianal fistulae. These results are also in accordance with the ECCO Statements 9G, 9J.18
Twenty-three per cent of all the given therapies were anti-TNF treatments, mostly infliximab (69%) or adalimumab (27%). Four patients were treated with certolizumab pegol, a treatment considered inappropriate according to the EPACT II criteria. Indeed, at the time of the EPACT II panel, no study had clearly shown the efficacy of certolizumab pegol for patients with fistulizing disease. Regarding infliximab and adalimumab, these treatments were rated as uncertain during the EPACT II panel, reflecting the state of knowledge at the end of 2007. However, recent studies have shown that infliximab is a highly efficacious therapy for inducing remission, which could be used also as a maintenance agent in patients with fistulizing disease.22 Thus, infliximab is currently considered an effective maintenance therapy for patients with fistulae,23 and this treatment was appropriate in case of recurrent fistulizing disease.21 The same could be observed with adalimumab, for which recent studies have shown a decrease in the number of fistulae compared with placebo, and improved fistula closure.24 Thus, this treatment might currently be considered as appropriate, because it leads to an improvement in fistulizing disease, as well as inducing a decrease in the number of hospitalizations and operations.25 As stated in the ECCO Statement 9K,18 infliximab or adalimumab should be used as a second-line medical treatment; this probably also explains why the number of patients receiving them is quite high. When considering these two anti-TNFs, assessment of appropriateness according to the EPACT II criteria seems to show a gap between the criteria and real practice, leading to uncertain treatment being considered as appropriate.
This is a limitation of the EPACT II criteria, taking into account the fact that the assessment of these treatments was established at the end of 2007, before the results of these more recent studies were known, which emphasizes the need to update EPACT criteria regularly due to the recent and rapid evolution in the treatments for fistulizing CD.
The most inappropriate treatments given were steroids and 5-ASA compounds. Steroids were given as single or combined treatment in 38 cases, of which four were related to patients with an active fistula. For these cases, the disease was considered a combination of fistulizing disease with active luminal or upper GI disease or accompanied by an extraintestinal manifestation. This may be the reason why steroids were given, even if the fistula was still active and steroids have been considered to increase complications and need for surgery in such cases.
This leads to the question of treatments, in terms of priority, according to symptoms and pain described by the patients, which is difficult to assess in a cross-sectional study. The same could be observed for 5-ASA compounds therapy, which was given in 38 cases. None of these cases could be considered appropriate according to the EPACT II criteria, apart from two where fistulizing disease was coupled with maintenance of remission induced by surgery. Generally, use of 5-ASA compounds for treatment of fistulizing disease has not proved effective,26 with the exception of post-operative maintenance of remission.
Finally, 40 patients did not receive any treatment and these cases were assessed as being inappropriate, except in the case of simple fistulae that were asymptomatic.18, 27 In fact, spontaneous healing rates of fistulae in patients with CD varies between 6% and 13% compared with patients under drug treatment,24 suggesting that patients with fistulizing CD will have relapses and that treatment is thus mostly required to prevent this complication.
In general, we could observe that the results found in this study, using the EPACT II criteria, are consistent with the statements in the updated ECCO guidelines17, 18 for the treatments for simple or complex fistulizing CD.
This study indicates that globally treatment is most often appropriate in CD patients with fistulizing disease. Our analyses also further demonstrate the feasibility of applying appropriateness criteria (EPACT II) to study one aspect of quality of care. However, the results also highlight how complex the assessment of appropriateness of therapies is in fistulizing CD patients with superimposed multiple system patterns and often several treatments. Since this evaluation was made using retrospective data with their inherent limitations, we hope that the prospective assessment of appropriateness of CD treatment will be facilitated when the Swiss IBD cohort yields prospective data from annual follow-up.
This study was carried out by all the gastroenterologists and investigators who are listed in the Appendix. We thank Susan Giddons for her support with editing. Declaration of personal interests: P. Michetti and F. Seibold have been paid lecturers or consultants for Abbott, Ferring, Schering-Plough and UCB. G. Rogler has been a paid lecturer or consultant for Abbott, Essex, FALK, Ferring, Novartis, Tillots and UCB. He has received grant support from Abbott, Ardeypharm, Essex, FALK, Flamentera, Novartis, UCB and Zeller. No other personal interests are declared. Declaration of funding interests: The study was supported by the Swiss National Science Foundation (SNSF) grant N°3347CO-108792/1 and PBLAP3-124341.
- 7The Rand/UCLA Appropriateness Method User’s Manual. MR-1269-DG-XII/RE. Santa Monica: RAND Corporation, 2001. Available at: http://www.rand.org/pubs/monograph_reports/MR1269., , , et al.
- 10Toward an integrated clinical, molecular and serological classification of inflammatory bowel disease: report of a Working Party of the 2005 Montreal World Congress of Gastroenterology. Can J Gastroenterol 2005; 19(Suppl. A): 5–36., , , et al.
- 16Appropriate management of special situations in Crohn’s disease (upper gastro-intestinal; extra-intestinal manifestations; drug safety during pregnancy and breastfeeding): results of a multidisciplinary international expert panel-EPACT II. J Crohn’s & Colitis 2009; 3: 257–63., , , et al.
Members of the SIBDCS study group
Pierluigi Ballabeni, Peter Bauerfeind, Christoph Beglinger, Stefan Begré, José Bengoa, Janek Binek, Daniel Boller, Jan Borovicka, Christian Braegger, Patrick Brun, Bernard Burnand, Rafael Camara, Dominique Criblez, Philippe de Saussure, Lukas Degen, Joakim Delarive, Tobias Ehmann, Matthias Engelmann, Ali El Wafa, Christian Felley, Alain Frei, Remus Frei, Michael Fried, Michael Friedt, Florian Froehlich, Suzanne Gallot-Lavallée, Tilman Gerlach, Martin Geyer, Marc Girardin, Oliver Goetze, Horst Haack, Serge Hediger, Peter Hengstler, Klaas Heyland, Patrick Janiak, Pascal Juillerat, Vera Kessler Brondolo, Christoph Knoblauch, Gerd A. Kullak-Ublick, Michael Manz, Rémy Meier, Christa Meyenberger, Pierre Michetti, Christian Mottet, Christoph Müller, Beat Müllhaupt, Thierry Nicolet, Andreas Nydegger, Isabelle Pache, Franziska Piccoli, Julia Pilz, Valérie Pittet, Ronald Rentsch, Jean-Pierre Rey, Silvia Rihs, Daniela Rogler, Gerhard Rogler, Markus Sagmeister, Bernhard Sauter, Niklaus Schaub, Susanne Schibli, Alain Schoepfer, Franck Seibold, Johannes Spalinger, Philippe Stadler, Michael Steuerwald, Alex Straumann, Michael Sulz, Michela Tempia-Caliera, Joël Thorens, John-Paul Vader, Stefan Vavricka, Jürg Vögtlin, Roland Von Känel, Gert Wachter, Jürg Wermuth, Paul Wiesel.