This study shows that although immunosuppressants were initiated much earlier during the course of CD, the need for intestinal resection remained stable over 25 years. The percentage of patients requiring intestinal surgery each year remained equal. The probability of having a definitive stoma appeared also to be unaffected from 1978 to 2002. However, large intestinal resections became more unusual.
This study has some limitations. Firstly, the retrospective nature of the study may have led to bias in the interpretation of the data—however, it was necessary to obtain an observation period long enough to ascertain the long term effect on surgery of changes in the medical strategy of CD. In addition, intestinal resection can be considered as an unbiased and solid criterion, even retrospectively, as it is performed only when necessary. Besides, during a period of 20–25 years, many factors other than the treatment strategy may have influenced the indications for surgery. However, all patients seen from the beginning were followed up in the same unit by the same small group of physicians, who used homogeneous guidelines and took collegial decisions. Moreover, comparison of cohorts at inclusion showed that they were very similar regarding demographic characteristics and disease location. In particular there is no reason to believe that CD became more severe with time while other disease characteristics did not change. Secondly, it should be noted that a relatively large proportion of patients were lost to follow up. We made no attempt to contact the patients or physicians to update the data. We do not believe this may have minimised the need for surgery of the oldest cohorts because patients who are lost to follow up are usually those doing well and not requiring further surgery. The cumulative probability of surgery in our patients was very similar to those reported in two unbiased and complete series of the literature, the NCCDS17
and the Copenhagen County cohort study.18
Finally, our unit is a tertiary referral centre and referral bias is unavoidable. To limit this bias, we restricted the analysis to patients seen during the first three months of the disease course. This precaution was not sufficient to eliminate such a referral bias because an important proportion of these patients came to surgery during that period. However, when we excluded these latter patients, analyses gave similar results and, in particular, the discrepancy between an increased use of immunosuppressants and a stable need for surgery remained unchanged. These results were confirmed in a second large group of patients.
The occurrence of stricturing and perforating complications was the main reason for excisional surgery. The frequency of these complications did not change significantly from one cohort to another. This is a disappointing result because it could be expected that immunosuppressants could have an anatomic effect and prevent these complications. Indeed, D’Haens et al
reported that in 74% of patients with colonic or ileocolonic disease who were clinically responders to azathioprine, endoscopic lesions had healed completely or nearly completely after a mean of two years of treatment. Histologically there was disappearance of the inflammatory infiltrate, with only a degree of architectural disturbance remaining.19
In the present study there was, over the most recent years, a clear decrease of intestinal resection for medical failure, which represented only 13% of surgical indications in the 1998–2002 cohort. This result may be related to immunosuppressants, but also to infliximab even though it was used sparingly in very few patients. In any case, the absence of a decrease in the need for surgery over the last 25 years questions the efficiency of our medical strategy. In fact, there is the possibility that in this study immunosuppressants had no impact on complications and the need for surgery because they were given too late during the course of the disease. Supporting this hypothesis, a large majority of patients came to surgery while not having received immunosuppressants, or were operated on early (within the first three months), while the mean time of response to purine analogues is three months.20
By contrast, if we make the hypothesis that immunosuppressants are able to change the natural history of CD, nearly half the patients who were operated on more than three months after diagnosis could have avoided surgery. Thus we can extrapolate that in our series immunosuppressants were given too late and too scarcely to have a significant impact on the need for surgery. Such an assertion is not in accordance with the anatomic effect observed by D’Haens et al
that immunosuppressants, even when given early, may have no preventive effect on the occurrence of stricturing and penetrating complications.
An interesting and more encouraging result of our study was the decrease of the probability of having a large intestinal resection over the last 25 years in the group of referred patients. A similar trend, although not significant, was observed in patients who were seen early after diagnosis and were, for the most part, operated on in our surgical unit. The reason for such a decrease, from 29% to 12% five years after diagnosis, may be linked to a greater use of immunosuppressants, but may also be a change in the surgical strategy favouring segmental and limited resections in the most recent years.
In summary, this study shows that immunosuppressants have been used increasingly over the years. However, this evolving therapeutic strategy was not associated with a decrease in the need for surgery or in a decrease of the occurrence of intestinal complications. This result does not question the efficacy of immunosuppressants for achieving and maintaining remission,21
and improving quality of life, but it does questions the timing of starting immunosuppressants in patients with moderate to severe Crohn’s disease.