Prednisone plus sulfasalazine accelerated the improvement in disease activity in Crohn disease
ACP J Club. 1991 July-Aug;115:8. doi:10.7326/ACPJC-1991-115-1-008
Rijk MC, van Hogezand RA, van Lier HJ, van Tongeren JH. Sulphasalazine and prednisone compared with sulphasalazine for treating active Crohn disease. Ann Intern Med. 1991 Mar 15;114:445-50. [PubMed ID: 1671631]
To evaluate the effectiveness of sulfasalazine plus prednisone compared with sulfasalazine alone in patients with active Crohn disease.
Randomized, double-blind, placebo-controlled trial of 16 weeks duration.
10 Dutch hospitals.
Patients with active Crohn disease diagnosed by clinical and radiographic criteria who had a Van Hees Activity Index of ≥ 140 were included. Patients were excluded if they were severely ill; pregnant; required antibiotics, corticosteroids, or surgery; or had treatment within the preceding 4 weeks. Patients were also excluded if they had a blind loop, ileostomy, proximal colostomy, or ileorectal anastomosis; proximal or extensive small-bowel disease; an increase to > twice normal of at least 2 of 4 liver function variables; a creatinine clearance < 30 mL/min; diabetes mellitus; or a sulfa or salicylate allergy. Of 71 patients randomized, 60 (85%) completed the trial.
Patients received either sulfasalazine (6 g/d, reduced to 4 g/d if adverse effects occurred) and prednisone (30 mg/d during the first 2 weeks, then tapered by 5 mg/2 wk to 10 mg/d after 8 weeks) (n = 30), or sulfasalazine (same dose) and placebo (n = 30).
Main outcome measures
The Van Hees Activity Index and the Crohn's Disease Activity Index.
In the first 6 weeks, the Van Hees Activity Index decreased to a median of 70% (interquartile range, 57% to 80%) of the initial value in patients treated with sulfasalazine and prednisone and to a median of 87% (interquartile range, 70% to 94%) in patients treated with sulfasalazine and placebo (P = 0.001). This improvement lasted for 16 weeks; however, in the last 4 weeks of treatment, the decrease in the Van Hees Activity Index was no longer significant (sulfasalazine plus prednisone, 63%; sulfasalazine alone, 70%, P = 0.10). Decreases in the Crohn's Disease Activity Index were not significant in the first 6 weeks (P > 0.13) nor in the last 4 weeks of treatment (P = 0.19).
Treatment of active Crohn disease with prednisone in addition to sulfasalazine resulted in a markedly faster improvement in disease activity in the first 6 weeks compared with sulfasalazine alone. This difference could only be shown using the Van Hees Activity Index. This benefit remained throughout the 16-week treatment period, although it was no longer significant at the end of the trial.
Source of funding: Not stated.
Address for article reprint: Dr. M.C. Rijk, Department of Internal Medicine, Ziekenhuis de Baronie, P.O. Box 90157, 4800 RL Breda, The Netherlands.
The questions posed in this study are clinically relevant to the treatment of active Crohn disease because the synergistic effect of combined therapy compared with single drug therapy could improve quality of life in these patients.
The study design is sound. The eligibility criteria are well described, permitting readers to apply these results to similar patients in their practices. However, only one third of those screened actually entered and completed the trial. The authors carefully showed similarity in prognostic features between the 2 groups at entry. A significantly faster remission of symptoms was achieved with the combination of steroids and sulfasalazine. The sample size, however, was inadequate to show a statistically significant difference between groups in the last 4 weeks of the study or in the subgroup analysis.
The dose of sulfasalazine used in this trial was greater than that used in similar studies. Further, it is not standard practice to maintain outpatients on low-dose prednisone (10 mg/d) for 8 to 9 weeks without previous demonstration of a need for maintenance steroids. The incidence of adverse drug effects in each group was not reported except for those patients withdrawn because of treatment failure. This is an important omission when considering the dose of sulfasalazine used.
These results suggest that patients with severe Crohn disease benefit from combined therapy with steroids and sulfasalazine. If rapid remission is desirable, combined therapy is indicated. Larger studies are needed to determine whether benefit persists in the long term and occurs in all subgroups. Similar trials are also warranted using acetylsalicylic acid compounds.
Jan Irvine, MD, MSc
McMaster UniversityHamilton, Ontario, Canada