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Early Biologics Benefit Inflammatory Bowel Disease


 

EXPERT ANALYISIS FROM A RHEUMATOLOGY SEMINAR

SANTA MONICA, Calif. – Gastroenterologists seem to be taking a page from the rheumatologists’ playbook and are starting patients with inflammatory bowel disease on a biologic agent much sooner after diagnosis than has been standard practice.

By doing so, they hope to improve the natural history of the disease, just as rheumatologists have done in rheumatoid arthritis patients, according to Dr. Russell D. Cohen, who spoke at a rheumatology seminar sponsored by Skin Disease Education Foundation (SDEF) and the University of Louisville.

Arthritis and inflammatory bowel disease (IBD) have more in common than the drugs used to treat them. Arthritis is the most common extraintestinal manifestation of IBD. Onset of joint symptoms may precede the onset of IBD, develop in parallel to it, or be unrelated, he said.

Arthritis is most likely to occur in IBD patients who have other extraintestinal manifestations such as dermatologic, ocular, or renal symptoms. The most commonly involved central joints are in the spine, where the arthritis takes the form of ankylosing spondylitis or sacroiliitis. Peripheral joints can develop arthropathies in IBD as well. About 5%-20% of IBD patients get arthritis. The cartilage and bone usually are spared from destruction. Arthritis in IBD usually involves five or more joints and lasts about 3 years.

The incidence of IBD in rheumatoid arthritis is not well defined. One of the few studies to address this question involved a review of the data sets from two large insurance companies involving 17 million people. The researchers found that the prevalence of IBD was about 0.62%-0.65% and the prevalence of RA was about 0.98%-1.08% in patients aged 47-56 years old living in the Midwest or the South. The odds ratio of having both IBD and RA was 2.1-2.7, and of having IBD and ankylosing spondylitis, about 5.8-7.8 (Inflamm. Bowel Dis. 2008;14:738-43).

The advent of biologics has changed the natural history of ulcerative colitis (UC). But before these agents became available, data from a Danish study showed that during the first year after diagnosis, 10% of UC patients lost their colon, about 23% had lost their colon after 10 years, and 31% had lost their colon 18 years out (Gut 1985;26:158-63).

In the prebiologic era, the natural history of Crohn’s disease also was grim. The disease followed an inflammatory path for the first 5 years, then became penetrating with fistula formation between years 5 and 10 in a subset of patients; stricturing could develop after year 10 (Inflamm. Bowel Dis. 2002;8:244-50).

In the past, "virtually all Crohn’s disease patients relapsed and most required one or more surgeries," said Dr. Cohen, who is codirector of the inflammatory bowel disease center at the University of Chicago. He noted that there was a 70% probability that Crohn’s would recur over a 10-year period (Gastroenterology 1985;88:1826-33).

An estimated 10% of Crohn’s patients had their colons removed surgically within 1 year of their diagnosis with IBD, and an estimated 70% of patients who had one surgery for Crohn’s would require another. The disease tended to recur at the site of anastomosis of the previous surgery and to involve as much bowel as had been removed in the previous surgery. About half of the patients needed a second surgery.

Even today, most ulcerative colitis patients are treated with steroids and many of them become steroid dependent. Findings from a study of 63 UC patients placed on steroids showed that at the end of 1 month, 34 achieved complete remission, 19 had a partial remission, and 10 had no response. Follow-up data at 1 year showed that 31 had a prolonged response, 14 were steroid dependent, and 18 needed surgery (Gastroenterology 2001;121:255-60).

These days, there is a move away from making steroids the first drug in the treatment regimen and instead starting with a biologic and adding a steroid only if necessary.

There is some overlap between the biologics used to treat rheumatologic diseases and those used to treat IBD. Recent data show that infliximab in combination with azathioprine induced a steroid-free clinical remission in 44 of 64 patients. In the same study, infliximab plus placebo induced remission in 37 of 65 patients, and azathioprine plus placebo induced remission in 21 of 75 patients. All of the patients had active IBD with a C-reactive protein level of 0.8 mg/dL or higher and lesions that were visible on endoscopy (N. Engl. J. Med. 2010;362:1383-95).

Skin Disease Education Foundation and this news organization are owned by Elsevier. Dr. Cohen disclosed financial relationships with Abbott Labs, Axcan Pharma, Elan, Centocor, Procter & Gamble, Prometheus Laboratories, Salix, Shire, UCB, and Warner Chilcott.