Dr William J. Sandborn discussed how the roles of biologics and small molecules are evolving in the management of moderate to severe inflammatory bowel disease (IBD).1 First discussed was treatment sequencing. With regard to ulcerative colitis (UC), in a network meta-analysis, infliximab and vedolizumab achieved the highest rates of clinical remission and endoscopic improvement in patients receiving first-line therapy. For second-line therapy, the most effective agents were tofacitinib and ustekinumab. In this setting, tumor necrosis factor (TNF) blockers and vedolizumab have proved less effective at inducing clinical remission and endoscopic improvement.2 As for head-to-head trials, in the VARSITY trial, vedolizumab proved superior to adalimumab for the treatment of active UC over the course of a year.3
With regard to safety, TNF blockers are associated with granulomatous infections, serious infections, non-Hodgkin lymphoma, and demyelination (Table 1). Tofacitinib is linked to serious infections, pulmonary embolism, deep vein thrombosis, and hyperlipidemia. Importantly, vedolizumab and ustekinumab do not cause these complications.
Table 1.
Safety Considerations
| Infliximab | Adalimumab | Vedolizumab | Ustekinumab | Tofacitinib | |
|---|---|---|---|---|---|
| Granulomatous infection | + | + | − | − | − |
| Serious infection | + | + | − | − | + |
| Herpes zoster | − | − | − | − | + |
| Non-Hodgkin lymphoma | + | + | − | − | ? |
| Demyelination | + | + | − | − | − |
| DVT/PE | − | − | − | − | + |
| Hyperlipidemia | − | − | − | − | + |
DVT, deep vein thrombosis; PE, pulmonary embolism. Adapted from Sandborn WJ. Positioning biologics and small molecules in the management of moderate to severe IBD. Presented at: 2020 Virtual Advances in Inflammatory Bowel Diseases Conference; December 9-12, 2020.1
Dr Sandborn proposed an algorithm for treating moderate to severely active UC. For mild to moderate disease, treatment with mesalamine, rectal therapies, and perhaps corticosteroids is the approach of choice. For moderate to severe disease, the algorithm includes first- and second-line therapies. With first-line therapies, the clinician should consider whether extraintestinal manifestations are present, in which case an anti-TNF agent may be appropriate. If the disease is primarily in the gut, then vedolizumab may be best because of its safety profile.
In the treatment of Crohn’s disease (CD), the absence of approved Janus kinase inhibitors means the choice is among infliximab, adalimumab (both anti-TNF agents), vedolizumab, and ustekinumab. In the first-line setting, outcomes have been strongest with the 2 TNF blockers. In the second-line setting, however, ustekinumab has demonstrated the greatest efficacy, with a narrow confidence interval. With regard to safety considerations, again vedolizumab and ustekinumab have proved safer than TNF blockers.
In a study presented at United European Gastroenterology Week Virtual 2020, clinical remission (Crohn’s Disease Activity Index score <150) was achieved with ustekinumab in patients who had not previously received a biologic drug and those who had previously failed biologic treatment. The anti-interleukin (IL) 23 drug guselkumab demonstrated a slight advantage over ustekinumab in attaining clinical remission.4 This comparison will proceed to a phase 3 investigation.
As with UC, the positioning of therapies for CD begins with a determination of whether the disease is mild to moderate or moderate to severe. In the former case, the appropriate treatment may be budesonide or corticosteroids. In the latter, efficacy must be weighed against side effects. Patients who are particularly risk-averse may prefer vedolizumab or ustekinumab, even in the first-line setting (Figure 1).5
Figure 1.
Proposed algorithm for positioning therapies for patients with high-risk Crohn’s disease. TNF, tumor necrosis factor. Adapted from Nguyen NH et al. Clin Gastroenterol Hepatol. 2020;18(6):1268-12795 and Sandborn WJ. Positioning biologics and small molecules in the management of moderate to severe IBD. Presented at: 2020 Virtual Advances in Inflammatory Bowel Diseases Conference; December 9-12, 2020.1
Dr Sandborn also highlighted decision support tools for UC and CD. In the case of UC, research has shown that patients who have a longer duration of disease (>2 years), have never received an anti-TNF agent, had moderate as opposed to severe baseline endoscopy findings, and have normal albumin levels are most likely to respond to anti-integrin therapy with vedolizumab.6 In the case of CD, response and remission rates are better in patients without previous surgical resection, anti-TNF treatment, or fistulizing disease, with normal albumin levels, and with relatively low C-reactive protein levels.7
References
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