Ustekimumab for IBD: Long-Term Safety and Efficacy Data


The rationale for treating inflammatory bowel disease with ustekimumab based on more recent safety and efficacy data demonstrated by a trial that followed patients for up to 5 years.

Stephen Hanauer, MD: One of the problems we’ve had with TNF inhibitors when we institute therapy with them, both induction and maintenance, is by the end of the year, whether it’s infliximab or adalimumab, nearly 50% of patients are already off therapy. There are a few potential reasons for that. First and foremost, we’re starting effective treatment too late in that population. But nevertheless, we’re still stuck with a significant proportion of patients with a time-limited duration of disease. Now, most recently we’ve seen some publications with ustekinumab, with data out to 3 or even 5 years about potential durability. What do you think about those data with ustekinumab?

Marla Dubinsky, MD: This again goes to the sprint vs marathon discussion we were having. When we think about durability, everyone needs to understand that if a patient is in remission at 6 months, the chances are no matter what drug you use, even with the TNFs, if you remember originally with adalimumab and the CHARM data we looked at, if you got to 6 months, the chance of you dropping off at a year and then you go into your open label, was low. Once you make it past a certain point, especially out to the end of the year, and then you go into these long-term extension trials, the chance of you falling out because of ineffective therapy is low. I look at all durability sort of the same. I view that, unless there’s a safety reason that over time you get more safety issues, and that may be a TNF issue, to be fair; the advantages with vedolizumab and ustekinumab, the durability is driven also by the safety, not just that there’s lower immunogenicity and maybe you’re not using a combination as much. Whatever, if we don’t have a SONIC-like [combination] in these drugs I understand, but the lack of immunogenicity compared to TNFs, the ability to maybe use it as monotherapy, people aren’t getting as many infections, things that cause you to stop TNF, that’s the way I’m looking at the durability data from the other 2 therapies.

Stephen Hanauer, MD: Marla, in addition to the long-term efficacy data with ustekinumab in both ulcerative colitis and now in Crohn Disease going out to 5 years, we’ve seen the persistence of benefits, but what about the safety profile over the duration of up to 5 years with ustekinumab?

Marla Dubinsky, MD: Remember we first had 3-year data, and we were very excited about the safety profile, and now we have it for another 2 years, another safety cut. The infection rates are around the same, about a 4% serious infection rate. There was no surprises. We concluded the same as what we concluded, interestingly, after a year of a trial and then 3 years, and 5, which is great. It means that we continue to have faith in the safety of ustekinumab.

Stephen Hanauer, MD: I also would mention that getting rid of the concomitant therapies such as steroids and immunosuppressives on a long-term basis can help to improve the safety profile as well.

Marla Dubinsky, MD: As you noted, we don’t have controlled randomization, monotherapy vs combination, but if indeed based on SONIC, the combination may be advantageous because of its reduction in maybe immunogenicity, or increasing the drug concentrations, as has been looked at, again post hoc. But that’s where some of the discussion was, is that if these therapies have lower immunogenicity compared to anti-TNFs, is there really an advantage of adding a thiopurine, for example? That is something we need to continue to message out, that it appears that the safety profile may be improved by needing to use a thiopurine or methotrexate.

Stephen Hanauer, MD: Indeed, in those long-term data, the majority of patients who were in remission were in steroid-free remission as well. That combines to the statements that we were both making.

Marla Dubinsky, MD: We can’t underestimate the impact of corticosteroids. When you look at the role of combination therapy, a lot of patients are also on corticosteroids. Are we looking at the right thing? That adds to this idea that we need to be able to get patients off steroids and minimize the use of immunosuppressants if we can and keep our patients in deep remission.

Transcript Edited for Clarity

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