Commentary: Trajectories and Prognosis after Discontinuation of Biologics due to Remission in Psoriasis – A Nationwide Cohort Study

After achieving clinical remission or a clear or almost clear skin response for a while, both patients and dermatologists consider the possibility of stopping treatment. Unfortunately, real-world data on the maintenance of response after treatment discontinuation is lacking.

The present study investigated epidemiological characteristics and disease markers during the first two years following cessation of biologic therapy due to remission in adult patients from the Danish psoriasis registry DERMBIO, treated with biologic therapy between January 1, 2007, and December 31, 2016. Patients were considered in remission if they discontinued treatment with ‘‘remission’’ stated as the reason by their dermatologist and a PASI<3 at the time of cessation.

From a total of 3,844 treatment series, only 40 (1%) were discontinued due to remission and were compared to the rest of the 3804 (99%) treatment series. Of the patients who discontinued treatment, the median (IQR) treatment duration was 681 days (336-1419), 60% were bio-naıve (60%), and 18% had a diagnosis of psoriatic arthritis. Notably, 70% were treated with TNF inhibitors and 30% with ustekinumab. No patients were being treated with IL-17 inhibitors (or IL-23 inhibitors, in this case, because there were no IL-23 inhibitors approved during the study period). When treatment was discontinued, 24 (60%) had a PASI=0.

After two years of discontinuation, 17 (43%) remained in remission or initiated topical therapy only. This proportion of patients was slightly higher (50%) in the group of patients who were PASI = 0 at discontinuation and lower in those (31%) who were PASI>0. This suggests that maintenance of clinical remission or a very low disease activity is more likely when biologic treatment is discontinued in patients with no clinical disease activity.

Of the patients who needed to restart biological therapy (18), 13 (72%) started the same drug that had previously been discontinued, apparently with a good response, suggesting that interrupting biologic treatment due to disease remission does not increase the risk of loss of efficacy when restarting the same agent.

An essential piece of information that is lacking is how long patients were in remission (on-drug) before discontinuing biological treatment. We may expect patients in remission for a more extended period to be more likely to maintain that disease state.

This study needs to be interpreted with caution mainly due to the low number of analyzed patients (only 1% of patients (40) discontinued their treatment due to remission) and for including only patients being treated with TNF inhibitors and ustekinumab. In fact, this is a significant limitation (explained by the fact that only patients treated with biologics until December 31, 2016, were included). IL-23 inhibition has been associated with a sustained clinical response for several months after withdrawal of treatment, probably related to the potential mechanistic effects on tissue-resident memory cells and T-regulatory cells, so it will be essential to make this kind of analysis in patients treated with these therapies. Thus, in the future, it will be important to complete a follow-up study including patients treated with IL-17 inhibitors, but especially IL-23 inhibitors.

From a practical point of view, there are three critical questions when thinking about discontinuing biologic treatment:

1. In which patients should we consider discontinuing biologic treatment? The ones that have achieved skin clearance, or is it enough to be almost clear?
2. When to interrupt? As soon as remission is achieved or how long after remission is achieved?
3. Which biologic therapies are more likely to be associated with a longer period of remission after discontinuation?

This study only partially answers these questions.

In summary, this study suggests that there are patients for whom we can consider discontinuing biological treatment. They will still maintain long-term control of their disease, especially those who achieved complete skin clearance. Nevertheless, we still need more data to adopt this attitude in our clinical practice.