Does previous use of tumour necrosis inhibitors change the therapeutic effect of interleukin (IL)?17 or IL?12/23 inhibitors on psoriasis and psoriatic arthritis? Results of a systematic review

We conducted a systematic review to investigate the therapeutic effect of interleukin (IL)-17 and IL-12/23 inhibitors in patients with psoriasis (PsO) or psoriatic arthritis (PsA) who were intolerant of or had responded inadequately to tumour necrosis factor inhibitor (TNFi) therapy. We found that IL-17A and IL-12/23 inhibitors still had efficacy in patients with PsO or PsA TNFi-failed or intolerant; however, the efficacy was lower than that in TNFi-naïve patients.

AbstractBackground

Tumour necrosis factor inhibitors (TNFi) were the first biologics approved for the treatment of psoriasis (PsO) and psoriatic arthritis (PsA). However, some patients are intolerant of or unresponsive to TNFi.

Aim

To investigate the therapeutic effect of interleukin (IL)-17 and IL-12/23 inhibitors in patients with PsO or psoriatic arthritis PsA who were intolerant of or had responded inadequately to TNFi therapy (TNFi-experienced patients).

Methods

A systematic review of randomized controlled trials searched from the PubMed, Cochrane Library and Embase databases was conducted on 17 May 2021. Responses of 75% and 90% improvement on Psoriasis Area and Severity Index (PASI75, PASI90), 20%, 50% and 70% improvement on the American College of Rheumatology response criteria (ACR20, ACR50, ACR70), and full resolution of dactylitis/enthesitis were used to assess the treatment efficacy.

Results

In total, 7 studies with a total of 3398 patients with PsA were included, 1330 of whom were intolerant of or had responded inadequately to TNFi. All studies were categorized as having low risk of bias. For IL-17A inhibitors, there were significantly higher achievements in all of the endpoints compared with placebo, but the proportions of patients achieving these endpoints were lower in TNFi-experienced patients compared with TNFi-naïve patients. However, the differences between TNFi-experienced and TNFi-naïve patients were significant only for ACR responses and for full resolution of enthesitis. For IL-12/23 inhibitors, only the results for ACR20 response were reported. Significantly more TNFi-experienced patients achieved ACR20 response compared with patients receiving placebo, and the differences in treatment efficacy between TNFi-experienced and TFNi-naïve patients was not significant.

Conclusion

IL-17A and IL-12/23 inhibitors still had efficacy for patients with PsO or PsA had failed or were intolerant to TNFi therapy; however, the efficacy was lower than that in TNFi-naïve patients. Further studies to confirm these findings are warranted.