Patients with EP often have shorter biologic survival period than patients with plaque-type psoriasis. However, two reports have shown excellent and sustained treatment efficacy of guselkumab in EP [7, 8]. In our case series, not all EP patients responded well to guselkumab. The PASI 75 and PASI 90 response rates were lower in our series than in the pivotal phase III studies which included patients with plaque-type psoriasis [6, 7]. Most of our patients also showed a slower response compared with Sano’s series of EP . This lower and slower treatment response may be partly explained by the history of multiple prior biological failure in our patients [3, 9, 10] and unstable disease course due to the lack of a washout period before receiving guselkumab. However, guselkumab still showed better drug survival compared with our prior experience of other biologics in a similar population, despite more prior biologic failures [1, 2].
At week 4, two patients (15.4%) achieved more than PASI 75 improvement, including the only patient who was biologic naïve. The other early responder was treated with ustekinumab before and had no history of secondary failure. She was switched to guselkumab treatment due to the lack of ustekinumab in our hospital. These two early responders at week 4 achieved PASI 100 at week 28 (Fig. 1a). The other 11 patients (84.6%) were resistant to at least one previous biological agent (etanercept: 5 patients; adalimumab: 6 patients; golimumab: 2 patients; ustekinumab: 8 patients; secukinumab: 9 patients; ixekizumab: 4 patients), and 9 of them (69.2%) were resistant to more than one biological agent. Two, three, one, one, and two patients had failed two, three, four, five, and six prior biologics, respectively.
PASI 50 response at week 12 seems to predict long-term guselkumab drug survival. We divided the EP patients into responders and nonresponders according to their PASI response at week 12 (responders: PASI response ≥ 50 at week 12; nonresponders: PASI response < 50 at week 12). Responders (eight patients, 61.5%) showed sustained and improved effectiveness during follow-up (Fig. 1b, mean ± SD PASI improvement at weeks 4, 12, 20, 28, and 36 of 46.9 ± 27.1%, 74.7 ± 14.5%, 85.0 ± 12.7%, 85.7 ± 12.8%, and 88.8 ± 12.5%, respectively). Nonresponders showed shorter drug survival and quickly deteriorating PASI improvement after their peak response (Fig. 1b, mean ± SD PASI improvement at weeks 4, 12, 20, and 28 of 22.4 ± 31.3%, 37.0 ± 11.5%, 30.5 ± 12.5%, and 19.5 ± 21.7%, respectively).
Human leukocyte antigen (HLA)-Cw6 has been reported to affect the clinical efficacy of guselkumab in patients with moderate-to-severe psoriasis . However, none of our patients had HLA-Cw6 allele. This may partly explain the slower PASI response in our patient series. However, the effect of HLA-Cw6 positivity on the effectiveness of guselkumab for psoriasis in Asian countries remains unidentified.
The limitations of the current study include a small patient population, lack of a control group, and statistical comparison. Despite these limitations, our data still describe an important real-world experience for this rare group of patients. Further studies are needed to identify the best treatment protocol for patients with EP who have failed prior biologics.