New Brodalumab Psoriasis Outcome Data Suggests That Intermittent Treatment Is As Effective as Continuous Dosing

Is It Time To Re-evaluate Our Treatment Regimens?

P. Babakinejad; P.J. Hampton

Disclosures

The British Journal of Dermatology. 2020;183(6):984-985. 

When biological drugs were first introduced for psoriasis, many guidelines suggested cessation of therapy once target outcomes were achieved. Perhaps unsurprisingly, treatment cessation led to rapid relapse in many patients. Also, on resuming treatment some patients failed to recapture their initial response, possibly due to the development of antidrug antibodies (ADA). These observations led to standard treatment regimens with continuous rather than intermittent therapy (we define intermittent therapy as cessation on reaching a satisfactory outcome and resumption of treatment when required; this has also been described as stop–start, treatment as needed, withdrawal and recapture). In this issue of the BJD, Papp et al. report a randomized placebo-controlled trial of the long-term efficacy of brodalumab through 120 weeks including a successful demonstration of an intermittent treatment regimen.[1]

In the study, 222 patients received brodalumab, with 212 remaining on treatment at 12 weeks (220 received placebo). A good response to brodalumab [static Physician's Global Assessment (sPGA) score of 0/1] was achieved in 167 participants who were rerandomized at 12 weeks, with 83 patients continuing to receive brodalumab for a total of 120 weeks, and 84 patients randomized to receive placebo. After 12 weeks on placebo, 79 (94.0%) experienced recurrence of disease (defined as sPGA score ≥ 3) after a median of 56 days, and restarted treatment with brodalumab. An excellent response to retreatment was observed, similar to the initial response to brodalumab [75% improvement in Psoriasis Area and Severity Index (PASI 75) and PASI 100: 94% and 75%, respectively, at week 120]. The majority of these patients (> 90%) achieved PASI 75 within 6 weeks of retreatment.

The goal for most patients with psoriasis is to have clear skin for as much time as possible. However, many patients require treatment breaks due to other health problems, pregnancy, lifestyle factors or health economics. Therefore, it is valuable to know whether a treatment response will be recaptured after a break. Other studies assessing intermittent therapy with ixekizumab and secukinumab have shown good disease control for significant periods of time off treatment, with median time to disease recurrence ranging from 140 to 295 days, followed by good recapture of response on retreatment.[2,3] The efficacy of intermittent therapy with anti-tumour necrosis factor (TNF)-α drugs including adalimumab and etanercept has been demonstrated.[4,5] Intermittent therapy with anti-interleukin (IL)-23 antibodies (guselkumab and risankizumab) have also shown good rates of recapture.[6,7] It is important to remember that when directly comparing intermittent with continuous therapy, the continuous regimens are generally superior.

Immunogenicity is considered to be an important factor in the efficacy of biological therapies and has been assessed in several studies. In the Papp et al. study reported in this edition of the BJD,[1] a low prevalence of ADA in their patients, suggesting low immunogenicity, may explain the good rates of recapture of response after a period of treatment withdrawal. Low prevalence of ADA associated with biological therapies targeting the IL-17 pathway (including secukinumab, ixekizumab and brodalumab), has been reported previously.[8] The prevalence of ADA was similarly low in studies assessing biologics targeting IL-23: in patients receiving ustekinumab, a low prevalence of ADA (5.2%) was identified from 39 samples, 64% of which were neutralizing.[9] A similarly low prevalence of antibodies (6.6%) was noted in a study of 869 patients on guselkumab over a 1-year period.[10] The prevalence of ADA in patients receiving adalimumab has generally been slightly higher, with prevalence ranging from 8.8% to 50%.[11] In a systematic review of anti-TNF-a therapies, a significant impact on treatment response was seen in the presence of ADA. Co-adminstration of methotrexate has been shown to reduce immunogenicity.[12]

These new data demonstrate that excellent recapture of response is achievable after a break in brodalumab treatment. The option of a more intermittent treatment regimen may be appealing to some patients and would bring health economic advantages. Further studies are needed to personalize dosing regimens, possibly with patient-led dosing intervals, to determine how flexible biological therapy can be while maintaining good disease control.

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