The efficacy and sustainability of a reduced risankizumab dose after achievement of low disease activity of psoriasis: a 24-week studyDear Editor,
Biologic drugs have significantly transformed the manage-ment of psoriasis due to their high efficacy, enabling many patients to achieve complete or near-complete clearance.1 While sustained treatment is recommended to maintain efficacy, continuous administration at the standard dosing regimen may lead to overtreatment for some patients.2 Dose reductions may reduce the cumulative biologic drug expo-sure, potential adverse effects, and healthcare costs.3-6 On the other hand, this approach requires individualized treat-ment with close monitoring for relapses.
Studies that report dose reductions primarily focus on TNF-αlpha and IL-12/23 inhibitors.3-7 Data on IL-23 inhibitors remain limited.8,9 Risankizumab, an IL-23 inhibitor, is rec-ommended for psoriasis at a dose of 150 mg subcutaneously at weeks- 0 and -4 and every 12-weeks thereafter. Our study aimed to evaluate the efficacy and sustainability of a reduced risankizumab dose (75 mg every 12 weeks) in patients achieving complete or near-complete clearance, and to explore factors associated with successful outcomes.
This retrospective study was conducted at a tertiary psoriasis clinic. We reviewed the patients treated with risankizumab between 2021 and 2024. The treatment was initiated according to the recommended standard dosing scheme. Eligibility for dose reduction required minimal disease activity after a minimum of 52-weeks of treat-ment, defined as absolute PASI (Psoriasis Area and Severity Index) ≤3 and inactive psoriatic arthritis for the preced-ing 24-weeks. With patient consent, the maintenance dose was reduced to 75 mg every 12-weeks.
Patients with flares (PASI score >3 and/or exacerbation of psoriatic arthritis) were escalated back to standard dosing or switched to another biologic. Demographic and clinical data included age, sex, Body Mass Index (BMI), involvement of special areas, presence of psoriatic arthritis, comorbidities, previous systemic treatments, and PASI scores at baseline, week-16, and week-52 of the recommended risankizumab dose, and at dose reduction, weeks-12 and -24 following reduced-dose maintenance treatment. PASI scores and pso-riatic arthritis activity were recorded at week-12 in patients who were switched back to the standard risankizumab dose due to relapse of skin or joint symptoms.
Continuous variables are expressed as mean ± SD, cate-gorical variables as n (%), and compared using appropriate tests. A two-tailed p < 0.05 was considered significant. The study received approval from the institutional review board (approval number: 72-2024).
A total of 21 patients (14 males, 7 females; mean age 47.5±16.7 years) were included; 7 (33.3%) had concomi-tant psoriatic arthritis. The characteristics of the patients are summarized in Table 1.
The mean PASI score at baseline was 14.3±6.2 (range 7.7-38.6). Dose reductions were made at a mean of 75.4-weeks from baseline (range 52-100 weeks), at which time the mean PASI score was 0.6 (range 0-2.4), with 47.6% of the patients having complete clearance. The PASI scores of the patients before and after dose reduction are summa-rized in Table 2.
PASI scores before and after dose reduction with comparison between groups of sustained efficacy and relapse.
Following dose reductions, loss of efficacy was observed in five patients. Two patients developed mild skin lesions that increased the absolute PASI score above 3 at weeks-12 and -24. Three patients had exacerbations of psoriatic arthritis at weeks-12 (n = 1) and 24 (n = 2), despite PASI scores of 0.
No significant differences were found between patients who sustained efficacy and those who did not in terms of age (p = 0.842), gender (p = 0.280), BMI (p = 0.333), disease duration (p = 0.398), or previous biologic experience (p = 1.00). The mean PASI scores at baseline were also similar (p = 0.062). None of the 10 patients who achieved a PASI score of 0 until dose reductions experienced relapses in skin lesions.
Of the five patients with loss of efficacy, standard main-tenance dose treatment (150 mg every 12-weeks) was reinstituted in four. In one patient, who had experienced arthritis flares, the treatment was switched to certolizumab due to plans for pregnancy. Following dose elevations, remis-sion was re-achieved in three patients. In one patient, although the PASI score could not be reduced below 3, the patient continued taking risankizumab because of mainte-nance of a PASI-75 response.
There has been growing interest in reducing biologic doses following remission of psoriatic manifestations without compromising efficacy and sustainability, with varying success rates. These variations may be partly due to dif-ferences in criteria for initiating dose reductions, dose reduction protocols, and study designs.3,4,6-11 Eligibility cri-teria for dose reductions typically included a minimum duration of standard treatment (3- to 12-months) and achievement of stable minimal disease activity for 6 weeks to 12-months, as defined by one or more of the following criteria: an absolute PASI score of ≤3, ≤5, or ≤8; relative PASI improvements (PASI-75, PASI-90, or PASI-100); or a Physicians Global Assessment (PGA) score of 0 or 1.3,4,6-11 Although most studies used relative PASI scores, we mainly utilized the absolute PASI score, as it more accurately reflects cur-rent disease severity. Absolute PASI is especially valuable in real-life settings, where baseline PASI scores are generally lower.12
Additionally, monitoring the maintenance of improve-ments following dose reductions is equally important. Most studies used the same criteria as those followed by dose reductions. This was also the case in our study. Some studies used higher absolute PASI scores (>5-8), losses in PASI 50-80-90-100 responses, an increased PGA score (≥3), and/or an increased disease activity unacceptable to the patient. Variations in these criteria may make it difficult to compare treatment outcomes.
Several studies evaluated factors affecting the mainte-nance of remission under reduced doses. Longer disease duration, higher baseline PASI, increased BMI, and conco-mitant psoriatic arthritis were factors associated with failure.4,6 Achieving PASI-100 earlier and being treated with adalimumab instead of ustekinumab and etanercept were associated with a higher success rate.3,11 In our study, gen-der, age, BMI, disease duration, PASI scores at baseline and at the time of dose reductions, and coexisting psoriatic arthri-tis did not predict dose reduction success.
In a randomized controlled trial, patients who achieved PASI-100 response at weeks 20-28 with guselkumab were assigned to receive either the standard every 8-week dos-ing or a prolonged dosing interval of every 16-weeks.8 By week 68, the two groups were similar in terms of disease control (PASI < 3) and levels of IL-17A, IL-17F, IL-22, and tissue-resident CD8-positive memory cells. These find-ings are of particular value as they demonstrate clinical and immunological disease control following prolongation of dosing intervals in patients with complete skin clear-ance with guselkumab. In our study, excellent skin response was maintained in all 10 patients after dose reductions of risankizumab following the achievement of a PASI-100 response.
The main limitations of our study include its retrospec-tive design, the limited sample size, and the lack of a control group with similar patient characteristics. Nevertheless, our findings merit consideration as they demonstrate the feasi-bility of dose reductions following complete clearance of skin lesions in real-world risankizumab treatment. Prospec-tive studies and randomized controlled trials are needed with larger patient populations.
In conclusion, following the achievement of low disease activity, reduced dose risankizumab maintained remission for at least 24-weeks in 76.2% of our patients. Of note, all patients who achieved complete skin clearance with stan-dard risankizumab treatment maintained PASI-100 status following dose reduction, suggesting that the most suitable candidates for reliable and safe dose reduction are those achieving PASI-100 response. On the other hand, the higher incidence of adverse outcomes following dose reductions in patients with psoriatic arthritis warrants caution when considering dose reductions.
Data availability statement
The entire dataset supporting the results of this study was published in this article.
Research data availability
The entire dataset supporting the results of this study was published in this article.
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Edited by
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Editor
Sílvio Alencar Marques.
