Dear Editors, Ixekizumab is an effective IL-17A monoclonal antibody for moderate to severe plaque psoriasis but is not curative, and recurrences are frequent following the discontinuation of anti-IL-17 therapy.1, 2 Once complete remission is achieved, the therapeutic objective should be to maintain the disease in minimal or absent activity (MDA), with treatment optimization emerging as a promising cost-efficient long-term strategy.3 While dose reduction has been shown to be a feasible approach for anti-TNF inhibitors and ustekinumab, evidence for ixekizumab remains limited regarding the optimal approach and patient selection.4, 5 We conducted a retrospective, real-world, multicenter study involving patients with plaque psoriasis who were initially treated with ixekizumab at the standard dosage (SD) and subsequently underwent treatment optimization by extending the dosing interval between January 2017 and September 2024. All patients had received at least six months of SD, achieved MDA prior to optimization, and had a minimum follow-up of six months under the tapered regimen. This ensured that patients received multiple optimized doses, allowing sufficient time to assess flares, defined as a Psoriasis Area and Severity Index (PASI) > 3 and/or a Disease Activity Index for Psoriatic Arthritis (DAPSA) > 14 in patients with concomitant PsA.3, 6 Super responders (SR) to SD were defined as those achieving PASI 0 within 16 weeks.7 Our objectives were to describe the proportion of patients who maintained MDA, determine the maximum dosing interval achieved, and identify predictive factors associated with successful treatment optimization. A total of 82 out of 446 patients (18.38%) who received ixekizumab at SD underwent down-dosing after a median of 14 months (interquartile range, IQR 9 - 26) of treatment at SD. As optimization represents an off-label approach, it was only attempted in selected patients while the remaining continued on SD either due to physician decision, patient preference, or insufficient stability of disease control. Baseline data are shown in Table 1. PASI 100 was achieved by 90.24% of patients before dose tapering, with 74.24% being SR. The most frequent initial interval extension was 6 weeks (57.31%, n = 47). Further optimization was performed in 29.26% (n = 24) of patients to intervals of ≥8 weeks. Patients who tolerated optimization experienced a slight increase in PASI while maintaining MDA (Figure 1). BMI, mean (SD) BMI ≤ 24.9 (%) BMI 25 – 29.99 (%) BMI ≥ 30 (%) 27.41 (4.70) (n = 73) 36.98 (n = 27) 33.78 (n = 25) 28.37 (n = 21) 27.42 (4.30) (n = 54) 37 (n = 20) 35.18 (n = 19) 27.77 (n = 15) 28.87 (5.60) (n = 19) 36.84 (n = 7) 31.57 (n = 6) 31.57 (n = 6) 0.52 0.94 During the first optimization attempt, 23% (n = 19) of patients flared (63.15% cutaneous and 36.84% PsA) after a median of 15 months (IQR 8.5–18.5), mostly occurring during the first extended-interval dosing regimen (Figure 2). Patients who flared had a higher prevalence of concomitant PsA (36.84% vs. 15.48%, p = 0.048), lower rates of complete response prior to tapering (78.3% vs. 95.12%, p = 0.032), and a reduced proportion of SR (44.44% vs. 78.84%, p = 0.006). No other significant baseline differences were observed, including disease duration or PASI at ixekizumab initiation between groups. Upon reintroduction of SD, disease control was reestablished in 79% of patients (n = 15). In contrast, 21% (n = 4) did not achieve disease control; of these, two cases were due to PsA and two were attributed to cutaneous flare. No serious adverse events were observed during treatment with ixekizumab, whether at the SD or during the dose tapering regimen. In our study, ixekizumab was successfully optimized in 77% of patients, surpassing the success rates reported for anti-TNF alpha and ustekinumab, and comparable to those with secukinumab.8 The most common initial dose reduction was extending the administration interval to every 6 weeks. Nevertheless, a third of patients could optimize to intervals of ≥ 8 weeks during follow-up maintaining MDA. Few predictive factors for biologic therapy optimization have been reported, including the absence of PsA, bio-naïve patients, and SR.5 Our findings align with previous reports, reinforcing SR as the strongest predictor of successful optimization. Regarding demographic characteristics, no differences were found between groups. Older patients have been described as less likely to tolerate secukinumab optimization, but ixekizumab demonstrated consistent tolerability regardless of age.8 Similarly, a higher BMI has been associated with disease recurrence during anti-TNF and ustekinumab therapy optimization, as well as with poorer response to anti-IL-17 therapy.9 Nevertheless, no such correlation was found in our study, neither in overweight nor in obese patients. Finally, the involvement of special areas did not appear to increase the risk of flare.5 In conclusion, this real-world study demonstrates that ixekizumab can be safely optimized in patients with plaque psoriasis, particularly in SR without PsA. Optimization offers a cost-effective treatment strategy by reducing the number of doses required to six to eight annually, thereby lowering costs and potentially minimizing drug-related risks. Clinicians should be aware that relapse rates increase after the first year, necessitating close follow-up. In the event of a flare, reintroducing SD should restore disease control. The main limitations of this study include its retrospective design, relatively small sample size, lack of data beyond two years, and an imbalance in patient recruitment across centers. This imbalance reflects the real-world nature of the study, as the decision to attempt optimization depended on local psoriasis unit protocols and the financing policies of each hospital pharmacy. Josep Riera-Monroig received fees for consultancy and/or as a speaker and/or for travel and/or has participated in clinical trials sponsored by Abbvie, Almirall, Amgen, Boehringer Ingelheim, Bristol-Meyers Squibb, Gebro, Isdin, Janssen, LEO Pharma, Lilly, Novartis, Pfizer, LaRochePosay, Sanofi, and UCB. Josep Manel Fernández-Armenteros received fees for consultancy and/or as a speaker and/or for travel and/or has participated in clinical trials sponsored by Abbvie, Almirall, Amgen, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Ferrer, Gebro, Isdin, Janssen, LEO Pharma, Lilly, Mylan, Novartis, Pfizer, Sanofi and UCB. Tamara Gracia-Cazaña received fees for consultancy and/or as a speaker and/or for travel and/or has participated in clinical trials sponsored by Abbvie, Almirall, Amgen, Boehringer Ingelheim, Bristol-Meyers Squibb, Janssen, LEO Pharma, Lilly, Novartis, Pfizer, Sandoz, Sanofi, and UCB. Rosa Fornons Sirvent received fees for consultancy and/or as a speaker and/or for travel and/or advisory board for Bristol Myers Squibb, UCB, Abbvie, Almirall, Bristol Myers Squibb, Ferrer, Johnson&Johnson, Leo Pharma, Lilly and Novartis. The other coauthors do not have conflicts of interest to declare.
Ceravalls et al. (Sat,) studied this question.