RESEARCH LETTER
Multiple Biologics Treatment Failures in Patients with Psoriasis: A Case Series of 4 Patients
Mikkel Bak JENSEN1,2
, Nikolai LOFT1, Claus ZACHARIAE1,2 and Lone SKOV1,2
1Department of Dermatology and Allergy, Copenhagen University Hospital – Herlev and Gentofte, Gentofte Hospitalsvej 15, Hellerup DK-2900, Denmark, and 2Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark, E-mail: mikkel.bak.jensen@regionh.dk
Citation: Acta Derm Venereol 2025; 105: adv42987. DOI: https://doi.org/10.2340/actadv.v105.42987.
Copyright: 2025 © The Author(s). Published by MJS Publishing, on behalf of the Society for Publication of Acta Dermato-Venereologica. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (https://creativecommons.org/licenses/by-nc/4.0/).
Submitted: Jan 19, 2025; Accepted after revision: Feb 19, 2025; Published: Mar 9, 2025.
Conflict of interest disclosures: MBJ has no conflicts of interest to declare. LS has been a paid speaker for Eli Lilly, Janssen Cilag, and Sandoz and received research funding from the LEO Foundation. CZ has been a paid speaker for Eli Lilly, Novartis, CSL, and LEO Pharma, and has been a consultant or has served on advisory boards with AbbVie, Janssen Cilag, Novartis, Eli Lilly, LEO Pharma, UCB, Almirall, Takeda, Amgen, and CSL. LS has received research funding from Almirall, Sanofi, Bristol-Myers Squibb, AbbVie, Janssen, the LEO Foundation and the Kgl. Hofbundtmager Aage Bang Foundation and honoraria as consultant and/or speaker for AbbVie, Eli Lilly, Novartis, Pfizer, and LEO Pharma, Janssen, UCB, Almirall, Galderma, Bristol-Myers Squibb, Takeda, Stada, and Sanofi. LS has served as an investigator for AbbVie, Pfizer, Sanofi, Janssen, Boehringer Ingelheim, Incyte, Eli Lilly, Novartis, Galderma and LEO Pharma.
To the Editor,
Psoriasis affects approximately 0.14% to 1.99% of the global population (1), posing a considerable burden on patients’ physical, emotional, and social well-being. Although biologics have improved management of moderate to severe psoriasis, some patients exhibit refractory disease, estimated at around 6% (2). Although different definitions exist, treatment-refractory psoriasis is often defined as patients with treatment failure of at least 3 different biologics that act on at least 2 distinct pathways (2, 3). Treatment failures can be categorized as primary, where there is no initial response, or secondary, where there is a loss of effectiveness after an initial response. Contributing factors to lack or loss of response include genetic predisposition (4), smoking, high body mass index (BMI), metabolic or cardiovascular comorbidities (5).
Here, we present 4 cases that highlight the multifactorial challenges of psoriasis unresponsive to multiple biologics.
Case 1: A 68-year-old male with 38 years of severe psoriasis and hypertension experienced only transient improvements despite multiple systemic agents (-methotrexate, cyclosporine) and successive biologics (infliximab, ustekinumab, adalimumab, apremilast, secukinumab, ixekizumab, brodalumab, and guselkumab). Most recently, bimekizumab was introduced at a shortened interval every 4 weeks (Q4W), yielding significant skin improvement (Tables I and II) (Fig. S1A).
Case 2: A 69-year-old male had a 24-year history of severe plaque psoriasis, multiple comorbidities (hypertension, coronary artery disease, chronic obstructive pulmonary disease, psoriatic arthritis [PsA]). He was treated with numerous treatments (topical agents, phototherapy, traditional systemics, and biologics (infliximab, adalimumab, ustekinumab, etanercept, secukinumab, ixekizumab, and brodalumab), the latest being guselkumab Q4W without sustained control. Adverse reactions and limited effectiveness led to multiple therapy switches (Tables I and II) (Fig. S1B).
Case 3: A 40-year-old male with psoriasis and PsA showed partial or temporary responses to methotrexate, sulfasalazine, and subsequent biologics (adalimumab, infliximab, ustekinumab, etanercept, secukinumab, ixekizumab, brodalumab, certolizumab pegol). Additionally, tofacitinib was added and most recently combined with bimekizumab, which has led to disease control of both skin and joint symptoms (Tables I and II) (Fig. S1C).
Case 4: A 64-year-old female with severe psoriasis and multiple comorbidities (obesity, type 1 diabetes, fibromyalgia, cirrhosis) responded initially but relapsed after several biologics (adalimumab, ustekinumab, secukinumab, ixekizumab, brodalumab, infliximab, risankizumab, apremilast, risankizumab). Her most recent treatment with bimekizumab, administered at an increased interval Q4W, provided only transient efficacy (Tables I and II) (Fig. S1D).
Despite the availability of multiple biologics, some patients either fail to respond initially or lose their treatment response over time, presenting significant management challenges. Our case series documents 4 such cases, exploring the context of treatment failure. The reasons for these failures are complex, but several contributing factors have been proposed.
Studies have linked metabolic conditions, such as obesity and diabetes, to exacerbated inflammatory pathways in psoriasis, potentially reducing the effectiveness of biologics. Cases 2, 3, and 4 were obese, with case 4 also having diabetes, factors that likely impacted their treatment outcomes. Consistently, a high BMI has been linked to reduced responsiveness (6), possibly due to underdosing. This is illustrated by cases 1, 2, and 4, which achieved better responses after increasing the dosing intervals for bimekizumab and guselkumab. However, each patient had previously received infliximab, a fully weight-adjusted therapy, suggesting that underdosing alone cannot fully account for the lack or loss of treatment response.
Temporary improvements followed by quick relapses in cases 1 and 4 may indicate immunogenic responses, where the development of neutralizing antibodies negates the effects of biologics. This underscores the need for improved tools to monitor and manage such immunogenicity.
A history of multiple biologic therapies, particularly among those switching between drug classes due to inadequate responses, tends to correlate with lower success rates in subsequent treatments. However, emerging insights suggest that switching within the same drug class can still be effective, highlighting the nuanced role of individual patient factors in treatment outcomes (7).
Furthermore, the presence of PsA complicates treatment, as it often requires strategies that simultaneously target both joint and skin symptoms, necessitating tailored therapeutic approaches (8). Our study includes case 3, in which the patient was successfully treated with a combination of an interleukin-17 inhibitor (bimekizumab) and a Janus kinase 1 and 3 inhibitor (tofacitinib) without additional adverse events.
These cases highlight the complexity of treating psoriasis in patients with multiple biologics failures. A multifactorial approach that considers genetic predispositions, comorbidities, and potential immunogenicity is crucial. Future research should aim to identify predictive factors that can guide personalized treatment approaches.
ACKNOWLEDGEMENT
Funding sources
This work was supported by the LEO Foundation grant number [LF-ST-21-500002] and Copenhagen University Hospital – Herlev and Gentofte Hospital, Denmark.
REFERENCES
- Parisi R, Iskandar IYK, Kontopantelis E, Augustin M, Griffiths CEM, Ashcroft DM. National, regional, and worldwide epidemiology of psoriasis: systematic analysis and modelling study. BMJ 2020; 369: m1590. https://doi.org/10.1136/bmj.m1590
- Loft N, Egeberg A, Rasmussen MK, Bryld LE, Nissen CV, Dam TN, et al. Prevalence and characterization of treatment-refractory psoriasis and super-responders to biologic treatment: a nationwide study. J Eur Acad Dermatol Venereol 2022; 36: 1284–1291. https://doi.org/10.1111/jdv.18126
- Mason KJ, Alabas OA, Dand N, Warren RB, Reynolds NJ, Barker JNWN, et al. Characteristics of ‘super responders’ and ‘super nonresponders’ to first biologic monotherapy for psoriasis: a nested case-control study. Br J Dermatol 2024; 190: 441–444. https://doi.org/10.1093/bjd/ljad446
- van Vugt LJ, van den Reek JMPA, Coenen MJH, de Jong EMGJ. A systematic review of pharmacogenetic studies on the response to biologics in patients with psoriasis. Br J Dermatol 2018; 178: 86–94. https://doi.org/10.1111/bjd.15753
- Hjort G, Schwarz CW, Skov L, Loft N. Clinical characteristics associated with response to biologics in the treatment of psoriasis. JAMA Dermatol 2024; 160: 830–837. https://doi.org/10.1001/jamadermatol.2024.1677
- Schwarz CW, Loft N, Rasmussen MK, Nissen CN, Dam TN, Ajgeiy KK, et al. Predictors of response to biologics in patients with moderate-to-severe psoriasis: a Danish nationwide cohort study. Acta Derm Venereol 2021; 101: adv00579. https://doi.org/10.2340/actadv.v101.351
- Bokor-Billmann T, Schäkel K. No need to change the drug class: ixekizumab- following secukinumab-therapy in -psoriasis. J Dermatolog Treat 2019; 30: 216–220. https://doi.org/10.1080/09546634.2018.1506081
- Yiu ZZN, Mason KJ, Hampton PJ, Reynolds NJ, Smith CH, Lunt M, et al. Drug survival of adalimumab, ustekinumab and secukinumab in patients with psoriasis: a prospective cohort study from the British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR). Br J Dermatol 2020; 183: 294–302. https://doi.org/10.1111/bjd.18981