Dermatology: Practical and Conceptual Original Article | Dermatol Pract Concept. 2025;15(4):5458 1 Elective First-Line Use of Dimethyl Fumarate in Psoriasis: Insights from an Italian Cohort Alessandro Giunta1,*, Maria Esposito2,*, Elena Campione1, Martina Burlando3,4, Giacomo Caldarola5,6, Viviana Lora7, Federico Diotallevi8, Ersilia Tolino9, Gianmarco Silvi10, Emanuele Cozzani3,4, Ruslana Gaeta Shumak1, Rosaria Fidanza11, Paolo Antonetti11, Lorenzo Maria Pinto5,6, Valentina Mirisola12, Maria Concetta Fargnoli2, Luca Bianchi1, Francesca Prignano10 1 Dermatologic Unit, Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy 2 Department of biotechnological and Applied Clinical Sciences, University of L’Aquila, L’Aquila, Italy 3 Clinica Dermatologica, DISSAL, Università di Genova, Genova, Italy 4 Ospedale Policlinico San Martino-IRCCS, Genova, Italy 5 UOC di Dermatologia, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario A. Gemelli – IRCCS, Rome, Italy 6 Dermatologia, Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy 7 Division of Dermatology, San Gallicano Dermatological Institute, Rome, Italy 8 Dermatological Clinic, Department of Clinical and Molecular Sciences (DISCLIMO), Università Politecnica delle Marche, Ancona, Italy 9 Unit of Dermatology, Department of Medical-Surgical Science and Biotechnologies, Sapienza University of Rome, A. Fiorini Hospital, Terracina, Latina, Italy 10 Section of Dermatology, Department of Health Sciences, University of Florence, Florence, Italy 11 UOSD Dermatologia Generale ed Oncologica Ospedale San Salvatore L’Aquila ASL1 Abruzzo, L’Aquila, Italy 12 Polistudium Srl, Milan, Italy *Equally Contributed Key words: Dimethyl fumarate, Psoriasis, Systemic therapy, First-line treatment, Long-term treatment Citation: Giunta A, Esposito M, Campione E, et al. Elective First-Line Use of Dimethyl Fumarate in Psoriasis: Insights from an Italian Cohort. Dermatol Pract Concept. 2025;15(4):5458. DOI: https://doi.org/10.5826/dpc.1504a5458 Accepted: June 25, 2025; Published: October 2025 Copyright: ©2025 Giunta et al. This is an open-access article distributed under the terms of the Creative Commons Attribution- NonCommercial License (BY-NC-4.0), https://creativecommons.org/licenses/by-nc/4.0/, which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original authors and source are credited. Funding: The work was unconditionally funded by Almirall S.A. Competing Interests: M. Esposito has served as a speaker/board member for Abbvie, Almirall, Eli Lilly, Janssen, Leo Pharma, Novartis, Sanofi, and UCB. A. Giunta received grants or is an investigator for Biogen and Lilly and is a consultant/advisory board/speaker for AbbVie, Almirall, Celgene, Janssen, Leo Pharma, Eli Lilly, Merck Sharpe Dohme, Novartis, Pfizer, Sandoz, and UCB. M. Burlando served as a speaker or advisory board member for Almirall, AbbVie, Amgen, Eli Lilly, Janssen, Leopharma, Novartis, and UCB Pharma. G. Caldarola reports consulting fees or honorariums and payment for lectures from Lilly and Novartis. MC Fargnoli has served on advisory boards and received honoraria for lectures and/or research grants from AMGEN, Almirall, Abbvie, Boehringer-Ingelheim, BMS, Galderma, Kyowa Kyrin, Leo Pharma, Pierre Fabre, UCB, Lilly, Pfizer, Janssen, MSD, Novartis, Sanofi-Regeneron, and Sunpharma. Authorship: All authors have contributed significantly to this publication. Corresponding Author: Maria Esposito, MD, Dermatology, Department of Biotechnological ad Applied Clinical Sciences, University of L’Aquila, via Vetoio-Coppito 2, 67100 L’Aquila, Italy. ORCID: 0000-0002-4773-6993; E-mail: maria.esposito3@univaq.it 2 Original Article | Dermatol Pract Concept. 2025;15(4):5458 Introduction Psoriasis is a chronic inflammatory disease characterized by high prevalence and a relevant physical and psychological burden [1] often requiring systemic treatments, either with conventional or biological agents [2]. The introduction of biologicals targeting tumor necrosis factor-α (TNF-α), inter- leukin(IL)-12/23, IL-17A, IL-17RA, and IL-23 as well as the small-molecule apremilast has provided new and effective treatment options, partially reducing the use of conventional therapies [3]. However, in many countries, local guidelines recommend a stepwise approach, starting with traditional systemic therapies before initiating biological treatments [4]. The Italian SIDeMAST (Società Italiana di Dermatologia Medica, Chirurgica, Estetica e delle Malattie Sessualmente Trasmesse) guidelines recommend the use of biological ther- apies for patients with moderate-to-severe plaque psoria- sis, defined as Psoriasis Area Severity Index (PASI) >10 or body surface area (BSA) >10, or PASI <10 and BSA <10 with involvement of sensitive areas such as the face, palms, soles, nails, or genital region or in those who have shown inad- equate response or intolerance to conventional treatments [2,5]. Although the therapeutic target of new biological ther- apies is PASI 90 [6], PASI 75 remains an excellent tool for evaluating the efficacy of traditional therapies for psoriasis [7,8]. Traditional systemic treatments, including methotrex- ate (MTX), cyclosporin, acitretin, and, in Europe, fumaric acid esters (FAEs), have demonstrated moderate efficacy, with a proportion of patients achieving PASI 75 ranging from 15% to 60% [4]. Remarkably, except for FAEs, these drugs exhibit drug–drug interactions and cumulative organ toxicities [9]. Of note, the prescription of systemic drugs for psoriasis in Italy is regulated by the Agenzia Italiana del Far- maco (AIFA) and is influenced not only by the safety profile but also by approved indications and reimbursement poli- cies. MTX is one of the most widely recommended first-line systemic therapies for moderate-to-severe chronic plaque psoriasis and is particularly indicated in patients with psori- atic arthritis or systemic inflammation. With over 50 years of clinical use, it is suitable for long-term management and is supported by solid efficacy evidence [10,11]. MTX's clinical utility is reinforced by established international dosing guide- lines and consensus-based laboratory monitoring protocols [12]. However, its use is burdened by several drug interac- tions and potentially severe adverse events such as hepato- toxicity and myelosuppression [2]. Cyclosporin, on the other hand, is particularly useful for severe and rapidly progressive forms of plaque psoriasis or for cases requiring rapid disease control. It has also been used in non-plaque variants such as pustular or erythrodermic psoriasis. Its fast onset of action makes it valuable as a short-term induction therapy, partic- ularly in adults without renal or cardiovascular contraindi- cations [13]. While effective, its long-term use is limited by nephrotoxicity and other metabolic side effects [12]. Acitre- tin is mainly indicated for palmoplantar and erythrodermic psoriasis, where its systemic retinoid action provides signifi- cant therapeutic benefit. Its oral formulation and efficacy in chronic or treatment-resistant cases further support its role across various psoriasis subtypes [14]. It is contraindicated in women of childbearing potential due to its prolonged tera- togenicity [15,16]. Acitretin’s longstanding use in Europe un- derscores its utility in managing difficult-to-treat cases and Introduction: Dimethyl fumarate (DMF) is an approved conventional systemic treatment for psoria- sis that does not exhibit any drug–drug interactions or cumulative organ toxicities. Aim: This retrospective real-world study aimed to analyze the long-term efficacy, safety, and tolerabil- ity of DMF in patients with moderate psoriasis. Methods: Data on safety and efficacy were collected from medical charts. The effect on disease sever- ity was assessed using the Psoriasis Area Severity Index. Results: Our study included 148 patients over a 48-week treatment period, confirming DMF as an effective option in the treatment of moderate psoriasis. Adverse events were only mild or moderate, principally flushing, epigastralgia, and diarrhea. However, DMF exhibited a delayed onset of action, and the dropout rate was high. These aspects highlight the importance of educating patients about the activity profile of DMF, the potential occurrence of side effects, and their management. However, side effects are self-limiting with discontinuation of treatment and generally occur early, allowing patients to be promptly switched to other therapies if DMF is not tolerated. Conclusions: Our results confirm that DMF may be offered as a first-line treatment for moderate psoriasis as it demonstrated efficacy even in the long-term, when treatment is tolerated, especially in patients with a disease duration of less than five years. DMF may also be proposed when the patient presents comorbidities, when immunosuppression is undesired, and/or before the initiation of biolog- ical therapies. ABSTRACT Original Article | Dermatol Pract Concept. 2025;15(4):5458 3 keratinization disorders. However, patient selection must account for lipid metabolism and liver function status [12]. Dimethyl fumarate (DMF) is an FAE with anti- inflammatory and immunomodulating effects, approved by the European Medicines Agency (EMA) for the treatment of patients with moderate-to-severe plaque psoriasis since 2017 [17,18]. Regarding DMF efficacy, the DIMESKIN-2 trial re- ported PASI 75 in 81.1% of patients at week 52 [19], and the BRIDGE Study achieved PASI 75 in 37.5% of patients at week 16 [20]. In a real-world multicenter study, PASI 75 was achieved in 23.3% of patients at week 12, with a fur- ther 17.4% reaching it by week 26. Side effects occurred in 61.1% of patients, with the most common being diarrhea, epigastric discomfort, nausea, and flushing. However, DMF does not display major contraindications [21]. Despite these considerations, DMF is still infrequently prescribed for pso- riasis treatment, and real-life evidence on its use is scarce. We report the results from an Italian multicenter retrospective study on the use of DMF. Objectives The objective of this study was to evaluate the long-term ef- ficacy, safety, and tolerability of DMF in a real-world clinical setting focused on moderate forms of the disease. The study aimed to assess the achievement of disease severity reduction of 50% or 75% (PASI 50 and PASI 75), treatment retention rates, and the occurrence of adverse events over 48 weeks. This work may thus help clarify the role of DMF as first- line systemic therapy, especially for patients with early-stage disease and significant comorbidities. Patients and Methods Study Design This was a retrospective real-world study conducted at the Departments of Dermatology of eight university referral cen- ters in Italy (L’Aquila, Firenze, Roma Tor Vergata, Genova, Roma Cattolica, Roma IFO, Roma Sapienza, Ancona). All subjects enrolled in the study received DMF according to lo- cal guidelines and the summary of product characteristics. Ethical Considerations The investigation was conducted in accordance with the Hel- sinki Declaration and later amendments, and patients signed a consent form authorizing the use of their clinical records for scientific purposes. Confidentiality and privacy of patient data are assured by internal data protection regulations as well as by the General Data Protection Regulation (GDPR) (EU) 2016/679. The study did not require ethical approval in accordance with national guidelines. Patients Patients aged ≥18 years with a diagnosis of moderate psori- asis who underwent DMF treatment for 48 weeks between June 2022 and December 2023, according to standard clini- cal practice, were enrolled in the study. Data Collection Demographic and disease variables, such as age, sex, weight, body mass index (BMI), psoriasis clinical variant, disease du- ration, and PASI, were collected alongside information about previous treatments and the presence of comorbidities. Data collection was carried out while ensuring the anonymity of the participants. Statistycal Analysis The imputation of missing data was performed using the last observation carried forward (LOCF) analysis. A paired Stu- dent t-test was used to compare baseline values with those at each time point (weeks 4, 8, 12, 24, and 48). Data are presented as a percentage of patients who achieved PASI 50 or PASI 75 with a PASI score reduction of 50% and 75% (PASI 50, PASI 75) compared with baseline. To estimate the relationship between variables, a binary logistic regression analysis (binary variables) and a multiple regression analysis (continuous variables) were performed. To account for po- tential confounders, the logistic regression model included the following variables as independent predictors: age, dis- ease duration, BMI ≥ 30, maximum dosage, and number of comorbidities. Statistical analyses were performed using MedCalc® Statistical Software (MedCalc Software Ltd, Os- tend, Belgium; https://www.medcalc.org; 2025). Results A total of 148 patients were enrolled in the study, of whom 94 (63.5%) were male. The mean PASI was 8.9 (±4.2). The average age was 53.8 (range 19–88), and 18 (12.2%) patients had a BMI ≥30 (Table 1). The most prevalent variant of pso- riasis was the plaque type (141 patients, 95.3%), followed by palmoplantar psoriasis (17 patients, 11.5%), inverse psoria- sis (five patients, 3.4%), and psoriatic arthritis (two patients, 1.4%). Most of the population had at least one comorbid- ity (52.7%). Notably, some patients displayed relevant co- morbidities, including various types of anamnestic cancer, hepatitis B virus or hepatitis C virus infections, tuberculosis (TB), or multiple sclerosis. Among the study group, 95 pa- tients (64.2%) had not been previously treated for psoriasis. In contrast, 33.8% had received conventional therapies, including acitretin (16 patients, 10.8%), cyclosporin (31 patients, 20.9%), or MTX (18 patients, 12.2%). A smaller proportion (4.7%) had been treated with biological systemic 4 Original Article | Dermatol Pract Concept. 2025;15(4):5458 Table 1. Patient Baseline Characteristics. Characteristics N=148 Sex (Male) 94 (63.5) Age (years) 53.8 (±16.6, 19–88) Weight (kg) 75.4 (±13.0, 45.0–123.0) BMI (kg/m2) 26.6 (±3.8, 17.6–42.6) BMI ≥30 18 (22.2) Psoriasis clinical variants • Plaque type • Inverse psoriasis • Palmoplantar psoriasis • Psoriatic arthritis 141 (95.3) 5 (3.4) 17 (11.5) 2 (1.4) Disease duration (years) 16.9 (±14.3, 1–65) Mean PASI 8.9 (±4.2) Comorbidities • None • 1 • 2 • 3 • >3 70 (47.3) 31 (20.9) 26 (17.6) 12 (8.1) 10 (6.8) Comorbidities of interest Neoplasms • Malignant melanoma • Non-melanoma skin cancer • Prostate cancer • Colorectal cancer • Thyroid cancer • Parathyroid cancer 9 (6.1%) 3 (2.0%) 2 (1.4%) 1 (0.7%) 1 (0.7%) 1 (0.7%) 1 (0.7%) Infections or other relevant comorbidities • HBV • HCV • IgRA TB positive • Multiple sclerosis 6 (4.1%) 3 (2.0%) 5 (3.4%) 2 (1.4%) Previous therapy None 95 (64.2%) Conventional systemic therapies • Acitretin • Cyclosporin • Methotrexate 50 (33.8%) 16 (10.8%) 31 (20.9%) 18 (12.2%) Biological systemic therapies • TNF inhibitors • Ustekinumab • IL-23 inhibitors 7 (4.7%) 5 (3.4%) 1 (0.7%) 1 (0.7%) Small molecule (apremilast) 7 (4.7%) Data are presented as mean (±SD, range) or N (%). Abbreviations: BMI: body mass index; HBV: hepatitis B virus; HCV: hepatitis C vi- rus; PASI: Psoriasis Area Severity Index; IgRA TB: interferon gamma release assay test for tuberculosis; TNF: tumor necrosis factor. therapies: TNF inhibitors in 3.4% (five patients), usteki- numab in 0.7% (one patient), and IL-23 inhibitors in 0.7% (one patient). Additionally, 4.7% (seven patients) had been treated with apremilast (Table 1). DMF was effective in reducing the mean PASI from baseline at week 4, with efficacy increasing through week 48 (10.0 vs. 1.8, P<0.001, Table 2). The LOCF analysis also showed a significant effect of DMF throughout the obser- vation period, with mean PASI decreasing from 8.9 to 4.3 (P<0.001, Table 2, Figure 1). At 48 weeks, the percentage of pa- tients who achieved PASI 50 was 56.8%, while 36.5% achieved PASI 75 (Table 3, Figure 2). The mean treatment duration was 6.9 (±4.9) months, ranging from 0 to 12 months, reflecting a dropout rate of 62.8%. The main reasons for discontinuing DMF treatment were the appearance of adverse events (61 pa- tients, 41.2%) and inefficacy (28 patients, 18.9%). Most ad- verse events occurred within the first 12 weeks of treatment (39/61, 63.9% versus 22/6, 36.1% after 12 weeks, P<0.001). Interestingly, logistic regression analysis showed that the naïve status of patients as well as prior treatments (expe- rienced) did not influence treatment outcomes with DMF, as observed for the mean PASI and PASI 50 and PASI 75 (Table 4). The analysis also showed that a longer duration of psoriasis was associated with a higher frequency of adverse events upon starting treatment with DMF. DMF treatment was significantly more effective in patients with a disease duration of less than five years after 24 and 48 weeks than in patients with a disease duration of 5–10 or more than 10 years (P=0.04 and P=0.032; Table 5). Furthermore, the treat- ment with DMF was significantly more effective in patients whose disease onset was less than 10 years at 12 (P=0.041), 24 (P=0.011), and 48 weeks (P=0.009) (Table 5, Figure 3). PASI 50 and PASI 75 responses were comparable between bi- ologic/systemic-naïve and previously treated patients at each time point, with no statistically significant difference ob- served (all p-values of t-test >0.1; Table 1). Disease duration, BMI ≥30, maximum dosage, and number of comorbidities did not account for significant differences in achieving PASI 50 or 75 at three months in the logistic regression model. Discussion Conventional systemic treatment of psoriasis relies on the use of MTX, cyclosporin, and acitretin [7]. DMF is an FAE that has been used as a first-line systemic treatment for pso- riasis in recent years because of its good safety profile for long-term therapy [21]. In contrast to cyclosporin, MTX, and acitretin, which are associated with several contrain- dications, potentially severe adverse events, and cumulative organ toxicity [22–24], DMF predominantly causes non- serious and self-limiting side effects [25]. Mechanistically, Original Article | Dermatol Pract Concept. 2025;15(4):5458 5 Figure 1. Mean PASI analyzed using the last observation carried forward analysis (LOCF). The figure shows the decline in PASI over follow-up visits. Table 2. Mean PASI Analysis at Each Visit (as observed) and Mean PASI Analyzed using the Last Observation Carried Forward Analysis (LOCF). PASI analysis Mean (±SD) Paired t-test p-value As observed analysis Baseline vs week 4 N=141, 9.0 (±4.2) N=141, 7.6 (±4.1) <0.001 Baseline vs week 8 N=82, 9.0 (±4.5) N=82, 6.4 (±5.0) <0.001 Baseline vs week 12 N=101, 9.5 (±4.3) N=101, 5.1 (±4.0) <0.001 Baseline vs week 24 N=87, 9.6 (±4.2) N=87, 3.3 (±4.0) <0.001 Baseline vs week 48 N=54, 10.0 (±4.3) N=54, 1.8 (±2.3) <0.001 LOCF analysis Baseline vs week 4 8.9 (±4.2) 7.6 (±4.1) <0.001 Baseline vs week 8 8.9 (±4.2) 6.9 (±4.1) <0.001 Baseline vs week 12 8.9 (±4.2) 5.7 (±4.1) <0.001 Baseline vs week 24 8.9 (±4.2) 4.7 (±4.6) <0.001 Baseline vs week 48 8.9 (±4.2) 4.3 (±4.7) <0.001 Abbreviations: LOCF: last observation carried forward; PASI: Psoriasis Area Severity Index. DMF inhibits NF-kB translocation in fibroblasts and kerat- inocytes, thereby downregulating the production of inflam- matory cytokines and hindering the inflammatory response. Additionally, DMF increases the proportion of regulatory T cells relative to T-helper lymphocytes 17, induces T-cell apoptosis, and inhibits keratinocyte proliferation [18]. Our study showed that DMF is a valid treatment option for patients with moderate psoriasis, as 36.5% of total pa- tients, representing 70.4% of those still on treatment at the timepoint, achieved PASI 75 at week 48. Notably, these re- sults were observed across both treatment-naïve and previ- ously treated individuals, suggesting consistent therapeutic benefit irrespective of prior systemic exposure. Our findings confirmed that DMF is a slow-acting agent that, although starting to reduce PASI by week 4, achieves its full therapeu- tic effect only after several weeks of treatment. The dropout rate was high (62.8%), with the primary reason for discon- tinuation being gastrointestinal issues and flushing. Although these adverse events were mild, they were not tolerated by patients. However, it is important to make a distinction be- tween tolerability and safety. While DMF’s adverse events are frequent and may lead to early discontinuation due to the patient’s low tolerability, they are generally mild, self- limited, and reversible upon treatment cessation. Besides 6 Original Article | Dermatol Pract Concept. 2025;15(4):5458 Table 3. Percentages of Patients Achieving PASI 50 and PASI 75 Analyzed using the Last Observation Carried Forward (LOCF) Analysis. Visit N=148, N (%) PASI 50 4 weeks 9 (6.1%) 8 weeks 14 (9.5%) 12 weeks 46 (31.1%) 24 weeks 75 (50.7%) 48 weeks 84 (56.8%) PASI 75 4 weeks 4 (2.7%) 8 weeks 6 (4.1%) 12 weeks 20 (13.5%) 24 weeks 37 (25.0%) 48 weeks 54 (36.5%) Abbreviations:PASI: Psoriasis Area Severity Index. Figure 2. Percentages of patients achieving PASI 50 and PASI 75 analyzed using the last observation car- ried forward analysis (LOCF). The figure shows the percentages of patients achieving PASI 50 or PASI 75 at different time points during dimethyl fumarate treatment. this, in patients who endured DMF, the drug exerted remark- able and prolonged efficacy in suppressing disease activity, especially in patients with a disease duration of less than five years. Comorbidities, BMI, or dose variations within the studied range did not significantly impact treatment success, underscoring the utility of DMF in diverse patient popula- tions. Furthermore, the analysis showed that the frequency of DMF-induced adverse events was higher in patients with a longer history of psoriasis. This observation supports the postulation that DMF represents a useful first-line therapy option. Moreover, since the adverse events leading to treat- ment discontinuation mainly occurred during the first 12 weeks, patients could be promptly switched to other thera- pies if DMF was not well tolerated. Physicians should inform patients about the frequency and types of adverse events as well as of the possibility of slowly titrating the dosage to minimize them. It is crucial that physicians explain to pa- tients that DMF requires time to exert its clinical effects and that most adverse events are manageable or transient. This proactive approach can help identify patients most likely to tolerate and benefit from long-term DMF therapy [26]. Ad- ditionally, our real-life study revealed that DMF is predomi- nantly prescribed for moderate psoriasis. This pattern of use aligns with DMF’s favorable safety and tolerability profile and with the need for long-term disease control in patients not requiring or not eligible for biologics. Compared to MTX, cyclosporin, and acitretin, DMF of- fers a favorable safety profile. MTX is effective in chronic plaque psoriasis and psoriatic arthritis but requires regular monitoring due to risks of hepatotoxicity and myelosup- pression [2,27,28]. Cyclosporin acts rapidly and is suitable for severe or non-plaque forms but is limited by nephro- toxicity and metabolic effects and is recommended for intermittent use for up to one year [29]. Acitretin is more effective in palmoplantar and hyperkeratotic psoriasis and safe for patients with a history of malignancy due to its non- immunosuppressive profile, but its use is limited by mucocuta- neous side effects, teratogenicity, and potential hepatotoxicity Original Article | Dermatol Pract Concept. 2025;15(4):5458 7 Table 4. Mean PASI and Percentages of Patients Achieving PASI 50 and PASI 75 by Visit and Naïve Status Analyzed using the Last Observation Carried Forward Analysis (LOCF). Visit Mean PASI (Naïve) Mean PASI (Exp) p-value (PASI) PASI 50 (%) Naïve PASI 50 (%) Exp p-value (PASI 50) PASI 75 (%) Naïve PASI 75 (%) Exp p-value (PASI 75) Baseline 8.6 (±3.9) 9.5 (±4.6) 0.190 – – – – – – 4 weeks 7.3 (±3.9) 8.1 (±4.5) 0.228 6.7% (6/89) 5.8% (3/52) 0.820 3.4% (3/89) 1.9% (1/52) 0.619 8 weeks 6.6 (±3.8) 7.4 (±4.5) 0.273 16.3% (8/49) 9.1% (3/33) 0.103 8.2% (4/49) 3.0% (1/33) 0.344 12 weeks 5.4 (±4.0) 6.2 (±4.4) 0.220 41.9% (26/62) 43.6% (17/39) 0.871 22.6% (14/62) 12.8% (5/39) 0.224 24 weeks 4.4 (±4.1) 5.4 (±5.4) 0.209 76.9% (40/52) 77.1% (27/35) 0.981 42.3% (22/52) 34.3% (12/35) 0.455 48 weeks 4.0 (±4.1) 4.7 (±5.6) 0.372 93.9% (31/33) 95.1% (20/21) 0.841 66.7% (22/33) 76.2% (16) – Table 5. Mean Psoriasis Area Severity Index by Visit and Disease Duration Analyzed using the Last Observation Carried Forward Analysis (LOCF). Visit <5 years (N=33) 5–10 years (N=39) >10 years (N=76) p-value (<5/5–10 />10 years) ≤10 years (N=72) >10 years (N=76) p-value (≤10 vs >10 years) Baseline 8.5 (±3.7) 8.7 (±4.6) 9.3 (±4.3) 0.611 8.6 (±4.2) 9.3 (±4.3) 0.336 Week 4 7.0 (±3.5) 7.0 (±4.0) 8.1 (±4.4) 0.314 7.0 (±3.7) 8.1 (±4.4) 0.128 Week 8 6.2 (±3.3) 6.2 (±3.8) 7.5 (±4.5) 0.150 6.2 (±3.6) 7.5 (±4.5) 0.051 Week 12 4.7 (±3.6) 5.2 (±3.8) 6.4 (±4.5) 0.113 5.0 (±3.7) 6.4 (±4.5) 0.041 Week 24 3.6 (±3.7) 3.9 (±3.5) 5.7 (±5.2) 0.040 3.8 (±3.6) 5.7 (±5.2) 0.011 Week 48 3.2 (±3.7) 3.3 (±3.6) 5.3 (±5.4) 0.032 3.3 (±3.6) 5.3 (±5.4) 0.009 [14]. In contrast, DMF lacks cumulative organ toxicity and drug–drug interactions, making it suitable for long-term use, especially in patients with comorbidities or when im- munosuppression is contraindicated or unwanted [30]. Table 6 summarizes the efficacy, safety, and target popula- tions of DMF based on real-world data and compares them with other conventional systemic treatments for psoriasis. The main limitation of this study is its retrospective ob- servational nature, which introduces the potential for se- lection bias, information bias, and confounding variables and does not allow for a direct comparison between DMF treatment and other conventional or biological therapies. Moreover, although the total number of patients enrolled is relatively high, it should be acknowledged that, consider- ing the multicenter design, the sample size could have been larger to enhance the statistical power and generalizability of the findings. Conclusions Our study confirms that, when tolerated, DMF represents a valuable first-line systemic therapeutic option for patients with moderate psoriasis as it can induce long-term disease remission while maintaining a good safety profile. DMF should be offered early in the therapeutic journey as this study shows that it is more efficacious and safer for patients with a disease duration of less than five years. DMF is partic- ularly suitable as first-line therapy in cases where immuno- suppression is undesired or when patients are on multi-drug therapy as it does not exhibit any drug–drug interaction or 8 Original Article | Dermatol Pract Concept. 2025;15(4):5458 Figure 3. Mean PASI by visit and disease duration analyzed using the last observation carried forward analysis (LOCF). Table 6. Comparison between these Real-World Data on Dimethyl Fumarate and Efficacy and Safety of other Conventional Systemic Treatments of Psoriasis. Parameter Dimethyl fumarate [current study] Methotrexate [27,28] Cyclosporin [29] Acitretin [14] Efficacy Moderate efficacy; suitable for long-term management. PASI response lower than methotrexate Moderate efficacy in chronic plaque psoriasis and PsA High short-term efficacy; ideal for rapid disease control in severe psoriasis Moderate efficacy, especially in pustular/ erythrodermic psoriasis; improved with phototherapy Onset of action Gradual; improvement over weeks to months Moderate onset Rapid onset; ideal for acute flares Intermediate onset Tolerability Generally good; adverse events are mostly early, mild, and reversible (GI upset, flushing); most discontinuations occur early Requires regular monitoring due to hepatotoxicity, GI effects, and myelosuppression risks Limited by nephrotoxicity, hypertension, and metabolic issues; requires intermittent short- course use (max ~1 year) Mucocutaneous AEs common (dryness, cheilitis); lipid/ liver changes require monitoring Long-term safety Favorable; lacks cumulative organ toxicity and drug–drug interactions Risk of liver fibrosis and bone marrow suppression with long-term use Not recommended beyond 1 year due to renal/metabolic toxicity risks Teratogenicity (up to 3 years post-therapy), hepatotoxicity, and hyperlipidemia may limit use Immunosuppressive activity No Yes Yes No Best-suited patients Patients with comorbidities, contraindications to immunosuppressants, or requiring long-term treatment Patients with extensive plaque psoriasis or joint involvement and no hepatic or hematological contraindications Patients with rapidly progressive, severe disease requiring fast symptom control Male or postmenopausal patients with keratinization disorders or pustular/ erythrodermic psoriasis; not for women of childbearing potential Abbreviations: AE: adverse event; GI: gastrointestinal; PASI: Psoriasis Area Severity Index; PsA: psoriatic arthritis. 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