- I derivati dell’acido fumarico (FAD), incluso il dimetil fumarato (DMF), sono approvati per il trattamento sistemico della psoriasi moderata-severa dell’adulto.
- Il presente studio ha mostrato che il profilo d’efficacia e la sicurezza del DMF per l’uso a lungo termine è simile a quanto descritto in precedenza per i fumarati e comparabile ad altri agenti sistemici. Il DMF può rappresentare la scelta da preferire nei pazienti con pregressi fallimenti terapeutici multipli con effetti collaterali emergenti, grazie al suo favorevole profilo di sicurezza a lungo termine.
Fumaric acid derivatives (FADs), including dimethyl fumarate (DMF), are approved systemic treatment for moderate-to-severe plaque psoriasis in adult patients. Most studies on the efficacy and safety of FADs are meta-analyses of randomized clinical trials and observational studies. To provide a real-life assessment of the long-term efficacy and safety of DMF compared with other systemic treatments, we prospectively followed a cohort of patients with psoriasis in the North-Eastern Italy between January 2011 and September 2021, analysing data of the PsoReal registry. The study was approved by the Ethics Committees of the participating centres. Each patient included had signed an informed consent form.
Overall, 208 adult patients with psoriasis, 70 who were prescribed DMF (mean age 53.4 ± 15.1 years, males 71.4%), and 138 who received other systemic treatments for psoriasis (mean age 52.0 ± 14.7 years, males 71.0%), including cyclosporin, methotrexate, acitretin and apremilast, referring to the same centres during the same period, were included.
At baseline, the two groups did not significantly differ except for the presence, in patients on DMF compared with those under other systemic treatments, of a lower body mass index (26.0 vs. 27.9, p = 0.004), a lower prevalence of psoriatic arthritis (8.6% vs 23.1%, p <0.001), and of main comorbidities, including diabetes, hypertension, hyperlipemia or neoplasm (38.6% vs. 59.4%, p = 0.004). Patients on DMF had used systemic therapies for psoriasis, including biologics, more frequently than patients under other systemic treatments (73.4% vs. 50.7%, p = 0.003).
The mean follow-up was 25.9 ± 15.6 months. During the first 36 months, a significant switch to other conventional or biological therapies was observed in both groups (P <0.001). At month 36, both groups achieved a significant improvement in the mean Psoriasis Area and Severity Index (PASI) score from baseline (p <0.001). This improvement started earlier in the group receiving other systemic treatments compared with the DMF group, i.e. at third and at sixth month, respectively. When comparing patients on DMF versus patients under other systemic treatments through cumulative PASI75 up to the first therapy discontinuation, we found, from month 9 onwards, a slightly superior improvement in the DMF group, although without any statistically significant difference. The median time to achieve 50% response rate for cumulative PASI75 in the group receiving DMF was 19.8 (95% CI: 12.5-27) months, which was comparable or even lower than the results of previous studies. At 12 months about one third of patients achieved PASI75. Even when focussing the analysis on the efficacy of each conventional treatment versus DMF, the different treatments were comparable.
In line with the literature, the main reason for treatment discontinuation or switching was the occurrence of side-effects (42.9%), mostly gastrointestinal, including diarrhoea, abdominal distension or pain, nausea and vomiting, in patients on DMF, and the lack of efficacy (51.4%) in patients under other systemic treatments. The median time to reach the first side-effect up to treatment discontinuation was 18.9 months (95% CI: 4.1-33.7) in patients on DMF, and 16.5 months (95% CI: 12.4-20.5) in patients under other systemic treatments. In both groups cumulative incidence of side-effects peaked up around month 6, then it maintained slightly lower in the DMF group, although without any significant difference compared with the group of other systemic treatments.
Limitations of our study include the patients’ small sample size, the patients’ loss to follow-up, the presence of missing data and the different observational periods.
We conclude that the efficacy and the safety profile of DMF for long-term clinical use are similar to those previously described with fumarates and comparable with other systemic agents. DMF may be the preferred choice for multi-failure psoriasis patients with treatment-emergent side-effects, due to its favourable long-term safety profile.