Bimekizumab efficacy and safety in patients with moderate to severe plaque psoriasis: Two-year interim results from the open-label extension of the randomized BE RADIANT phase 3b trial.

BACKGROUND: Bimekizumab is a monoclonal IgG1 antibody that inhibits interleukin-17A/F. Bimekizumab is more efficacious than secukinumab over 1 year in the treatment of psoriasis. OBJECTIVE: Evaluate the safety and efficacy of bimekizumab through 2 years in patients with moderate to severe plaque psoriasis. METHODS: The BE RADIANT phase 3b randomized controlled trial consisted of a 48-week double-blinded period, where patients received bimekizumab (320 mg every 4 or 8 weeks) or secukinumab (300 mg weekly to Week 4, then every 4 weeks), and an open-label extension (OLE). From Week 48, all patients received bimekizumab in the OLE. RESULTS: At Week 48, more patients achieved complete skin clearance (PASI 100; modified non-responder imputation) with bimekizumab than secukinumab (74.8% vs 52.8%). PASI 100 responses were maintained to Week 96 in continuous bimekizumab patients (70.8%); patients who switched from secukinumab to bimekizumab had increased rates at Week 96 (76.6%). The most common adverse events were: nasopharyngitis, oral candidiasis, and urinary tract infection. Safety data were consistent with the known safety profile of bimekizumab. LIMITATIONS: Limited racial diversity; overlap with the COVID-19 pandemic. CONCLUSIONS: High PASI 100 responses achieved with bimekizumab over 48 weeks were sustained through Week 96; secukinumab patients who switched to bimekizumab achieved similar responses by Week 96.

Efficacy of Bimekizumab and Other Biologics in Moderate to Severe Plaque Psoriasis: A Systematic Literature Review and a Network Meta-Analysis.

INTRODUCTION: Biologic treatments are increasingly being used in the management of moderate to severe plaque psoriasis (PSO). Bimekizumab is a selective inhibitor of both interleukin (IL)-17A and IL-17F approved for the treatment of moderate to severe PSO. Although bimekizumab trials provide comparisons to secukinumab, adalimumab and ustekinumab, there are no further head-to-head comparisons of bimekizumab to other biologics. This network meta-analysis (NMA) aimed to compare the short-term efficacy of bimekizumab versus other biologic systemic therapies for moderate to severe PSO. METHODS: A systematic literature review was conducted to identify randomised controlled trials (RCTs) in patients with moderate to severe PSO. MEDLINE, Embase, the Cochrane Central Register of Controlled Trials and the Database of Systematic Reviews and PsycINFO were searched on July 1, 2020. An enhanced multinomial Bayesian NMA model was used to evaluate the comparative efficacy in 50%, 75%, 90% and 100% improvement from baseline Psoriasis Area and Severity Index (PASI 50/75/90/100) at 10-16 weeks. The model was also adjusted for baseline risk, given the variable placebo responses across the trials. RESULTS: Eighty-six RCTs (including 34,476 patients) were included in the NMA. IL-17 and IL-23 inhibitors were the most effective treatments across all PASI levels. At 10-16 weeks, bimekizumab had the highest probability of achieving PASI 75 (92.3%), PASI 90 (84.0%) and PASI 100 (57.8%). Bimekizumab demonstrated statistical superiority over all biologics in achieving PASI 90 and PASI 100 thresholds. For PASI 75, the benefit of bimekizumab was statistically significant compared to all other treatments except risankizumab and ixekizumab. CONCLUSION: This analysis demonstrated that IL-17 and IL-23 inhibitors were highly effective in achieving short-term improvement among patients with moderate to severe PSO. Patients receiving bimekizumab were significantly more likely to achieve PASI 90 or PASI 100 within 10-16 weeks of the first injection than all other biologics.

Quality-of-Life Outcomes, Effectiveness and Tolerability of Apremilast in Patients with Plaque Psoriasis and Routine German Dermatology Care: Results from LAPIS-PSO.

INTRODUCTION: Psoriasis is a systemic inflammatory disease characterised by pruritic skin lesions that impair quality of life (QOL). Long-Term Documentation of the Utilization of Apremilast in Patients with Plaque Psoriasis under Routine Conditions (LAPIS-PSO; ClinicalTrials.gov: NCT02626793) was a 52-week, prospective, multicentre, observational cohort study conducted in real-world dermatology clinical settings in Germany. We evaluated physician- and patient-reported outcomes for QOL, effectiveness and tolerability in patients with moderate to severe psoriasis vulgaris in LAPIS-PSO. METHODS: The primary endpoint was the percentage of patients achieving Dermatology Life Quality Index (DLQI) score ≤ 5 or ≥ 5-point improvement from baseline in DLQI score at visit 2 (~ 4 months after baseline). Secondary endpoints included assessments of symptoms and disease severity. Tolerability was evaluated based on adverse events (AEs). A pre-defined subgroup analysis based on baseline Physician's Global Assessment (PGA) score (2 or 3 versus 4) was performed. Data were examined descriptively through visit 5 (~ 13 months) using the last-observation-carried-forward (LOCF) approach and data as observed. RESULTS: In total, 257 patients were included for efficacy assessment. On LOCF analysis, most patients achieved the primary endpoint at visit 2 (66.5%); DLQI response was maintained at visit 5 (72.4%). Earlier treatment response was observed in patients with a PGA score of 2 or 3 versus 4 (visit 1 PASI ≤ 3: 20.5% versus 10.8%). Adverse events were consistent with the known safety profile of apremilast. CONCLUSIONS: In routine clinical care in Germany, patients with moderate to severe plaque psoriasis benefited from apremilast treatment up to ~ 13 months, consistent with findings from clinical trials, with a good safety profile.

Efficacy and safety of fumaric acid esters in combination with phototherapy in patients with moderate-to-severe plaque psoriasis (FAST).

BACKGROUND: While treatment of patients with moderate-to-severe psoriasis using a combination of fumaric acid esters (FAE, Fumaderm® ) and phototherapy (UV) is common practice, there have been hardly any studies investigating this regimen. Available information is limited to data from a small pilot study. The objective of the present study was to evaluate FAE/UV combination therapy in a larger patient cohort with moderate-to-severe psoriasis. PATIENTS AND METHODS: In this prospective noninterventional multicenter study, data from patients treated with FAE/UV combination therapy was assessed with regard to efficacy (PGA' PASI, DLQI, EQ-5D), safety, and dosage over a twelve-month period. The findings were subsequently compared to data from a previous retrospective study on FAE monotherapy. RESULTS: Data from 363 patients was included in the analysis. Efficacy measures improved substantially on combination therapy. Compared to FAE monotherapy, FAE/UV therapy led to a faster clinical response, however, there was no difference in efficacy after 12 months. Neither the duration nor the type of phototherapy had an impact on efficacy. In general, combination therapy was well tolerated. Seven percent of patients experienced adverse events. CONCLUSIONS: FAE/UV combination therapy is effective and well tolerated in patients with moderate-to-severe psoriasis. Such treatment may induce a faster therapeutic response, and appears to be useful, particularly in the first three months of FAE therapy.

Wirksamkeit und Sicherheit von Fumarsäureestern in Kombination mit Phototherapie bei Patienten mit moderater bis schwerer Plaque-Psoriasis (FAST).

HINTERGRUND: Die Behandlung von Psoriasis-Patienten mit einer Kombination aus Fumarsäureestern (FSE, Fumaderm® ) und Phototherapie (UV) ist verbreitet, wurde aber im Rahmen von Studien wenig untersucht. Bisher liegen lediglich Daten aus einer kleinen Pilotstudie vor. Intention dieser Studie war, eine FSE/UV-Kombinationsbehandlung an einem größeren Patientenkollektiv mit mittelschwerer bis schwerer Psoriasis zu untersuchen. PATIENTEN UND METHODIK: In dieser prospektiven, multizentrischen, nichtinterventionellen Studie wurden Daten von Patienten mit FSE/UV-Kombinationstherapie hinsichtlich der Wirksamkeit (PGA' PASI, DLQI, EQ-5D), Sicherheit und Dosierung über einen Zeitraum von zwölf Monaten erfasst und mit Daten einer retrospektiven Studie mit FSE-Monotherapie verglichen. ERGEBNISSE: Es wurden Daten von 363 Patienten ausgewertet. Unter der Kombinationstherapie verbesserten sich alle Wirksamkeitsparameter deutlich. Im Vergleich zur Monotherapie mit FSE konnte durch die Kombination mit UV ein schnellerer Wirkeintritt erzielt werden, wobei nach zwölf Monaten kein Unterschied in der Wirksamkeit bestand. Die Dauer und Art der Phototherapie zeigte keinen Einfluss auf die Wirksamkeitsparameter. Allgemein wurde die Kombinationstherapie gut vertragen. Unerwünschte Ereignisse wurden bei 7 % der Patienten berichtet. SCHLUSSFOLGERUNGEN: Die FSE/UV Kombinationstherapie zeigt eine gute Wirksamkeit und Verträglichkeit und kann zu einem schnelleren Wirkeintritt führen. Eine Kombinationstherapie erscheint vor allem in den ersten drei Monaten der FSE Behandlung sinnvoll.