Summary
Background
Tildrakizumab is a specific anti‐interleukin‐23p19 monoclonal antibody approved for the treatment of plaque psoriasis.
Objectives
To evaluate the long‐term efficacy and safety of ...tildrakizumab treatment for patients with moderate‐to‐severe psoriasis for up to 148 weeks.
Methods
Pooled analysis from two double‐blind, randomized controlled trials: reSURFACE 1 and reSURFACE 2. Efficacy was assessed for responders (≥ 75% improvement in Psoriasis Area and Severity Index; PASI 75) and partial responders (PASI 50–75) to tildrakizumab 100 mg and 200 mg at week 28 who were maintained on the same dose (administered every 12 weeks), and for partial responders or nonresponders (PASI < 50) to etanercept 50 mg at week 28 who, after a 4‐week washout, were switched to tildrakizumab 200 mg (administered at weeks 32 and 36, and every 12 weeks thereafter). Safety was assessed in the all‐patients‐as‐treated population. Three different methods of imputing missing data were used: nonresponder imputation (NRI), multiple imputation and observed cases. The Clinicaltrials.gov numbers are NCT01722331 (reSURFACE 1) and NCT01729754 (reSURFACE 2).
Results
At week 148 (NRI), 72·6%, 53·8% and 28·9% of tildrakizumab 100‐mg responders and 80·2%, 59·9% and 32·6% of tildrakizumab 200‐mg responders had PASI 75, 90 and 100 responses, respectively. For partial responders to tildrakizumab 100 mg and 200 mg, the proportions of patients achieving PASI 75, 90 and 100 responses were 32·5%, 25·0% and 10·0%; and 47·1%, 27·5% and 12·8%, respectively. For patients who were partial responders or nonresponders to etanercept, the proportions of patients achieving PASI 75, 90 and 100 responses were 66·9%, 43·8% and 14·9% at week 148. Rates of discontinuations due to adverse events tildrakizumab 100 mg: 1·7 per 100 patient‐years (PYs); tildrakizumab 200 mg: 1·2 per 100 PYs and exposure‐adjusted rates of serious adverse events (5·9 per 100 PYs; 5·5 per 100 PYs), severe infections (1·1 per 100 PYs; 1·1 per 100 PYs), malignancies (0·6 per 100 PYs; 0·4 per 100 PYs) and major adverse cardiovascular events (0·4 per 100 PYs; 0·5 per 100 PYs) were low.
Conclusions
Tildrakizumab was well tolerated and efficacy was well maintained in week 28 responders who continued tildrakizumab treatment through 3 years, or improved among etanercept partial responders or nonresponders who switched to tildrakizumab.
What's already known about this topic?
Tildrakizumab 100 mg and 200 mg are efficacious and well tolerated with short‐term use in the treatment of patients with moderate‐to‐severe plaque psoriasis.
What does this study add?
High levels of efficacy are maintained for up to 3 years of psoriasis treatment with tildrakizumab.
There is a favourable long‐term safety profile with both tildrakizumab 100 mg and 200 mg, with a low incidence of adverse events of special interest through 3 years.
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Summary
Background
The phase III reSURFACE 1 and reSURFACE 2 (NCT01722331/NCT01729754) trials of the anti‐interleukin‐23p19 monoclonal antibody tildrakizumab (TIL) for psoriasis treatment are ...complete.
Objectives
We present 5‐year pooled data from reSURFACE 1 and reSURFACE 2.
Methods
reSURFACE 1 and reSURFACE 2 were double‐blind, randomized, controlled studies with optional long‐term extensions. Adults with moderate‐to‐severe chronic plaque psoriasis were randomized 2 : 2 : 1 to TIL 100 mg (TIL 100) or 200 mg (TIL 200) or placebo at weeks 0 and 4, and every 12 weeks thereafter reSURFACE 2 included an etanercept (ETN) arm. Efficacy outcomes included proportions of patients achieving absolute and relative improvement from baseline Psoriasis Area and Severity Index (PASI) score through week 244 in TIL responders (≥ 75% improvement from baseline PASI; PASI 75 response) continuously receiving the same dose and ETN partial responders and nonresponders (PASI < 75 response) switched to TIL 200 at week 28. Safety was assessed from adverse events (AEs) in all patients as treated.
Results
Efficacy analyses included 329 and 227 week 28 responders to TIL 100 and TIL 200, respectively, and 121 ETN partial responders/nonresponders switched to TIL 200 at week 28. Of TIL 100 or TIL 200 responders and ETN partial responders/nonresponders entering the extensions, 235/302, 176/213 and 85/107, respectively, were evaluated at week 244, and 88·7%, 92·5% and 81·3%, respectively, achieved PASI 75 response. Exposure‐adjusted rates of serious AEs were 6·3 and 6·0 patients with events per 100 patient‐years of TIL 100 and TIL 200, respectively.
Conclusions
TIL treatment provided sustained disease control over 5 years in week 28 TIL responders and ETN partial responders/nonresponders, with a reassuring safety profile.
What’s already known about this topic?
Tildrakizumab (TIL) is approved for treatment of moderate‐to‐severe psoriasis, and 3‐year data have been previously published.
Long‐term efficacy and safety data of biological therapies is crucial to inform clinical practice.
What does this study add?
TIL is the first anti‐interleukin‐23p19 treatment for which 5‐year efficacy and safety data are reported from two phase III studies, reSURFACE 1 and reSURFACE 2.
These data provide evidence of sustained efficacy in TIL responders and in patients switched from etanercept to TIL at week 28, and a favourable long‐term safety profile with total TIL exposure of over 5400 patient‐years.
Linked Comment: C.G. Purvis et al. Br J Dermatol 2021; 185:242–243.
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Summary
Background
Fumaric acid esters (FAEs) are recommended in international guidelines for induction and long‐term treatment of adults with moderate‐to‐severe chronic plaque psoriasis. The fixed ...combination Fumaderm® is approved in Germany, with dimethyl fumarate (DMF) being the main active ingredient.
Objectives
To assess the efficacy and safety of a new formulation of DMF (LAS41008), compared with placebo and Fumaderm®, in adults with moderate‐to‐severe chronic plaque psoriasis.
Methods
In this phase III, double‐blind, placebo‐controlled, noninferiority trial (BRIDGE, NCT01726933, EudraCT 2012‐000055‐13), patients were randomized to receive LAS41008, Fumaderm® or placebo (2 : 2 : 1) for 16 weeks, uptitrating to a maximum daily DMF dose of 720 mg, depending upon individual response. The coprimary end points were the percentage of patients achieving ≥ 75% improvement in Psoriasis Area and Severity Index (PASI 75) and the percentage achieving a score of ‘clear’ or ‘almost clear’ in the Physician's Global Assessment (PGA) at week 16.
Results
In total, 671 patients were randomized and included in the full analysis set (n = 267, LAS41008; n = 273, Fumaderm®; n = 131, placebo). At week 16, 37·5% of patients treated with LAS41008 achieved PASI 75, compared with 15·3% receiving placebo (superiority for LAS41008 vs. placebo: P < 0·001) and 40·3% receiving Fumaderm® (noninferiority for LAS41008 vs. Fumaderm®: P < 0·001). Overall, 33% of patients treated with LAS41008 were ‘clear’ or ‘almost clear’ in the PGA at week 16, compared with 13·0% receiving placebo (P < 0·0001; LAS41008 superiority vs. placebo) and 37·4% receiving Fumaderm®. Most treatment‐related adverse events were classed as ‘mild’ in severity.
Conclusions
LAS41008 (DMF) is effective in the treatment of adults with moderate‐to‐severe chronic plaque psoriasis.
What's already known about this topic?
A combination of fumaric acid esters (FAEs), including dimethyl fumarate (DMF), is approved for the treatment of moderate‐to‐severe psoriasis in Germany, with a positive risk–benefit profile for long‐term use.
Despite being recommended in international treatment guidelines, FAEs are not available in most European countries.
What does this study add?
This international, randomized, double‐blind trial demonstrates the efficacy and safety of LAS41008 (DMF) for the treatment of adults with moderate‐to‐severe chronic plaque psoriasis.
Linked Comment: Balak. Br J Dermatol 2017; 176:563–564.
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Background
Limited data are available on long‐term efficacy and safety of biologics in patients with psoriasis and metabolic syndrome (MetS), a common comorbidity.
Objectives
This analysis updates ...tildrakizumab efficacy and safety for up to 5 years in patients with and without MetS.
Methods
This was a post hoc analysis of the double‐blind, randomized, placebo‐controlled, phase 3 reSURFACE 1 (NCT01722331) and reSURFACE 2 (NCT01729754) trials in adult patients with moderate to severe chronic plaque psoriasis. Analyses included data through Week 244 from patients who continuously received tildrakizumab 100 (TIL100) or 200 mg (TIL200) and entered the extension studies, stratified by baseline MetS status. Efficacy was assessed via Psoriasis Area and Severity Index (PASI) scores. Safety was evaluated from exposure‐adjusted incidence rates (EAIRs) of treatment‐emergent adverse events (TEAEs).
Results
reSURFACE 1 and reSURFACE 2 analyses included 26 and 44 TIL100‐treated patients with MetS, 98 and 167 TIL100‐treated patients without MetS, 34 and 30 TIL200‐treated patients with MetS, and 111 and 130 TIL200‐treated patients without MetS, respectively. There were no clinically relevant differences in PASI 75/90/100 response rates at Week 244 between patients with vs without MetS. The proportion of patients with vs without MetS achieving absolute PASI score <3 at Week 244 was 53.8% vs 69.4% and 77.3% vs 80.8% in reSURFACE 1 and 2, respectively, for TIL100‐treated patients and 58.8% vs 72.1% and 63.3% vs 72.3%, respectively, for TIL200‐treated patients. In both studies, median reduction from baseline PASI score at all time points in patients with vs without MetS was >83% vs >89% for TIL100 and >85% vs >90% for TIL200. Pooled EAIRs of TEAEs, serious TEAEs, and TEAEs of special interest were similar in patients with and without MetS.
Conclusions
Tildrakizumab maintains efficacy and a favorable safety profile over 5 years in patients with psoriasis regardless of MetS status.
Background
Psoriasis is a chronic inflammatory skin disease associated with quality of life (QoL) impairment. BRIDGE was a randomized, double‐blind, phase III study comparing the efficacy and safety ...of dimethylfumarate (DMF) with a fixed combination of fumaric acid esters (FAE) or placebo for the treatment of moderate‐to‐severe psoriasis.
Objectives
This post hoc analysis investigated treatment effect on QoL overall and by patient subgroups categorized by disease severity. Week 8 efficacy responses were also investigated as possible predictors of Week 16 Dermatology Life Quality Index (DLQI) outcomes.
Methods
Patients were randomized to receive a maximum daily dose of 720 mg of DMF, FAE (gradual up‐titration) or placebo for 16 weeks. Psoriasis Area Severity Index, Body Surface Area, Physician's Global Assessment and DLQI were assessed at baseline, Weeks 8 and 16. DLQI 0‐1 indicated ‘no effect on patient life’. Associations between baseline severity, Week 16 DLQI and Week 8 efficacy (as observed cases) were also examined.
Results
At baseline, 671 patients were included in the full analysis set (267 randomized to DMF, 273 to FAE and 131 to placebo). DMF was superior to placebo (P < 0.001) and not significantly different to FAE regarding Week 16 DLQI outcomes (P > 0.05). Baseline disease severity did not impact DLQI outcomes at Week 16. In DMF‐ and FAE‐treated patients, Week 8 PASI 50/75 responders reported better DLQI responses at Week 16 vs non‐responders (P < 0.05). Week 8 PASI ≤ 3 and/or PGA 0‐1 responders were also more likely to report DLQI 0‐1 at Week 16 vs non‐responders (P < 0.05).
Conclusion
Dimethylfumarate significantly improved DLQI outcomes vs. placebo and was not affected by baseline disease severity. Efficacy responses (PASI 50/75, PASI ≤3 and PGA 0‐1) as early as Week 8 were predictive of QoL outcomes at Week 16 in DMF‐ and FAE‐treated patients.
Background
Anti‐MDA5 (Melanoma differentiation‐associated gene 5) positive dermatomyositis is a new variant of clinically amyopathic dermatomyositis that presents with characteristic mucocutaneous ...findings and is associated with a higher risk of developing rapidly progressive interstitial lung disease. Because its presentation differs from that of classical dermatomyositis, this entity can be a diagnostic challenge for the clinician.
Methods & Results
We present the case of a 55‐year‐old male with a 7‐month history of chill sensation, constitutional symptoms and polyarthralgia. Within 3 months, the patient developed progressive heart failure with dyspnoea and orthopnoea, together with characteristic cutaneous lesions. Skin biopsies demonstrated thrombosis of small and medium‐sized arteries in the reticular dermis, together with an evolved lobular panniculitis and prominent mucin deposits.
Conclusions
Clinicians should be aware of the characteristic clinical and histopathologic presentation of this variant of dermatomyositis to establish an early diagnosis. Further evidence is needed to clarify the risk of cardiac involvement in this subset of patients.
Summary
Psoriasis is a common skin condition that causes red and scaly patches of skin. About 2% of people worldwide suffer from psoriasis. The authors of this study wanted to see how well the drug ...tildrakizumab treats psoriasis and the side effects it may have with long‐term use.
In order to do so, they combined information from two clinical trials called reSURFACE 1 and reSURFACE 2. The authors examined the improvement of psoriasis symptoms using a scoring method named PASI (Psoriasis Area Severity Index) for a period of three years. This method grades the severity of a person's psoriasis and helps to measure any improvement.
In clinical trials, success is measured by the proportion of patients who achieve a “PASI 75” or “PASI 90”, which means a 75% or 90% reduction of the PASI score from the beginning of the treatment. Additionally, an excellent response to treatment can also be described by reaching a low PASI score such as a PASI score of less than 3 or less than 1 point.
The authors found a high proportion of patients achieving an improvement in PASI during the first year that was well maintained with continued tildrakizumab 100 or 200 mg and, after three years, 80% and 60% of patients, respectively, achieved a PASI 75 and a PASI 90.
Looking at PASI scores, 70% and 50% of patients, respectively, maintained a PASI score of less than 3 and less than 1, after three years. Even the patients who initially had a poor response (i.e. not much improvement) to tildrakizumab showed an improvement over time, if the treatment was maintained. Patients previously treated with etanercept (another drug for psoriasis) unsuccessfully, saw an improvement of their psoriasis with only two doses of tildrakizumab, with 80% and 40% of patients, respectively, achieving a PASI 75 and a PASI 90.
Very few undesirable effects were seen, and no new or unexpected side effects were reported. The most frequent side effect was nasopharyngitis, which is commonly known as a cold. Severe infections, malignancies, or cardiovascular effects were uncommon and comparable to placebo (an inactive substance, like a “sugar pill”), indicating no increased risk of these events with tildrakizumab.
In conclusion, tildrakizumab proved to be a good treatment for psoriasis for as long as three years, which is safe and has very few side effects.
This is a summary of the study: Long‐term efficacy and safety of tildrakizumab for moderate‐to‐severe psoriasis: pooled analyses of two randomized phase III clinical trials (reSURFACE 1 and reSURFACE 2) through 148 weeks
Linked Article: Reich et al. Br J Dermatol 2020; 182:605–617
Child abuse is far more prevalent today than is generally recognized. Up to 90% of victims suffer physical abuse that can be observed in signs on the skin. Dermatologists are particularly qualified ...to identify these signs and distinguish them from other conditions that can mimic abuse. This review covers the signs of child abuse that can be observed on the skin. We discuss clues that can help differentiate between lesions caused by abuse and those that are accidental, and we describe the skin conditions that mimic physical abuse.
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