Sequential treatment with biologics: switching from efalizumab to etanercept in 35 patients with high‐need psoriasis

Background Use of biological agents has been shown to be an efficacious approach in psoriasis, when traditional treatments fail. However, there are limited data on the effectiveness and safety of switching from one biological agent to another. Objectives We aimed to evaluate the effectiveness and safety of etanercept as a sequential treatment in patients previously treated with efalizumab, and to evaluate different transition strategies from efalizumab to etanercept. Methods We present a retrospective study in patients with high‐need plaque psoriasis who were unable to continue efalizumab and were immediately switched to etanercept. Results We included 35 patients during a 4.5‐year period. At 24 weeks of etanercept therapy, 57% of patients had a PASI reduction of 75%, suggesting that alternating between biological agents is feasible. We used three different switching approaches: (i) etanercept in combination with cyclosporine as bridge therapy, (ii) etanercept in combination with methotrexate as bridge therapy, (iii) etanercept monotherapy. Combination therapy was efficacious in all patients, including eight patients with rebound phenomenon with efalizumab. Etanercept was discontinued in two patients as a result of serious adverse events that consisted of an oral squamous cell carcinoma and a diffuse B‐cell‐non‐Hodgkin lymphoma. Conclusions In our experience, it seems that etanercept alone may not be sufficient when transitioning from efalizumab in high‐need patients with severe worsening or rebound of psoriasis. In such patients, combination of etanercept with cyclosporine or methotrexate is a more effective approach. Non‐response to efalizumab did not preclude clinical response after switching to etanercept.     

Switch from etanercept to efalizumab in a psoriatic patient with HCV infection: a case report

Psoriasis vulgaris is a chronic dermatosis and is a widespread dematological disease. The most represented lesions are erythemato-squamous plaques with a tendency to cover large body areas with a great impairment of normal activities and a poor quality of life. Very often psoriasis is associated to other illnesses and the dermatologist has to be aware that comorbidities have to be taken in account for a successfull treatment of the disease.
We report a case of a patient affected by severe psoriasis and HCV infection. He underwent a first treatment with etenarcept with good clinical results and no change of his viral load. When etenarcept became ineffective, he received efalizumab, with a good control of his dermatological condition and a reduction of the viral load.     

Patients with moderate-to-severe psoriasis recapture clinical response during re-treatment with etanercept

Background  Patients with psoriasis experience remission and gradual reappearance of erythematous and scaly plaques and require individualized treatment over time. A goal of psoriasis treatment is to provide optimal efficacy with a flexible therapeutic regimen that may include treatment pauses.
Objectives  To determine whether patients receiving initial treatment with etanercept who then pause therapy would subsequently recapture response during re-treatment.
Patients and methods  A post-hoc analysis of 226 patients with moderate-to-severe psoriasis from a large multicentre trial was performed. Patients had received etanercept 50 mg twice weekly subcutaneously until a target clinical response had been achieved, then had paused treatment and eventually relapsed. They were then re-treated with etanercept 25 mg twice weekly. The number of patients recapturing a Physician Global Assessment (PGA) of psoriasis rating of ≤ 2 (clear, almost clear or mild) on first re-treatment was assessed. Patient satisfaction during the initial treatment and first re-treatment period was also determined.
Results  A total of 187 (83%) patients recaptured the target clinical response of a PGA of ≤ 2 after re-treatment. The majority of patients [219 of 226 (97%)] reported satisfaction with etanercept re-treatment. No new safety concerns emerged during re-treatment.
Conclusions  In this post-hoc analysis, patients with psoriasis who were re-treated with etanercept 25 mg twice weekly effectively recaptured clinical responses that patients found satisfactory. A flexible treatment option is available to dermatologists and patients for individualized care.     

Switching from etanercept to adalimumab is effective and safe: results in 30 patients with psoriasis with primary failure,secondary failure or intolerance to etanercept

Background Knowledge on the sequential treatment of psoriasis with biologics with regard to efficacy and safety is sparse. This also applies to the efficacy and safety of adalimumab in patients previously treated with etanercept. The relationship between the reasons for discontinuation of etanercept and the response to adalimumab is not clear in psoriasis. Objectives To evaluate the efficacy and safety of adalimumab in patients with psoriasis with primary failure, secondary failure or intolerance to etanercept in daily practice. Methods Data were extracted from two prospective registries from all patients with psoriasis with failure on etanercept treatment, who switched to adalimumab therapy. Thirty patients fulfilled these criteria. All patients were naive to biologics when etanercept was initiated. Primary endpoints were the percentage of patients achieving a 50% or 75% improvement of the baseline Psoriasis Area and Severity Index (PASI) score (PASI 50 and PASI 75, respectively) at weeks 12, 24 and 48. Secondary endpoints were the percentage of patients achieving PASI 90, the mean percentage improvement in the PASI score from baseline and the adverse event rate. Results Compared with the baseline PASI score before the start of etanercept, the mean percentage improvement in PASI and the PASI 50/75/90 response rates to adalimumab until week 48 were comparable to those achieved with etanercept. In the patients failing on etanercept, PASI 75 was achieved by 27%, 36% and 54% at weeks 12, 24 and 48 of adalimumab treatment, respectively. The majority of patients showed a beneficial response to adalimumab, irrespective of the reason for discontinuation of etanercept. Previous treatment with etanercept did not increase the adverse event rate nor change the nature of the side‐effects. Conclusions Adalimumab seems to be an effective and safe treatment option for patients with psoriasis who failed on etanercept treatment irrespective of the reason for discontinuation.     

Comparison of clinical and pharmacokinetic profiles of etanercept 25 mg twice weekly and 50 mg once weekly in patients with psoriasis

BACKGROUND: Etanercept is a tumour necrosis factor antagonist that is approved in the U.S.A., Canada and Europe for treating adult patients with chronic moderate to severe plaque psoriasis. OBJECTIVES: To assess whether clinical efficacy, safety and pharmacokinetic (PK) profiles of etanercept 50 mg once weekly are comparable to etanercept 25 mg twice weekly. METHODS: Patients from a U.S. phase 3 study and a global phase 3 study were subsequently enrolled in an open-label extension study (extension study) where they all received etanercept at a dose of 50 mg once weekly for an initial 12 weeks. Patients who had received at least 24 weeks of etanercept 25 mg twice weekly in the global phase 3 study and were enrolled in the extension study (n = 265) were assessed for efficacy and safety at extension study baseline and after 12 weeks of etanercept 50 mg once weekly. Efficacy endpoints included the Psoriasis Area and Severity Index (PASI), the Dermatology Life Quality Index and the Physician's Global Assessment of psoriasis. In addition, PK profiles from patients in the U.S. phase 3 study were compared with PK profiles from another set of patients in the extension study. Comparison was made between a subset of patients receiving etanercept 25 mg twice weekly dosing in the U.S. phase 3 study (n = 13) and those receiving etanercept 50 mg once weekly in the extension study (n = 84). RESULTS: The mean PASI score was 5.77 at extension study baseline after treatment with etanercept 25 mg twice weekly, which was sustained at 5.82 after 12 weeks of etanercept 50 mg once weekly. Similar results were observed in other efficacy endpoints. Etanercept 50 mg once weekly was generally well tolerated. No new safety findings were reported. PK profiles overlapped extensively between the two dosing regimens. CONCLUSIONS: In this report, we demonstrate that efficacy, safety and PK profiles were comparable between etanercept 25 mg twice weekly and 50 mg once weekly in patients who had received at least 24 weeks of etanercept 25 mg twice weekly prior to receiving etanercept 50 mg once weekly in the extension study.     

Three-year registry data on biological treatment for psoriasis: the influence of patient characteristics on treatment outcome

Background The course of biological treatment in clinical practice may be highly different from treatment schedules in clinical trials. Treatment modifications and patient characteristics may influence treatment safety and efficacy. So far, long‐term results from the use of biological treatment in clinical practice are lacking. Objectives To report short‐ and long‐term efficacy and safety data on biologics, especially etanercept, used in daily clinical practice. Special attention has been paid to patient characteristics that may have influenced the response to therapy. Methods Prospectively collected registry data of all patients with psoriasis treated with biologics in the Radboud University Nijmegen Medical Centre outpatient clinic were used for analysis. Patient and treatment characteristics were surveyed. Efficacy and safety of etanercept for up to 3 years were analysed. Moreover, the influence of patient characteristics on etanercept treatment response was studied. Results The analysed cohort, consisting of 118 patients, went through 142 treatment episodes in total. Patients treated with biologics had an extensive medical history. Optimization of biological treatment was established in various ways, including treatment switches and introduction of concomitant therapies. Short‐term etanercept efficacy analysis showed a mean Psoriasis Area and Severity Index (PASI) improvement at week 24 of 59·7%. No significant influence of gender, age, baseline PASI, body mass index, number of previous systemic therapies or duration of psoriasis was found on week 24 efficacy results, although trends were discernible. The efficacy of etanercept remained stable for up to 156 weeks. Long‐term daily practice treatment with etanercept was only occasionally accompanied by major safety concerns. Conclusions The current study demonstrates that etanercept is able to improve psoriasis symptoms for a considerable time, and that serious side‐effects are infrequent. The influence of patient characteristics on treatment response is limited.     

Marked improvement in nail psoriasis during treatment with etanercept

Psoriasis is a chronic inflammatory skin condition that affects approximately 3% of the population. Up to 50% of patients with psoriasis have concurrent nail psoriasis, up to 30% of patients with skin psoriasis also have psoriatic arthritis and of these, approximately 80% have nail disease. The treatment of nail psoriasis is often challenging, and there is a need for new therapeutic options. Effective biological agents used in the treatment of moderate to severe chronic plaque psoriasis may represent a new therapeutic modality for this disease. A case of rapid improvement is reported in nail psoriasis under etanercept monotherapy with maintained efficacy following the withdrawal of continued therapy.     

Etanercept: Efficacy and safety

Objective  To evaluate the efficacy and safety of etanercept in the treatment of patients with moderate to severe plaque psoriasis.
Methods  An observational, longitudinal, and retrospective study involving two groups of dose of treatment with etanercept (50 vs. 100 mg/week). The selected patients presented moderate to severe plaque psoriasis, and they had received treatment with the mentioned drug. A total of 58 patients were included in the study. The efficacy of the drug was evaluated by measuring the psoriasis area and severity index (PASI), body surface area (BSA) and physician's global assessment (PGA) in weeks 8, 16, 24, 32, 40 and 48.
Results  A statistically significant improvement was observed in the PASI, BSA and PGA indexes after 24 and 48 weeks of therapy. As for PASI, and after 48 weeks of treatment, PASI 50, 75 and 90 were 100.0%, 92.3% and 69.2%, respectively. In our series, etanercept 50 mg/week reached the same results after 48 weeks as etanercept 100 mg/week, though the initial response was faster in the last group. The PASI, BSA and PGA indexes diminished significantly with the treatment, though without statistically significant differences between both groups. As for the safety, etanercept was well tolerated, and no serious adverse events were recorded. There were no cases of tuberculosis or opportunistic infections.
Conclusions  Our study confirms the efficacy and safety outcomes of the clinical trials of etanercept in psoriasis with both doses of treatment. As for the safety, etanercept was well tolerated, and all the recorded adverse events coincided with the known potential side-effects of treatment.

Conflicts of interest

None declared     

Juvenile generalized pustular psoriasis treated with etanercept

An 8‐year‐old boy with general pustular psoriasis (GPP) and iatrogenic secondary Cushing syndrome was treated successfully with etanercept after he had failed on acitretin, methotrexate, and methylprednisolone therapy. GPP is a severe and very rare variant of psoriasis in children often accompanied by life‐threatening complications. Retinoids, cyclosporine, methotrexate, or dapsone used in a small number of case series and case reports were effective. Etanercept is a recombinant human tumor necrosis factor‐alpha (TNF‐alpha) receptor protein fused with Fc portion of IgG1 that binds to TNF‐alpha, approved by Food and Drug Administration for the treatment of moderate‐to‐severe plaque psoriasis in children and teens who have not responded to other psoriasis treatments. In our patient, etanercept demonstrated significant clinical response associated with long‐term efficacy without acute exacerbation, excellent tolerability, and good safety profile.     

Combining etanercept with traditional agents in the treatment of psoriasis: a review of the clinical evidence

Psoriasis is a chronic, systemic inflammatory disorder manifesting primarily in skin and potentially in joints, frequently necessitating treatment with conventional systemic therapies, phototherapy or biological agents. Patients with moderate to severe disease suffer a diminished quality of life, experience significant comorbidities and have a higher mortality. Although traditional treatments are effective in the short‐term, their use is often limited by concerns over long‐term toxicity, including end‐organ damage and risk of malignancy. Combination therapy is a commonly used approach and is often more effective than any single agent. Lower doses of two treatments in combination can also minimize potential side effects from a single agent at higher doses. Etanercept is a recombinant human tumour necrosis factor (TNF)α receptor (p75) protein fused with the Fc portion of IgG1 that binds to TNFα. This article reviews the evidence on the efficacy and safety of etanercept in combination with methotrexate, acitretin, narrowband UVB and cyclosporin. The largest body of evidence assesses the combination with methotrexate, although evidence is available for the other combinations. Data suggest that although highly effective as monotherapy, etanercept in combination with a conventional systemic agent can enhance efficacy and allow drug sparing. Potentially, the combination may also result in faster treatment responses and permit safe transitioning from one systemic agent to another. Evidence to date suggests that these benefits can be achieved without significant additional toxicity, although long‐term data on the efficacy and safety of the combination in psoriatic populations is limited and further evaluation is warranted.     

Long-term data in the treatment of psoriasis

Moderate-to-severe plaque psoriasis is associated with a considerable disease burden and treatment needs are often unmet. Several conventional systemic drugs are available as treatments, including methotrexate, ciclosporin, retinoids and psoralen ultraviolet A, which, although effective, are associated with considerable toxicity that limits their long-term use. Recent developments in more targeted therapies involving biological agents, such as anti-T-cell agents and inhibitors of tumour necrosis factor-alpha, offer an alternative treatment approach with the possibility of longer continuous therapy, which may translate into disease control and improved quality of life. Although the majority of data supporting the use of biological agents have been obtained in short-term studies of 3–6 months' duration, some agents have been evaluated for longer periods of continuous administration. Comparison of efficacy among these agents may better define their role as long-term therapy. This article discusses the data currently available on both conventional and biological systemic therapies for psoriasis, in terms of short-term and long-term use.     

Reconsideration of 2008 decision: Food and Drug Administration approval of etanercept for systemic treatment of moderate to severe pediatric psoriasis

Although systemic etanercept was approved in 2004 for adults, the Food and Drug Administration (FDA) denied approval for use in children with psoriasis in 2008. Revision of the FDA's risk‐benefit assessment in response to understanding of disease burden, unmet medical need, and the effect of off‐label use in children with psoriasis led to the 2016 approval as the first systemic biologic product for the treatment of children aged 4‐17 with moderate to severe psoriasis. This article delineates the thinking that led to this reconsideration. The underlying thinking paved the way to inform current pediatric drug development as the FDA continues to bring needed medical products to children.