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Background: Continuous maintenance therapy with infliximab 5 mg kg(-1) every 8 weeks is effective for moderate-to-severe plaque-type psoriasis., Objectives: To evaluate the efficacy and safety of continuous vs. intermittent infliximab maintenance therapy., Methods: RESTORE2 was a long-term extension of RESTORE1. At baseline of RESTORE2, eligible patients who had received infliximab for 26 weeks and achieved Psoriasis Area and Severity Index (PASI) 75 in RESTORE1 were rerandomized 1 : 1 to continuous therapy (infliximab 5 mg kg(-1) every 8 weeks) or intermittent therapy (no infliximab until > 50% loss of PASI improvement). Safety and efficacy assessments occurred throughout the study., Results: In total, 222 patients were randomized to receive continuous therapy, and 219 to intermittent therapy. More serious infusion-related reactions occurred with intermittent therapy (8/219 patients, 4%) than with continuous therapy (1/222 patients, < 1%), leading the sponsor to terminate the study. The mean duration of exposure to infliximab was 40·12 weeks (SD 27·55) with a mean of 5·8 infusions (range 0-16) for continuous therapy and 22·78 weeks (SD 22·98) with a mean of 3·4 infusions (range 0-16) for intermittent therapy. Although no formal efficacy analyses were conducted, continuous therapy led to greater PASI 75 at week 52 in the continuous group (81/101, 80%) than in the intermittent group (39/83, 47%); several other efficacy measures demonstrated similar patterns., Conclusions: For patients with moderate-to-severe plaque-type psoriasis, continuous therapy with infliximab may be more effective than intermittent therapy. The incidence of serious infusion-related reactions in the intermittent group suggests that clinicians should avoid intermittent therapy in this population., (© 2013 British Association of Dermatologists.)

Basic research on psoriasis has identified a number of molecular targets which can be of therapeutic interest. While the first two biologics--alefacept and efalizumab--were developed primarily for dermatologists, other agents like cytokine antagonists (TNFα antagonists) were introduced primarily by other medical fields. Knowledge has provided new impulses for research, so that today many therapeutic strategies are being developed, not exclusively limited to biologics. Others branches of dermatology also have benefitted greatly from biologics like ipilimumab or omalizumab.

Background: Infliximab is indicated for treatment of moderate-to-severe plaque psoriasis in adults whose disease cannot be controlled with other systemic therapies, including methotrexate (MTX). To date, no studies have directly compared the efficacy and safety of infliximab and MTX., Objectives: To compare the efficacy and safety of infliximab vs. MTX in adults with moderate-to-severe plaque psoriasis., Methods: MTX-naïve patients (n = 868) were randomized 3:1 to receive infliximab 5 mg kg⁻¹ at weeks 0, 2, 6, 14 and 22 or MTX 15 mg weekly with a dose increase to 20 mg weekly at week 6 if the Psoriasis Area and Severity Index (PASI) response was < 25%. At week 16, patients with < PASI 50 response could switch treatment groups. The primary efficacy endpoint was PASI 75 response at week 16. Major secondary efficacy endpoints were PASI 75 response at week 26, and the proportion of patients achieving a Physician's Global Assessment (PGA) score of cleared (0) or minimal (1) at weeks 16 and 26. Others included Dermatology Life Quality Index, 36-Item Short Form Health Survey, and PGA, PASI 50, PASI 75 and PASI 90 responses over time., Results: The primary endpoint was achieved by a significantly greater proportion of infliximab-treated patients (508/653, 78%) than MTX-treated patients (90/215, 42%; P < 0·001). Key secondary endpoints also were achieved by a greater proportion of infliximab-treated patients. Similar responses were observed at week 26 in patients who switched from MTX to infliximab at week 16. Overall adverse event (AE) incidence was comparable between groups, but incidence of serious and severe AEs was slightly higher in the infliximab group., Conclusions: Infliximab was well tolerated and more efficacious than MTX in patients with moderate-to-severe plaque psoriasis. Infliximab also was efficacious in patients who failed MTX and switched to infliximab., (© 2011 The Authors. BJD © 2011 British Association of Dermatologists.)

The VEGF signaling pathway (including ligands, surface-bound receptors and intracellular downstream signaling cascades) is critically involved in angiogenesis under normal and pathological conditions, in particular in malignant tumors. As a consequence, several therapies that target specific components of this pathway have been approved for clinical use or are in various stages of clinical development. Currently, the monoclonal antibodies bevacizumab and ranibizumab, as well as the small-molecule kinase inhibitors sorafenib and sunitinib, have been approved for cancer therapy. The spectrum of cutaneous side effects elicited by bevacizumab is considerably less pronounced than that seen with EGF inhibitors and includes peripheral sensory neuropathy, stomatitis, skin dryness, skin discoloration and exfoliative dermatitis. In contrast, unwanted cutaneous side effects seen with the less specific small molecule compounds include pruritic exanthems, nail changes, cheilitis and the painful hand-foot-syndrome.

Palmoplantar pustular psoriasis (PPP) is a chronic inflammatory skin condition mainly characterized by recurrent eruptions of sterile pustules on erythematous skin; hyperkeratosis and fissures on the palms and soles are additional clinical features. Treatment options for PPP are unsatisfactory. We present a patient with a typical course of PPP that had previously received a broad range of topical and systemic antipsoriatic therapies. They all had to be discontinued due to ineffectiveness or side effects. Being aware of the high efficacy of infliximab in generalized pustular psoriasis, we initiated this therapy. An initial improvement was followed by a substantial flare after 7 months, during which a combination treatment of infliximab with methotrexate was administered. Only subsequent monotherapy with efalizumab led to complete clearing up of PPP after 10 to 12 weeks of treatment without any adverse effects. This indicates that efalizumab is potentially effective in PPP.

Adalimumab is the first fully human monoclonal antibody against TNFalpha and has been approved for treatment of rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis. Its efficacy for both joint and skin involvement has been confirmed in clinical trials. The recommended dose is 40 mg administered every other week subcutaneously. It may be combined with methotrexate and all topical psoriasis treatment modalities. User-friendly administration devices make self-injection possible. Patients should be evaluated for active/latent tuberculosis and serious infections prior to initiation of therapy. Adalimumab rapidly reduces joint symptoms within a few days. Adalimumab is used for the management of adult psoriatic arthritis patients who have had an inadequate response to disease-modifying antirheumatic drugs. Adalimumab is yet another biological for the treatment of psoriasis. Since the TNFalpha antagonists can be switched if one is ineffective, this agent broadens the therapeutic spectrum.

Morphological and functional properties of the eosinophilic granulocyte (e. G.) feature this haematopoietic stem cell-derived cell type as an important cellular component of defense mechanisms, immunologic reactions and proinflammatory/neoplastic processes. Over the last decade significant advances of the molecular pathophysiology of eosinophilic disorders enable increasingly the distinction between the more common reactive (secondary) and clonal eosinophilia including the hypereosinophilic syndrome. This review features a comprehensive clinical summary of dermatological disorders that are frequently associated with transient or persistent eosinophilia belonging to the reactive eosinophilia. The hypereosinophilic syndrome is a subset of idiopathic eosinophilia frequently associated with major tissue targets as skin, heart and others. Therefore, the hypereosinophilic syndrome has to be considered as important differential diagnosis. Most recently, the identification of selective targets (e. g. IL-5, CD52) has translated into therapeutic approaches with monoclonal antibodies such as mepolizumab, alemtuzumab or SCH55700.