Treatment of psoriasis with the chimeric monoclonal antibody against tumor necrosis factor alpha,infliximab

BACKGROUND: Psoriatic skin lesions in patients with Crohn's disease or psoriatic arthritis have shown improvement during infliximab treatment. OBJECTIVE: The purpose of our study was to systematically assess the effects of infliximab in patients with psoriatic skin lesions. METHODS: Eight patients with severe psoriasis were enrolled in an open-label clinical trial. Patients received infliximab, 5 mg/kg, intravenously at weeks 0, 2, and 6. The Psoriasis Area and Severity Index (PASI) was used to monitor disease activity at weeks 0, 2, 4, 6, 8, 10, and 14. Week 10 was the end point of the treatment phase; week 14 was the follow-up end point. Pruritus was assessed on a scale of 0 to 3. Histologic sections were prepared from biopsy specimens of uninvolved skin and of psoriatic lesions at weeks 0, 1, and 10 to measure epidermal thickness with the use of a microscopic micrometer grid. RESULTS: The PASI diminished from 21.8 +/- 4.2 (mean +/- SE) at week 0 to 3.4 +/- 2.0 at week 10, corresponding to 10.7% +/- 4.3% of the original values (100%); on follow-up at week 14, the PASI was 7.1 +/- 2.7 (or still 33.3% +/- 11.3% of the values at week 0). Pruritus decreased from 2.5 +/- 0.26 at week 0 to 0.43 +/- 0.2 at week 10 and to 0.83 +/- 11.3 at week 14. Likewise, epidermal thickness (acanthosis) tended to normalize from 0.41 +/- 0.06 mm at week 0 to 0.14 +/- 0.02 mm at week 10. No adverse effects other than fatigue during infusion on some occasions were reported. CONCLUSION: Although psoriasis tends to recur beyond 2 months of the infusions, this open study provides evidence that infliximab is an effective treatment.     

Chimeric monoclonal antibody to tumor necrosis factor alpha (infliximab) in psoriasis

BACKGROUND: Insights into the pathogenesis of psoriasis have provided opportunities to target key steps in the disease process. Tumor necrosis factor-alpha (TNF- alpha) being crucial to the pathogenesis of psoriasis, monoclonal antibodies against this cytokine have proved useful in its treatment. AIM: To study the efficacy of chimeric monoclonal antibody to TNF- alpha (infliximab) in Indian patients with recalcitrant psoriasis vulgaris. MATERIALS AND METHODS: Three patients with recalcitrant psoriasis vulgaris were studied. Baseline haemogram, biochemical parameters, chest radiograph and Mantoux skin test were performed. A loading dose regimen of 5 mg/kg infliximab was administered at weeks 0, 2 and 6. PASI assessment, adverse drug event monitoring and laboratory assessments were carried out at 2-week intervals until week 10. Patients were followed up until week 22 for relapse. RESULTS: Infliximab was well tolerated. The mean PASI was 25.4 at presentation and declined to 5.5 at 10 weeks. PASI 75 was attained at a mean of 9.6 weeks. Relapse occurred at a mean of 18.6 weeks after the first infusion. CONCLUSIONS: This study on Indian patients brings out the importance of cytokine-based therapies in psoriasis. Indigenous production could make these therapies a viable therapeutic option for psoriasis patients in the near future.     

Biologic therapy for psoriasis: the tumor necrosis factor inhibitors infliximab and etanercept

During the past several years, one of the major focuses in psoriasis research has been the development of novel biologic therapies for this disease. The aim of these therapies is to provide selective, immunologically directed intervention, with the hope that such specificity will result in fewer side effects than traditional therapies. In this 2-part review, we present an update on the progress of the 4 biologic agents that most likely will be the first available for clinical use: infliximab, etanercept, efalizumab, and alefacept. The structure and mechanism of each drug will be reviewed, as well as the most recent clinical experience and safety data. The first article of this review will focus on the therapies that inhibit tumor necrosis factor alpha (TNF-alpha).     

Combination therapy of cyclosporine and anti‐tumor necrosis factor α in psoriasis: a case series of 10 patients

Combination therapy has become important in treating psoriasis, using synergism between different mechanisms to maximize efficacy and minimize toxicity. Little has been published on the combination of cyclosporine and anti‐tumor necrosis factor (TNF) α agents. In this study, a retrospective chart review was made of the effects of this combination therapy in 10 patients with recalcitrant psoriasis. Treatment included a conditioning phase with cyclosporine, 3.14 ± 0.37 mg/kg for 4.6 ± 2 weeks, and a combination phase during which etanercept/adalimumab were initiated and cyclosporine was tapered over 10.2 ± 3.7 weeks. Treatment success, evaluated after each phase, was classified as complete recovery (CR, more than 75% improvement), partial response (PR, 25–75% improvement), and no response (NR, less than 25% improvement). All patients reached CR at the end of the combination therapy. Two were still on combination therapy after 12 and 20 weeks. Adverse event occurred in three cases, all in the conditioning phase. We conclude that combination therapy with cyclosporine and anti‐TNF α appears to offer an effective and safe approach to treatment of psoriasis.     

Treatment of severe recalcitrant plaque psoriasis with single-dose intravenous tumour necrosis factor-alpha antibody (infliximab)

Infliximab is a chimeric anti-tumour necrosis factor-alpha antibody that has been demonstrated to have marked efficacy in the treatment of psoriasis. Seven patients with chronic plaque psoriasis were treated with single-dose intravenous infliximab (5 mg/kg), and the Psoriasis Area and Severity Index (PASI) and Dermatology Life Questionnaire Index (DLQI) were used as a measure of treatment efficacy. There was an average improvement in PASI scores of 69% at 2 weeks post infusion. There was an improvement in DLQI of 61%. Four of the seven patients were also seen at 10 weeks post infusion and the improvement in PASI and DLQI was sustained. All patients tolerated the initial infusion well without adverse events. The results indicate that single-dose infliximab is an effective and efficacious therapy for recalcitrant psoriasis and has a prolonged therapeutic effect.     

Efficacy comparison of ustekinumab between anti‐tumor necrosis factor‐α drug‐naïve and anti‐tumor necrosis factor‐α drug‐resistant Japanese psoriasis cases

Ustekinumab is highly efficacious for psoriasis; however, it has not been fully clarified whether previous failure in anti‐tumor necrosis factor‐α (TNF‐α) therapy affects the treatment response with ustekinumab. Therefore, we evaluated the efficacy of ustekinumab in anti‐TNF‐α‐naïve and anti‐TNF‐α‐resistant cases and compared the clinical efficacies of adalimumab and ustekinumab in biologic naïve cases. Thirty‐five patients with plaque psoriasis who showed resistance to conventional therapies were enrolled; 26 patients, who had never been treated with biologics, were allocated to ustekinumab or adalimumab; nine patients who failed to achieve psoriasis area and severity index (PASI) 50 at week 16 with one or two TNF‐α antagonists were switched to ustekinumab. The end of the study was defined as 52 weeks after starting the first biologic for anti‐TNF‐α‐naïve patients and after switching to ustekinumab for anti‐TNF‐α‐resistant patients. The primary outcome measurement was the percentage of patients achieving PASI75 at week 16. In patients treated with ustekinumab, 87.5% of anti‐TNF‐α‐naïve and 77.8% of anti‐TNF‐α‐resistant cases achieved a PASI75 response at week 16, and no statistically significant difference was found between the treatment response rates (P = 0.60). When comparing the treatment efficacy of ustekinumab and adalimumab among anti‐TNF‐α‐naïve patients, there was also no statistically significant difference in PASI75 achievement rates (87.5 vs. 83.3%, P = 0.79). Our study suggests that ustekinumab can be considered as a first‐line biologic for psoriasis and a rescue therapy for anti‐TNF‐α‐resistant cases.     

Presence of antidrug antibodies correlates inversely with the plasma tumor necrosis factor (TNF)‐α level and the efficacy of TNF‐inhibitor therapy in psoriasis

Antidrug antibodies have been shown to be associated with a loss of response during biologic therapy. Despite the potential association, there has been no report on the simultaneous monitoring of the following parameters in psoriasis: presence of neutralizing antibodies, plasma tumor necrosis factor (TNF)‐α concentration, TNFi concentration and disease activity. Plasma concentrations of adalimumab, infliximab, etanercept and their respective antidrug antibodies, as well as plasma concentrations of TNF‐α were measured in 77 psoriasis patients receiving biologic therapy, and the values were correlated with the clinical activity of the skin disease. Antidrug antibodies were identified in the plasma of 25% of infliximab‐treated patients and 29.6% of adalimumab‐treated patients, but not in the etanercept group. Clinical severity scores were significantly higher in the antibody‐positive patients. In patients receiving infliximab or adalimumab therapy, the presence of antidrug antibodies was directly associated with reduced plasma TNF‐inhibitor concentration and elevated plasma TNF‐α level.     

The effectiveness of tumor necrosis factor alpha antibody (infliximab) in treating recalcitrant psoriasis: a report of 2 cases

BACKGROUND: Psoriasis is being recognized as an autoimmune disease in which immunocyte-derived cytokines are thought to drive the development of the altered keratinocyte phenotype. Although the role of tumor necrosis factor alpha (TNF-alpha) in psoriasis is not completely understood, it may underlie many of the key steps that lead to induction and maintenance of the disease. Infliximab is an immunoglobulin monoclonal antibody that binds and inactivates TNF-alpha and has been successfully used in the management of TNF-alpha-mediated diseases, such as Crohn disease and rheumatoid arthritis. OBSERVATIONS: Two patients with recalcitrant psoriasis that was unresponsive to multiple skin-directed and systemic therapies were treated with a single infusion of infliximab. The treatments resulted in rapid and complete clearing of psoriatic erythroderma and resolution of symptoms of arthritis in one case and complete clearing of widespread psoriatic plaques and improvement of symptoms of arthritis and inflammatory bowel disease in the other. The single treatments with infliximab were well tolerated with no immediate or long-term adverse effects noted. CONCLUSION: A single infusion of infliximab at 5 to 10 mg/kg resulted in the rapid and complete clearing of recalcitrant psoriatic plaques and erythroderma with a disease-free interval of 3 to 4 months in these 2 patients and improved the symptoms of psoriatic arthritis.     

Anti-tumor necrosis factor alpha monoclonal antibody (infliximab) for the treatment of Pyoderma gangrenosum associated with Crohn's disease

Here we report a case of Pyoderma gangrenosum (PG) associated with Crohn's disease successfully treated with infliximab. The efficacy of this drug in many inflammatory diseases has already been reported, but its use in PG has only been seen in very few cases. Our study confirms that this therapy is a valid alternative solution for treating PG, which is often unresponsive to conventional therapies.     

Treatment of pustular psoriasis with infliximab

Pustular psoriasis is a severe form of psoriasis with a generalized pustular eruption. Since TNF‐α plays an important role in pustular psoriasis, we treated two patients who had not responded to established therapy regimens with the TNF‐α antagonist infliximab. Both patients showed significant improvements of their skin eruption and their general condition within three days after treatment and without any side effects. We suggest that infliximab is a therapeutic option for severe therapy‐resistant pustular psoriasis because a single well‐tolerated dose significantly ameliorates the patient's condition.