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Systemic Agents (systemic + agent)
Selected AbstractsCombining etanercept with traditional agents in the treatment of psoriasis: a review of the clinical evidenceJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 10 2010PA Foley Abstract 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), receptor (p75) protein fused with the Fc portion of IgG1 that binds to TNF,. 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. [source] Efficacy and safety results from the randomized controlled comparative study of adalimumab vs. methotrexate vs. placebo in patients with psoriasis (CHAMPION)BRITISH JOURNAL OF DERMATOLOGY, Issue 3 2008J.-H. Saurat Summary Background, Biologic therapies such as adalimumab, a tumour necrosis factor antagonist, are safe and effective in the treatment of moderate to severe chronic plaque psoriasis. Objectives, To compare a biologic agent with methotrexate, a traditional systemic agent, to define clearly the role of biologics in psoriasis. Methods, Patients with moderate to severe plaque psoriasis were randomized to adalimumab (80 mg subcutaneously at week 0, then 40 mg every other week, n = 108), methotrexate (7·5 mg orally, increased as needed and as tolerated to 25 mg weekly; n = 110) or placebo (n = 53) for 16 weeks. The primary efficacy endpoint was the proportion of patients achieving at least a 75% improvement in the Psoriasis Area and Severity Index (PASI 75) after 16 weeks. Safety was assessed at all visits through week 16. Results, After 16 weeks, 79·6% of adalimumab-treated patients achieved PASI 75, compared with 35·5% for methotrexate (P < 0·001 vs. adalimumab) and 18·9% for placebo (P < 0·001 vs. adalimumab). Statistically significantly more adalimumab-treated patients (16·7%) than methotrexate-treated patients (7·3%) or placebo-treated patients (1·9%) achieved complete clearance of disease. The response to adalimumab was rapid, with a 57% improvement in mean PASI observed at week 4. Adverse events were similar across treatment groups. Adverse events leading to study discontinuation were greatest in the methotrexate group, primarily because of hepatic-related adverse events. Conclusions, After 16 weeks, adalimumab demonstrated significantly superior efficacy and more rapid improvements in psoriasis compared with either methotrexate or placebo. [source] Controversies in the management of the cutaneous T cell lymphomasDERMATOLOGIC THERAPY, Issue 5 2009John A. Zic ABSTRACT The primary cutaneous T cell lymphomas (CTCL) encompass all malignancies of the T cell where the skin is the primary organ of involvement. The diagnosis of a CTCL variant can be detoured by a number of obstacles including the slow evolution of the disease into a classic clinical and pathologic pattern. A realistic goal of early stage treatment is to reduce the likelihood of progression to a more advanced stage, not to achieve a cure. No studies have adequately compared the different systemic agents in patients with advanced CTCL so the clinician is left to act in the best interest of the patient with what evidence is available. When using the systemic agents, a "start low and go slow" strategy may offer patients several advantages. Dermatologists are uniquely trained to diagnose and to manage all but the most advanced stage patients with CTCL. [source] Adalimumab for treatment of moderate to severe psoriasis and psoriatic arthritisDERMATOLOGIC THERAPY, Issue 2008M. R. Bongiorno ABSTRACT: Psoriasis and psoriatic arthritis are common diseases associated with considerable morbidity and disability. Their pathophysiology comprises similar processes leading to inflammation of skin, entheses, and joints. Although traditional systemic agents can be effective, their use may be limited by lack of efficacy and concerns regarding adverse effects. The objective of this study was to assess the efficacy and safety of adalimumab, a fully human antitumor necrosis factor (anti-TNF) monoclonal antibody, over 16 weeks. The present authors report their personal experience in 15 patients with severe plaque psoriasis and psoriatic arthritis, refractory to other treatments, in which a decisive regression of joint/skin involvement was obtained. Psoriasis and psoriatic arthritis are chronic inflammatory disorders resulting from a combination of genetic and environmental factors. [source] A retrospective analysis of treatment responses of palmoplantar psoriasis in 114 patientsJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 7 2009Abstract Background, Treatment options remain unsatisfactory for patients with palmoplantar psoriasis (PP) and palmoplantar pustular psoriasis (PPP). Aim, To evaluate the therapeutic responses of PP and PPP patients that were treated in our psoriasis polyclinic between 2003 and 2007. Methods, This retrospective study comprised PP (n = 62) and PPP (n = 52) patients. Treatments were individualized according to patient compliance and associating systemic diseases. The effect of systemic treatments was grouped as follows: ,no improvement': patients unresponsive for the present treatment; ,partial improvement': < 50% decrease in severity or affected area; ,moderate improvement': 50,75% decrease in severity or affected area, and ,marked improvement': > 75% decrease of the disease compared to baseline. Results, In the PP group, 17 of 62 patients showed marked improvement to topical agents, while the remaining patients required systemic agents including oral retinoids (n = 24), local psoralen plus ultraviolet A (PUVA; n = 12), methotrexate (n = 9) and cyclosporine (n = 2). Marked improvement was achieved in 53%, 45%, 47% and 100%, respectively. In these patients, two (n = 10), three (n = 5), or four (n = 5) systemic agents were used alternately. In the PPP group, 18 of 52 patients achieved marked improvement by topical agents. Patients that required systemic agents were treated with colchicum (n = 19), local PUVA (n = 8), methotrexate (n = 4), oral retinoids (n = 3) and cyclosporine (n = 2). These treatments achieved a marked improvement in 60%, 33%, 57%, 83%, and 50% of the patients, respectively. In the course of the disease, 18 patients required two and 3 patients required three systemic agents alternately. Conclusions, Although the success rates appeared to be high, the high number of patients who required multiple systemic agents emphasized the fact that localized forms of psoriasis were resistant to therapy. Conflicts of interest None declared [source] Review article: the management of heartburn in pregnancyALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 9 2005J. E. RICHTER Summary Heartburn is a normal consequence of pregnancy. The predominant aetiology is a decrease in lower oesophageal sphincter pressure caused by female sex hormones, especially progesterone. Serious reflux complications during pregnancy are rare; hence upper endoscopy and other diagnostic tests are infrequently needed. Gastro-oesophageal reflux disease during pregnancy should be managed with a step-up algorithm beginning with lifestyle modifications and dietary changes. Antacids or sucralfate are considered the first-line drug therapy. If symptoms persist, any of the histamine2 -receptor antagonists can be used. Proton pump inhibitors are reserved for women with intractable symptoms or complicated reflux disease. All but omeprazole are FDA category B drugs during pregnancy. Most drugs are excreted in breast milk. Of systemic agents, only the histamine2 -receptor antagonists, with the exception of nizatidine, are safe to use during lactation. [source] Practical Considerations in Acne Treatment and the Clinical Impact of Topical Combination TherapyPEDIATRIC DERMATOLOGY, Issue 2008Andrew C. Krakowski M.D. The effects of acne are profound both physically and psychosocially across all age groups and ethnicities; therefore, prompt recognition and appropriate treatment are critical. Pharmacotherapeutic approaches range from simple monotherapy to multimodal treatments with a variety of topical and systemic agents. Optimal patient outcomes in acne management, however, are based both on treatment efficacy as well as overall patient satisfaction. In an effort to comprehensively address these key clinical considerations in acne management, we examine the diverse nature of acne patients, the factors in optimizing treatment outcomes, and the clinical impact of current medications, particularly topical combination therapy. [source] Successful treatment of lymphomatoid papulosis with photodynamic therapyAUSTRALASIAN JOURNAL OF DERMATOLOGY, Issue 2 2009Michelle Rodrigues ABSTRACT A 40-year-old woman presented with a prolonged history of recurrent crops of erythematous papules and nodules on her abdomen, arms and legs. Histological examination of a cutaneous biopsy revealed Type A lymphomatoid papulosis. Over a 3-year period, some of the patient's lesions had proven to be resistant to treatment with topical and intralesional corticosteroids and systemic agents including methotrexate, tetracycline and nicotinamide. These resistant lesions were treated with two sessions of methyl aminolevulinate photodynamic therapy given 1 week apart. Review 11 months post-photodynamic therapy demonstrated complete clinical clearance at the treatment site. While photodynamic therapy is considered a standard non-surgical treatment option for non-melanoma skin cancers and has been described in a number of non-oncological indications, this is the first report of its use in lymphomatoid papulosis. [source] Advanced-stage renal cell carcinoma treated by radical nephrectomy and adjacent organ or structure resectionBJU INTERNATIONAL, Issue 2 2009Michael E. Karellas OBJECTIVE To examine the effect of radical nephrectomy (RN) with adjacent organ and structure resection on survival, as invasion of adjacent organs in patients with renal cell carcinoma (RCC) is rare. PATIENTS AND METHODS After institutional review board approval, we reviewed our database and statistically analysed of patients with pathological stage T3 or T4 RCC who had RN and resection of a contiguous organ or structure. RESULTS We identified 38 patients of 2464 (1.5%) who had RN with adjacent organ or structure resection. The median (interquartile range) size of the mass was 11 (8,14) cm, and the follow-up 13 (5,33) months. Most patients (68%) were pT4 stage and had conventional clear cell carcinoma (95%). Fourteen patients (37%) had positive surgical margins. The liver (10) was the most commonly resected adjacent organ or structure. Only one patient remains alive with no evidence of disease at 5 years, while three are currently alive with disease. Overall, 34 of 38 patients (90%) ultimately died from disease at a median (range) of 11.7 (5.4,29.2) months after surgical resection. The surgical margin status was the only statistically significant factor for recurrence and death (P = 0.006). CONCLUSIONS The prognosis for patients with advanced RCC and adjacent organ or structure involvement is extremely poor and similar to that of patients with metastatic disease. These patients should be thoroughly counselled about the impact of surgical management and considered for entry into neoadjuvant or adjuvant clinical trials with new targeted systemic agents. [source] Fumaric acid esters in severe psoriasis, including experience of use in combination with other systemic modalitiesBRITISH JOURNAL OF DERMATOLOGY, Issue 4 2004P. Balasubramaniam Summary Background Fumaric acid esters (FAE) are used as a systemic treatment for severe psoriasis in Germany but there has been only very little published experience from the U.K. The potential for use in combination with other systemic drugs has not been explored. Objectives To present data relating to the efficacy of FAE in severe psoriasis and to examine the potential dose-sparing effect and safety issues when FAE are combined with other systemic agents. Methods We retrospectively analysed the records of patients who had received FAE for severe psoriasis either alone (in two cases) or along with other systemic medications (in 10 cases). We reviewed the efficacy of FAE and assessed whether dose reductions were achieved for other systemic drugs. Patients were monitored carefully for possible adverse effects. Results Of 12 patients treated with FAE one discontinued the drug very early, due to flushing, while on a very low dose. The other 11 patients all demonstrated an improvement in psoriasis after starting FAE. Nine patients received FAE in combination with other systemic therapies including ciclosporin, acitretin, hydroxyurea and methotrexate. Seven achieved useful overall reductions in the dose of the other drugs. In two patients severe psoriasis was controlled using FAE alone. The side-effect profile of FAE was similar to that previously reported. There was no evidence of drug interactions. Conclusions FAE appear effective and less toxic than other systemic treatments for psoriasis. FAE were used successfully in combination with other systemic agents and generally enabled the doses of the more hazardous drugs to be reduced. Extremely careful monitoring is required when using FAE in such combined regimens as experience is currently very limited. [source] Onychomycosis in clinical practice: factors contributing to recurrenceBRITISH JOURNAL OF DERMATOLOGY, Issue 2003R.K. Scher Summary The treatment of onychomycosis has improved in recent years and many patients can now expect a complete and lasting cure. However, for up to 25% of patients, persistent disease remains a problem, thus presenting a particular challenge to the clinician. For these patients, it is obviously important to ensure that a correct diagnosis of onychomycosis has been made, as misdiagnosis will inevitably jeopardize the perception of therapeutic effectiveness. Although onychomycosis accounts for about 50% of all nail diseases seen by physicians, nonfungal causes of similar symptoms include repeated trauma, psoriasis, lichen planus, local tumours vascular disorders and inflammatory diseases. Predisposing factors that contribute to a poor response to topical and/or oral therapy include the presence of a very thick nail, extensive involvement of the entire nail unit, lateral nail disease and yellow spikes. However, poor penetration of systemic agents to the centre of infection, or the inability of topical agents to diffuse between the surface of the nail plate and the active disease below, probably contributes to this. Other factors contributing to recurrence may be related to the patient's family history, occupation, lifestyle or underlying physiology. In addition, patients with concomitant disease (e.g. peripheral vascular disease, diabetes) or patients who are immunosuppressed (e.g. those with human immunodeficiency virus/acquired immunodeficiency syndrome) are more susceptible to onychomycosis. In the elderly, the prevalence of onychomycosis may be as high as 60%, and increases with age; in this population, physical trauma plays a major role in precipitating recurrence, especially in patients with faulty biomechanics due to underlying arthritis and bone abnormalities. It is also possible that recurrence in some cases is due to early termination of treatment or use of an inappropriate dose, and these possibilities should be eliminated before further investigations are undertaken. ,There is good evidence to suggest that a combination of oral and topical therapies, when given at the same time, yield excellent clinical outcomes, although there remains a need for more effective topical agents with greater nail penetration and more effective oral antifungal agents. [source] Hyperthermic intraperitoneal intraoperative chemotherapy after cytoreductive surgery for the treatment of abdominal sarcomatosisCANCER, Issue 9 2004Clinical outcome, prognostic factors in 60 consecutive patients Abstract BACKGROUND Abdominal sarcomatosis is a rare nosologic entity with a poor prognosis. After a Phase I study on cytoreductive surgery combined with hyperthermic intraperitoneal intraoperative chemotherapy (HIIC), the authors reported the results of the treatment of 60 patients using this novel multimodal approach. METHODS Twenty-nine patients had multifocal primary disease and 31 patients had recurrent abdominal sarcoma. Tumor histology was represented by visceral (n = 26 [43%]) and retroperitoneal (n = 34 [57%]) sarcoma. All patients underwent cytoreductive surgery (with no or minimal residual disease) and 90-minute HIIC with doxorubicin (15.25 mg/L of perfusate) and cisplatin (43 mg/L). The clinical outcome and the prognostic value of 11 clinicopathologic variables were analyzed. RESULTS No postoperative deaths occurred. The morbidity rate was 33% and the moderate to severe locoregional toxicity rate was 15%. The median time to local disease progression and the median overall survival were 22 months and 34 months, respectively. Using multivariate analysis, histologic grading and completeness of surgical cytoreduction predicted patient prognosis, indicating that both local progression-free and overall survival were affected significantly by tumor aggressiveness and local disease control. CONCLUSIONS Although these results were encouraging, there was no definitive conclusion reached regarding the therapeutic activity of this locoregional treatment. In addition, the toxicity rate was substantial. In the absence of effective systemic agents, the therapeutic potential of cytoreductive surgery plus HIIC should be explored further in comparative trials. Cancer 2004. © 2004 American Cancer Society. [source] Fumaric acid esters in the management of severe psoriasisCLINICAL & EXPERIMENTAL DERMATOLOGY, Issue 3 2007L. Brewer Summary Background., Fumaric acid esters (FAEs) offer an effective alternative to patients with psoriasis in whom other systemic agents are contraindicated or have failed. Objective., We assessed the efficacy and side effect profile of FAEs in a group of patients with psoriasis. Methods., A retrospective study was carried out on patients treated with FAEs over 21 months. Information was gathered from patients' notes. Dosage, response and side effects were recorded. Results., In total, 31 patients were included. The mean age was 46.8 years. All patients had been treated with other modalities and 61.5% had received previous systemic treatment. There was good to excellent response in 58.6% of patients. Subjective side-effects were common (87.1%), and lymphopenia occurred in 61.3%. The drug was not tolerated by one-fifth of patients. Conclusion., The relatively low toxicity and absence of hepatotoxicity makes FAEs a reasonable first-line systemic treatment in selected patients with difficult psoriasis. [source] Management of severe adult atopic dermatitisCLINICAL & EXPERIMENTAL DERMATOLOGY, Issue 4 2002Nicholas Reynolds In common with many units, we run a specialist atopic eczema clinic that receives both secondary and tertiary referrals. Investigation into possible provoking factors includes RAST testing and patch testing where appropriate. The mainstay of treatment for moderate to severe atopic eczema remains topical steroids and emollients. Our specialist nurses play a key role in education and in particular demonstrating topical treatments , including bandaging. It is surprising that many patients have not previously been shown how to apply the treatments prescribed. Nevertheless, despite optimizing topical treatment protocols, a proportion of patients require hospital admission or second-line therapy. Our recent double-blind, randomized, controlled trial of narrow-band UVII vs. UVA (as used in PUVA) vs. placebo has confirmed that narrow-band WB phototherapy is an effective adjunctive treatment in moderate to severe atopic eczema. This trial also highlighted the value of recording disease activity (e.g. SASSAD) in individual patients following a change of therapy. UVA1 may be useful for acute severe atopic eczema but this UV source is only available in limited centres within the UK. Selected resistant patients or patients with acute flares are considered for short-term cyclosporin therapy. Azathioprine is widely used by consultant dermatologists in the UK as a second-line agent , despite the lack of evidence of efficacy. We are currently conducting a randomized placebo-controlled trial to address this issue. The importance of checking thiopurine methyl transferase (TPMT) prior to initiating azathioprine therapy has been emphasized. Our pilot data, with a dosage regime based on the TPMT result, suggest that patients may achieve a longer-term remission after a relatively short course. Mycophenolate mofetil has been reported to be effective in an open trial and methotrexate is also used but there is a lack of published evidence. The advent of topical tacrolimus and ascomycins, which have been shown to be effective in controlled trials, appear to be a promising development in the management of patients with moderate to severe atopic eczema and may lead to reduction in the use of systemic agents. [source] | ||||||||||