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Biologic Therapy (biologic + therapy)

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Medical Sciences	100%

Selected Abstracts

Characteristics of patients with rheumatoid arthritis presentingfor physiotherapy management:A multicentre study

MUSCULOSKELETAL CARE, Issue 1 2007
Grad Dip Statistics, Norelee Kennedy BSc (Physio)
Abstract Objectives:,To describe the characteristics of patients with rheumatoid arthritis (RA) attending for physiotherapy management in Ireland. Methods:,Managers of physiotherapy departments in the 53 hospitals in Ireland were invited to participate in a multi-centre observational study over a 6-month period. Data on patients with RA the day of presentation for physiotherapy management were recorded. These data related to patient demographic details, disease management, aids and appliances, splint and orthoses usage and occupational issues. The Health Assessment Questionnaire was also recorded for each patient. Results:,A total of 273 patients from eight physiotherapy departments participated in the survey (n = 199; 73% female). Mean age of the participants was 59.3 (SD 12.5) years with mean disease duration of 13.8 (SD 10.6) years. The majority of the patients were inpatients (n = 170, 62%). Sixty-eight per cent of patients had attended for previous physiotherapy treatment and 98% were under current rheumatologist care. Biologic therapies were prescribed to 11% of patients. Use of splint and foot orthoses was high with 133 patients (49%) wearing splints and 75 (31%) wearing foot orthoses. The majority of patients had moderate (n = 119, 44%) or severe (n = 94, 35%) disability as per Health Assessment Questionnaire (HAQ) score. Mean HAQ score was 1.5, with HAQ scores showing increasing disability with increasing age, disease duration and erythrocyte sedimentation rate (ESR) levels. Conclusions:,Patients with RA attending for physiotherapy management present with varied profiles. This study provides valuable information on the characteristics of patients with RA attending for physiotherapy management which will contribute to physiotherapy service planning and delivery and will optimize patient care. Copyright © 2006 John Wiley & Sons, Ltd. [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 2008
J.-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]

Biologic therapy in the management of extraintestinal manifestations of inflammatory bowel disease

INFLAMMATORY BOWEL DISEASES, Issue 11 2007
Arthur Barrie MD
Abstract The inflammatory bowel diseases (IBD), notably Crohn's disease (CD) and ulcerative colitis (UC), are systemic inflammatory diseases primarily involving the gastrointestinal tract. Twenty percent to 40% of patients with IBD develop extraintestinal inflammation and symptoms, known as extraintestinal manifestations (EIMs).1,7 The most common EIMs affect the joints, skin, eyes, and biliary tract. The EIMs associated with IBD bear a negative impact on patients with UC and CD. Thus, the successful treatment of EIMs is essential for improving the quality of life of IBD patients. For most EIMs, their resolution often parallels that of the active IBD in both timing and therapy required. However, some EIM such as axial arthritis, pyoderma gangrenosum, uveitis, and primary sclerosing cholangitis run a clinical course independent of IBD disease activity. The advent of biologic response modifiers, e.g., tumor necrosis factor-, (TNF) inhibitors, has improved the treatment of IBD and its associated EIMs. This article reviews the therapeutic experiences of the 2 most widely used anti-TNF neutralizing antibodies, infliximab and adalimumab, for immune-mediated EIM of IBD. (Inflamm Bowel Dis 2007) [source]

Chronic inflammatory demyelinating polyneuropathy associated with tumor necrosis factor-, antagonists

MUSCLE AND NERVE, Issue 5 2010
Amer Alshekhlee MD
Abstract Biologic therapy with tumor necrosis factor (TNF)-, antagonists for rheumatoid arthritis has been well established. We describe two patients with rheumatoid arthritis who developed chronic inflammatory demyelinating polyneuropathy (CIDP) during their course of therapy with TNF-, antagonists. A 45-year-old woman and a 49-year-old man, both with a history of rheumatoid arthritis, were treated with etanercept and infliximab, respectively. Clinical signs of peripheral neuropathy developed 2 weeks and 12 months after the initiation of TNF-, antagonists. Electrodiagnostic studies at variable points during the disease course showed signs of acquired demyelination consistent with CIDP. Cerebrospinal fluid examination showed albuminocytologic dissociation (total protein concentration 118 mg/dl and 152 mg/dl, respectively). Both patients failed to improve after discontinuation of the offending agent, and they responded poorly to corticosteroids. However, there was clinical and electrophysiologic recovery after initiation of intravenous immunoglobulin (IVIg) therapy. CIDP may occur early or late during the treatment course with TNF-, antagonists. IVIg may reverse and stabilize the inflammatory process. Muscle Nerve 41: 742,747, 2010 [source]

A survey of foot problems in juvenile idiopathic arthritis

MUSCULOSKELETAL CARE, Issue 4 2008
G. Hendry BSc(Hons)
Abstract Background:,Evidence suggests that foot problems are common in juvenile idiopathic arthritis (JIA), with prevalence estimates over 90%. The aim of this survey was to describe foot-related impairment and disability associated with JIA and foot-care provision in patients managed under modern treatment paradigms, including disease-modifying anti-rheumatic drugs (DMARDs) and biologic therapies. Methods:,The Juvenile Arthritis Foot Disability Index (JAFI), Child Health Assessment Questionnaire (CHAQ), and pain visual analogue scale (VAS) were recorded in 30 consecutive established JIA patients attending routine outpatient clinics. Foot deformity score, active/limited joint counts, walking speed, double-support time (s) (DS) and step length symmetry index % (SI) were also measured. Foot-care provision in the preceding 12 months was determined from medical records. Results:,Sixty-three per cent of children reported some foot impairment, with a median (range) JAFI subscale score of 1 (0,3); 53% reported foot-related activity limitation, with a JAFI subscale score of 1 (0,4); and 60% reported participation restriction, with a JAFI subscale score of 1 (0,3). Other reported variables were CHAQ 0.38 (0,2), VAS pain 22 (0,79), foot deformity 6 (0,20), active joints 0 (0,7), limited joints 0 (0,31), walking speed 1.09,m/s (0.84,1.38,m/s), DS 0.22,s (0.08,0.26,s) and SI ±4.0% (±0.2,±31.0%). A total of 23/30 medical records were reviewed and 15/23 children had received DMARDS, 8/23 biologic agents and 20/23 multiple intra-articular corticosteroid injections. Ten children received specialist podiatry care comprising footwear advice, orthotic therapy and silicone digital splints together with intrinsic muscle strengthening exercises. Conclusion:,Despite frequent use of DMARD/biologic therapy and specialist podiatry-led foot care, foot-related impairment and disability persists in some children with JIA. Copyright © 2008 John Wiley & Sons, Ltd. [source]

Positioning biologic agents in the treatment of Crohn's disease,

INFLAMMATORY BOWEL DISEASES, Issue 10 2009
Stephen B. Hanauer MD
Abstract One decade after the emergence of biologic therapy for Crohn's disease (CD), our treatment algorithms are beginning to change. Once reserved for patients with refractory disease, disease unresponsive to conventional therapies, or those requiring multiple courses of corticosteroids, there is increasing evidence that early, aggressive interventions with immunosuppressants or biologic therapies targeting tumor necrosis factor-, or ,-4 integrins can alter the natural history of CD by reducing the transmural complications of structuring and fistulization and the nearly inevitable requisite for surgical resections. More recent trials are beginning to suggest that intervention with combination therapy for selected patients with a poor prognosis may modify the long-term course of CD. Selection of patients with features predicting a complex or progressive course and early, combined intervention is now possible. Future studies are still needed to best identify predictors of response to individual agents with differing mechanisms of action, as well as to optimize the risk-benefit of long-term maintenance therapy. (Inflamm Bowel Dis 2009) [source]

An analysis of the placebo effect in Crohn's disease over time

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 1 2010
W. C. GALLAHAN
Summary Background, Randomized, placebo controlled trials are used to assess the efficacy of therapies for Crohn's disease. The placebo response and remission rates vary among studies. Aim, To analyse how the placebo response and remission rates in Crohn's trials have changed over time in the era of parenteral biologic therapies. Methods, A search for randomized, placebo-controlled trials of parenteral biologic therapies for active Crohn's disease was conducted using online databases. The placebo response and remission rates and study week of evaluation were recorded for each trial. The placebo response and remission rates were analysed as functions of publication date and study week of evaluation. Results, The odds of a placebo-induced remission and response significantly increased as the week of evaluation increased. The placebo remission rate increased significantly with year of publication. Adjusted for week of evaluation, this increase in placebo remission rate over time was no longer significant. The increase in the placebo response over this time period was not statistically significant. Conclusion, The observed increase in placebo remission rates over time in trials of parenteral biologic therapies in Crohn's disease is explained by longer times to the primary endpoint in more recent trials. [source]

A survey of foot problems in juvenile idiopathic arthritis

The LUNDEX, a new index of drug efficacy in clinical practice: Results of a five-year observational study of treatment with infliximab and etanercept among rheumatoid arthritis patients in southern Sweden

ARTHRITIS & RHEUMATISM, Issue 2 2006
Lars Erik Kristensen
Objective To describe the use of the LUNDEX, a new index for comparing the long-term efficacy and tolerability of biologic therapies in rheumatoid arthritis (RA) patients treated in clinical practice. Methods Patients (n = 949) with active RA that had not responded to at least 2 disease-modifying antirheumatic drugs (DMARDs) including methotrexate, in whom biologic therapy was being initiated, were included in a structured clinical followup protocol. The protocol included collection of data on diagnosis, disease duration, previous and ongoing DMARD treatment, and dates on which biologic treatment was started and terminated. In addition, data on efficacy measures used for calculating validated response criteria, i.e., the European League Against Rheumatism and American College of Rheumatology response criteria, were collected at fixed time points. Data were prospectively registered from March 1999 through January 2004. The LUNDEX, a new index combining the proportion of patients fulfilling a selected response criteria set with the proportion of patients adhering to a particular therapy, was designed to compare the efficacy of the different therapies. Results Etanercept had higher overall LUNDEX values compared with infliximab, mostly because of a lower rate of adherence to therapy with infliximab. The relationship between the drugs was consistent irrespective of the response criteria used. Conclusion The LUNDEX is a valuable tool for evaluating drug efficacy in observational studies. It has the advantage of integrating clinical response as well as adherence to therapy in a composite value. Moreover, the LUNDEX has a practical and potentially universal application independent of diagnosis and response criteria. [source]

HER-2/neu overexpression in patients with radically resected nonsmall cell lung carcinoma

CANCER, Issue 10 2002
Impact on long-term survival
Abstract BACKGROUND Using immunohistochemistry, the authors prospectively investigated the expression of HER-2/neu protein in radically resected specimens of nonsmall cell lung carcinoma (NSCLC) and evaluated its impact on long-term prognosis. METHODS Between January 1991 and February 1992, surgical specimens from 130 consecutive patients who underwent radical resection for NSCLC (60 squamous cell carcinoma, 48 adenocarcinoma cases, and 22 large cell carcinomas) and that were staged (according to the TNM staging system) pathologically as Stage I (41 cases [ 32%]), Stage II (37 cases [28%]), and Stage IIIA (52 cases [40%]) were investigated for the expression of HER-2/neu using an avidin-biotin complex immunohistochemical technique. A semiquantitative four-stage grading system was used (0%, 1,5%, 6,20%, and > 20% positive cells) and an average number of 1500 cells/section was considered. Data were correlated with clinical and pathologic variables. RESULTS Normal bronchial tissue was found to be completely negative for HER-2/ neu expression whereas 21 of the 130 tumor specimens (16%) were positive (range 1,> 20%). HER-2/neu positivity did not appear to differ significantly among pathologic stages and histotypes. Using a predetermined cutoff value of 5% positive cells, 15 tumor specimens (12%) were found to be above this value. The median survival time (85 weeks vs. 179 weeks) and overall survival rate were significantly lower in patients with > 5% HER-2/neu -positive tumors (hazard ratio for the group with > 5% positive cells: 2.94, 95% confidence interval, 1.62,5.34; P < 0.0004). On multivariate analysis, HER-2/ neu and extent of tumor emerged as independent factors for disease-related mortality. CONCLUSIONS In NSCLC, the negative impact of HER-2/neu overexpression on survival was maintained in the long-term follow-up of radically resected patients. HER-2/neu overexpression may be a valuable prognostic factor as well as a potential target for biologic therapies. Cancer 2002;94:2669,74. © 2002 American Cancer Society. DOI 10.1002/cncr.10531 [source]

1365: Immunosuppressors and biologic agents

ACTA OPHTHALMOLOGICA, Issue 2010
AD DICK
Purpose To overview the contemporary therapeutic approaches to treatment of non-infectious non-infective ocular inflammatory disease. Treatment of non-infectious uveitis has over past 15 years expanded from the use of traditional therapies including corticosteroids and immunosuppressants to the deployment of targetting the immune response with biologic therapies with monoclonal antibodies and immunoadhesins. Methods The talk will overview the evidence of effect of immunosuppressants in the treatment of uveitis, the role of predicting steroid responsiveness, the use of monotherapy with immunosuppression and finally the pathways and evidence of success of biologic therapy. Results The concommitant use of immunosuppression is an important aspect to the adequate treatment of uveitis. This ensures adequate control of inflammation whilst reducing the need for comcomitant steroids thereapy. Moreover, monotherapy is equally efficacious in the control of some forms of uveitis. Neverthless there are patients who remain refractory to therapy, and in particular treatment of sight threatening Cystoid macular oedema. The use of targetted biologic therapy has gained increasing evidence to now lead to clinical trials in the use of anti-TNF and anti-IL17 agents. Conclusion There is now a recognised algorithm to treat aggressively and early patients with sight threatening disease. The appropriately timed use of immunosuppression and moreover increasingly earlier intervention with biologics has the promise to alter prognosis and outcome of such blinding disorders. [source]

Positioning biologic agents in the treatment of Crohn's disease,

Management and prevention of postoperative Crohn's disease

INFLAMMATORY BOWEL DISEASES, Issue 10 2009
Miguel Regueiro MD
Abstract Postoperative Crohn's disease (CD) recurrence is a common occurrence after intestinal resection. Currently, the optimal management of patients who have undergone surgical resection is unknown and treatment remains subjective. Clinicians in conjunction with patients must balance the risks of recurrence against the potential risks associated with treatment. For those at very low risk of recurrence, no therapy may be needed; however, for patients at moderate risk immunomodulators should be considered. For those at highest risk of recurrence, biologic therapy, specifically antitumor necrosis factor agents, have emerged as appropriate treatment. Any postoperative management strategy should include a colonoscopy 6,12 months after surgery to identify recurrence. This review discusses current evidence for various pharmacologic approaches in the prevention of postoperative recurrence and provides guidance for clarifying patient risk. (Inflamm Bowel Dis 2009) [source]

Clinical Experience with Trastuzumab (Herceptin)

THE BREAST JOURNAL, Issue 6 2003
Charles L. Vogel MD
Abstract: Trastuzumab is a humanized monoclonal antibody against the epidermal growth factor family oncogene, Her-2/neu. It has revolutionized therapy for the 15,20% of patients with metastatic breast cancer whose tumors have gene amplification for Her-2/neu. Results of clinical trials with single agent trastuzumab and in combination with paclitaxel, docetaxel, vinorelbine, gemcitabine and platinum salts have been encouraging. Durable remissions in excess of 5 years have occasionally been reported. Subjectively the side effect profile of this novel, targeted therapy, has been mild. Cardiac toxicity, while reported in combination regimens with anthracyclines tend to be easily manageable and not absolute contradictions to continuation of trastuzumab. Outside of clinical trials, however, anthracycline/trastuzumab combinations should be avoided. Preliminary results of trials with various combinations of chemotherapeutic agents have been promising while combinations with hormonal and other biologic therapy are ongoing. Trastuzumab is an exciting new monoclonal antibody with interesting anti-tumor activity in patients with Her-2/neu gene amplified breast cancer. We look forward to ongoing clinical trials combining trastuzumab with a broad array of other chemotherapeutic, hormonal and biological agents. [source]

The LUNDEX, a new index of drug efficacy in clinical practice: Results of a five-year observational study of treatment with infliximab and etanercept among rheumatoid arthritis patients in southern Sweden

Direct medical costs and their predictors in patients with rheumatoid arthritis

ARTHRITIS & RHEUMATISM, Issue 10 2003
527 patients, A three-year study of
Objective To estimate total direct medical costs in persons with rheumatoid arthritis (RA) and to characterize predictors of these costs. Methods Patients (n = 7,527) participating in a longitudinal study of outcome in RA completed 25,050 semiannual questionnaires from January 1999 through December 2001. From these we determined direct medical care costs converted to 2001 US dollars using the consumer price index. We used generalized estimating equations to examine potential predictors of the costs. Monte Carlo simulations and sensitivity analyses were performed to evaluate the varying prevalence and cost of biologic therapy. Results The mean total annual direct medical care cost in 2001 for a patient with RA was $9,519. Drug costs were $6,324 (66% of the total), while hospitalization costs were only $1,573 (17%). Approximately 25% of patients received biologic therapy. The mean total annual direct cost for patients receiving biologic agents was $19,016 per year, while the cost for those not receiving biologic therapy was $6,164. RA patients who were in the worst quartile of functional status, as measured by the Health Assessment Questionnaire, experienced direct medical costs for the subsequent year that were $5,022 more than the costs incurred by those in the best quartile. Physical status as determined by the Short Form 36 physical component scale had a similar large effect on RA costs, as did comorbidity. Medical insurance type played a more limited role. However, those without insurance had substantially lower service utilization and costs, and health maintenance organization patients had lower drug costs and total medical costs. Increased years of education, increased income, and majority ethnic status were all associated with increased drug costs but not hospitalization costs. Costs in all categories decreased after age 65 years. Conclusion Estimates of direct medical costs for patients with RA are substantially higher than cost estimates before the biologic therapy era, and costs are now driven predominantly by the cost of drugs, primarily biologic agents. RA patients with poor function continue to incur substantially higher costs, as do those with comorbid conditions, and sociodemographic characteristics also play an important role in determination of costs. [source]

Phase II study of carboxyamidotriazole in patients with advanced renal cell carcinoma refractory to immunotherapy,,§

CANCER, Issue 11 2005
E489, an Eastern Cooperative Oncology Group study
Abstract BACKGROUND The current study evaluated the response rate and 6-month time to disease progression of the antiangiogenesis agent carboxyamidotriazole (CAI) in patients with metastatic renal cell carcinoma (RCC). METHODS Fifty-seven patients with histologically confirmed metastatic RCC that progressed after biologic therapy (interferon or interleukin-2) were enrolled. Four patients were ineligible. CAI was administered orally as a 28-day cycle. Response and time to disease progression were evaluated. RESULTS Fifteen of 53 eligible patients received > 5 cycles, but 13 patients eventually discontinued treatment because of progressive disease. The majority of toxicities were Grade 1. However, Grade 3/4 toxicities did occur, the majority of which were gastrointestinal in nature. One of 47 patients evaluable achieved a partial response (1.9%) lasting 172 days. Six of 53 patients were alive and disease progression free at 6 months from the start of treatment (11.3%). The median overall survival was 12.5 months. The survival periods in the low-risk, intermediate-risk, and poor-risk groups were 16.2 months, 20.9 months, and 5.8 months, respectively. CONCLUSIONS Patients in trials of second-line therapy appear to have a better prognosis than previously considered, in part because they are eligible for another clinical trial. CAI was found to have little to no effect on the natural history of progressive RCC. Cancer 2005. © 2005 American Cancer Society. [source]

1365: Immunosuppressors and biologic agents

Rationale and timeliness for IL-1,-targeted therapy to reduce allogeneic organ injury at procurement and to diminish risk of rejection after transplantation

CLINICAL TRANSPLANTATION, Issue 3 2010
Alan A. Wanderer
Wanderer AA. Rationale and timeliness for IL-1,-targeted therapy to reduce allogeneic organ injury at procurement and to diminish risk of rejection after transplantation. Clin Transplant 2010: 24: 307,311. © 2010 John Wiley & Sons A/S. Abstract:, Ischemia-reperfusion injury (IRI) involving allograft transplantation and procured organs may in part be induced by stimulation of a newly described innate pro-inflammatory immune system (i.e., NALP-3-inflammasome), which can cause secretion of IL-1, and subsequent neutrophilic inflammation. Ischemia and/or hypoxia/anoxia can induce anaerobic metabolism with metabolic acidosis and subsequent development of danger signals known to stimulate IL-1, secretion from the NALP-3 inflammasome. Observations from IRI studies and hereditary auto-inflammatory syndromes with NALP-3 inflammasome mutations suggest that IL-1, secretion can induce robust neutrophilic inflammation that is responsive to IL-1, targeted therapy. Based on these observations and data from transplantation studies, it may be timely to consider commercially available IL-1, targeted biologic therapy to improve allograft tolerance and viability of procured organs. [source]