RESUMEN
OBJECTIVE: To assess concomitant extra-articular manifestation (EAM) rates in patients with ankylosing spondylitis (AS) treated with anti-tumor necrosis factor (anti-TNF) agents and examine the economic burden of uveitis and inflammatory bowel disease (IBD) in French and German AS patients. METHODS: Previous analyses of uveitis and IBD in AS patients treated with infliximab, etanercept or adalimumab were identified in PubMed/Medline (January 2000 to August 2011). A supplemental analysis incorporated more recent adalimumab clinical trial data (ATLAS [NCT00085644] and RHAPSODY [NCT00478660]). For resource utilization/costs associated with EAMs, the search was expanded to general spondyloarthritis (SpA) conditions (i.e., AS, reactive or psoriatic arthritis, psoriatic spondylitis, IBD and undifferentiated SpA). Direct and indirect yearly costs associated with AS-associated uveitis and IBD were estimated based on interviews with French and German clinicians and literature review. RESULTS: The pooled average rate of anterior uveitis (AU) flares for patients treated with anti-TNF therapy in two meta-analyses and supplemental adalimumab clinical trials was 4.9/100-patient-years (PYs). AU rates (per 100-PYs) were 3.4, 3.7 and 5.7 for infliximab (p=0.26 vs etanercept; p=0.86 vs adalimumab), adalimumab (p=0.033 vs etanercept) and etanercept, respectively. IBD flares (per 100-PYs) were 0.2 for infliximab (p<0.001 vs etanercept; p=0.18 vs adalimumab), 0.63 for adalimumab (p=0.009 vs etanercept) and 2.2 for etanercept. No studies assessing EAM-associated resource utilization or costs in AS patients were found. Direct medical costs associated with IBD treatment ranged from 483 (Germany) to 6443 (France). Clinician-estimated AS-related uveitis direct medical costs were 1410 (Germany) and 1812 (France). CONCLUSIONS: Clinical data synthesis demonstrated significantly lower AU flare rates with adalimumab vs etanercept and significantly lower IBD rates with both adalimumab and infliximab vs etanercept. Economic analysis indicated substantial costs associated with AU and IBD flares secondary to AS in France and Germany. Future economic evaluations of anti-TNF agents should incorporate EAMs and subsequent treatment costs. Limitations include restricted availability of randomized, placebo-controlled clinical trial data, inclusion of data from open-label studies, lack of real-world (i.e., non-trial-based) EAM rates and a lack of EAM-specific direct and indirect costs with which to compare the results presented herein.
Asunto(s)
Antirreumáticos/economía , Antirreumáticos/uso terapéutico , Espondiloartritis/complicaciones , Espondiloartritis/tratamiento farmacológico , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Adalimumab , Anticuerpos Monoclonales/economía , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales Humanizados/economía , Anticuerpos Monoclonales Humanizados/uso terapéutico , Etanercept , Francia , Alemania , Servicios de Salud/economía , Servicios de Salud/estadística & datos numéricos , Humanos , Inmunoglobulina G/economía , Inmunoglobulina G/uso terapéutico , Enfermedades Inflamatorias del Intestino/economía , Enfermedades Inflamatorias del Intestino/etiología , Infliximab , Receptores del Factor de Necrosis Tumoral/uso terapéutico , Estudios Retrospectivos , Espondilitis Anquilosante/complicaciones , Espondilitis Anquilosante/tratamiento farmacológico , Uveítis Anterior/economía , Uveítis Anterior/etiologíaRESUMEN
BACKGROUND: To evaluate the cost-effectiveness of anterior uveitis investigation by Canadian ophthalmologists and to assess the role of implementing national clinical guidelines for such investigation. METHODS: Based on data extracted from the Canadian National Uveitis Survey (CNUS, 2007 version), the cost of investigating a patient with anterior uveitis, according to current practice patterns of Canadian ophthalmologists, was determined and grouped across 4 clinical scenarios: (i) nongranulomatous anterior uveitis in an adult, (ii) granulomatous anterior uveitis in an adult, (iii) granulomatous anterior uveitis with suspected sarcoidosis in an adult or a child, and (iv) nongranulomatous anterior uveitis in a child. Similarly, the cost of investigating a patient with anterior uveitis as per published evidence-based guidelines was determined and compared with the current practice pattern using a cost-minimization model, sensitivity analyses, and Monte Carlo simulations. RESULTS: Ophthalmologists were found to consistently order more tests than recommended by evidence-based guidelines, across each of the scenarios studied (p < 0.05). Overall, complete blood count, erythrocyte sedimentation rate, C-reactive protein, antinuclear antibody, and rheumatoid factor were the most commonly ordered extraneous tests that were not included in the evidence-based guidelines for the routine investigation of anterior uveitis. Also, there were significant differences in the cost of investigating a patient with anterior uveitis when compared with those predicted by adhering to evidence-based clinical practice guidelines. Cost minimization and sensitivity analyses revealed that published guidelines imparted cost savings when compared with current practice patterns across the 4 clinical scenarios studied (p < 0.01). The maximum additional cost was associated with investigating nongranulomatous anterior uveitis in an adult, where a minimal additional cost of $75 per patient was spent. For granulomatous anterior uveitis in an adult, the additional cost was approximately $40, whereas the additional cost for investigating an adult or a child with suspected sarcoidosis was $36. Only $11 of additional cost was spent in the workup of a child with nongranulomatous anterior uveitis. When applied to the Canadian population, adherence to the Clinical Practice Guidelines recommended by the CNUS may result in cost savings of $600,000 per year to the Canadian health care system. INTERPRETATION: Adherence to the evidence-based Clinical Practice Guidelines recommended by the CNUS may result in significant cost savings, with virtually no loss of sensitivity in the routine investigation of anterior uveitis in Canada.