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McLeod, S. (2013).
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ProEdTN. (2013).
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Hutfless, S., Lau, B. D., Wilson, L. M., Lazarev, M., & Bass, E. B. (2014).
Abstract: The clinical management of Crohn's disease is complicated. Practice guidelines for Crohn's disease recommend that clinicians take into account the disease location, severity, complications, and extra-intestinal manifestations when choosing a treatment strategy. However, no universal treatment strategy exists. The lack of consensus about the best treatment strategy can result in confusion and frustration for the Crohn's disease patient as well as practitioners who treat Crohn's disease patients. Medications are the preferred treatment for Crohn's disease with surgical interventions reserved for complications of disease or evidence of dysplasia. Medical therapy in Crohn's disease targets intestinal inflammation with the intent of altering the natural history of the disease. Corticosteroids and aminosalicylates such as sulfasalazine have been used since the 1950s. Immunomodulators (6-mercaptopurine, azathioprine, and methotrexate) have been used for the treatment of Crohn's disease since the 1970s, although use of these medications was not routine until the 1990s. The first biologic tumor necrosis factor (TNF)-alpha inhibitor, infliximab, was approved by the Food and Drug Administration (FDA) for the treatment of Crohn's disease in adults in 1998. The FDA-approved monoclonal antibodies against TNF-alpha inhibitor also include adalimumab and certolizumab pegol. Another biologic agents used for the treatment of Crohn's disease include natalizumab, a monoclonal antibody against cellular adhesion molecule alpha4-integrin that is FDA-approved for Crohn's disease in adults. Our recent systematic review addressed several Key Questions in the management of Crohn's disease. In that review, we identified several important gaps in the evidence. We used the population, intervention, comparison, outcome, timing, setting (PICOTS) framework to identify gaps from the evidence in relationship to the populations, interventions, comparisons, outcomes, timing, and settings relevant to treatments for Crohn's disease. Several gaps related to the target population (children, non-white, and risk stratification based on patient characteristics). Other gaps related to interventions and comparisons of interest (step up versus top down treatment and head to head comparisons within and between treatment classes), outcomes of interest (mucosal healing, and patient-reported symptoms), or a timing issue (remission beyond 2 years). The objective of this report is to identify and prioritize existing gaps in the synthesized literature pertaining to pharmacological induction and maintenance of remission for patients with Crohn's disease by engaging stakeholders using a modified Delphi method.
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Hutfless, S., Almashat, S., Berger, Z., Wilson, L. M., Bonson, E., Chen, Q., et al. (2014).
Abstract: The purpose of this review was to compare the efficacy and safety of biologics, immunomodulators, corticosteroids, and aminosalicylates in the treatment of Crohn's disease. We searched MEDLINE(R) (1966 through June 2011), Embase(R) (1974 through June 2011), and the Cochrane Central Register of Controlled Trials (Issue 2, 2011). Two reviewers independently reviewed titles, abstracts, and articles, and included English-language articles that reported on induction or maintenance of remission in placebo-controlled or head-to-head randomized controlled trials. We also included observational studies with a comparison group if they reported on the safety of treatment. Two reviewers extracted study information using standardized forms and independently assessed study quality. Efficacy was measured by induction and maintenance of remission. Remission was defined using the Crohn's Disease Activity Index, mucosal healing, the absence of Crohn's disease hospitalizations or surgeries, reduction of steroids, fistula healing, and patient-reported outcomes. A difference of 10 percentage points in the outcome between treatment groups was considered clinically meaningful. The safety outcomes of interest were mortality, occurrence of lymphomas and other cancers, infections, infusion- and injection-site reactions, and bone fractures for adults and children. Growth was an additional safety concern for children. We included 136 studies involving 148,733 patients. Twenty-three percent of trials directly compared different treatment strategies. The majority of trials excluded patients with mild disease and those with a history of surgical resection. The majority of trials allowed patients to take other Crohn's disease treatments during the trial. For adults, infliximab and 6-methyl-prednisolone were consistently favored over placebo across the induction and maintenance outcomes. Natalizumab and azathioprine were favored over placebo across the maintenance outcomes. Other comparisons either did not have more than one outcome reported or had inconsistent results. The quality of the safety evidence was poor due to poor reporting of the methods in trials and poor confounding control in observational studies, and no strong signals of harm were identified. For children, the strength of evidence was low or insufficient to support the efficacy of any medication to induce or maintain remission. No pediatric study reported on serious adverse events such as mortality, lymphoma, or other cancers. Measuring the efficacy of medications using multiple outcomes, infliximab and 6-methyl-prednisolone induce and maintain remission in adults with Crohn's disease. Natalizumab and azathioprine maintain remission. Comparing Crohn's disease medications directly using pragmatic clinical trials will help to understand the effectiveness of medications in clinical practice using outcomes other than the Crohn's Disease Activity Index.
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Lee, S., Coleman, C. I., Limone, B., Kaur, R., White, C. M., Kluger, J., et al. (2012).
Abstract: To examine the comparative effectiveness of biologic systemic agents versus nonbiologic systemic agents or phototherapy, on an individual drug level, for treatment of chronic plaque psoriasis (CPP) and to determine patient and disease characteristics that modify outcomes of interest. Medline, the Cochrane Central Register of Controlled Trials, and Web of Science from inception to June 2012, with no language restrictions. Randomized controlled trials (RCTs) and observational studies were included in our review if they compared treatment with Food and Drug Administration-approved biologic systemic agents with either an approved nonbiologic systemic agent or phototherapy in adult patients with CPP and provided data on at least one prespecified outcome. Using predefined criteria, data on study design and population, interventions, quality, and outcomes were extracted. No quantitative analyses were performed and all data were qualitatively synthesized. The strength of evidence (SOE) for individual outcome was rated, when possible, as insufficient (I), low (L), moderate (M), or high (H). The applicability of the body of evidence was described. Five RCTs and four observational studies directly compared therapies from the specified classes. An additional five studies provided data on the transition of patients from one therapy to another. Studies generally reported short-term outcomes (median of 24 weeks) in small (<200 subjects) international patient populations. Compared with methotrexate, adalimumab improved health-related quality of life (HRQoL) [SOE: L], Psoriasis Area and Severity Index (PASI) [SOE: L], Physician's Global Assessment (PGA) score [SOE: L], and patient's assessment of disease severity score [SOE: L], while reducing pain [SOE: L] and pruritus [SOE: L] with no effect on infection rates [SOE: L]. Compared with acitretin, etanercept improved PASI [SOE: M] and compared with methotrexate, infliximab improved HRQoL [SOE: L], PASI [SOE: L], and PGA [SOE: L]. Compared with methotrexate, ustekinumab improved PGA [SOE:L]. Data were insufficient for any other comparisons and outcomes. Data from the post-hoc subgroup analysis of one RCT that compared treatment with adalimumab with treatment with methotrexate suggested that as disease severity improved, so did a patient's HRQoL. Data were insufficient to evaluate the impact of any other patient or disease characteristics on outcomes. In patients with CPP, there were limited data directly comparing systemic biologic agents with either systemic nonbiolgic agents or with phototherapy on an individual drug level. Overall there is insufficient evidence to determine the comparative effectiveness of individual therapies, as compared with each other between the specified classes, with few exceptions. For the comparisons of adalimumab versus methotrexate, infliximab versus methotrexate, ustekinumab versus methotrexate, and etanercept versus acitretin, there is predominantly low strength of evidence favoring the individual biologic agent versus the nonbiologic agent. Additional trials directly comparing biologic systemic agents, systemic nonbiologic agents, and phototherapy are needed.
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