ABSTRACT
Background/Aims@#PF-00547659 is a monoclonal antibody against human mucosal addressin cell adhesion molecule-1 (MAdCAM-1) that prevents the binding of α4β7+ lymphocytes to MAdCAM-expressing sites in the gastrointestinal tract with high affinity and selectivity, and is being developed for the treatment of Crohn’s disease (CD). @*Methods@#OPERA is a randomized, multicenter, double-blind, placebo-controlled study to investigate the efficacy, safety, and pharmacokinetics of PF-00547659 following subcutaneous administration in subjects with active CD, a history of failure or intolerance to anti-tumor necrosis factor and/or immunosuppressants, high-sensitivity C-reactive protein > 3.0 mg/L, and ulcers on colonoscopy. The primary endpoint was Crohn’s Disease Activity Index-70 response at week 8 or 12. Subpopulation analyses for Asian subjects were performed as some differences are observed in genetics and clinical phenotypes in Asian CD patients compared with Western patients. @*Results@#In this study, 265 CD subjects were randomized, with a subpopulation of 21 subjects (8 Japanese and 13 Korean) defined as the Asian population. In the overall and Asian populations; PF-00547659 was pharmacologically active as evidenced by soluble MAdCAM and circulating β7+ central memory CD4+ T-lymphocytes, although no clear evidence of efficacy was observed in any clinical endpoints; pharmacokinetics of PF-00547659 in the Asian subpopulation was generally comparable to the overall population; and the safety profile of PF-00547659 appeared acceptable up to 12 weeks of treatment. @*Conclusions@#In the overall and Asian populations, efficacy of PF-00547659 could not be demonstrated using any clinical endpoints compared with placebo. Pharmacokinetics and safety of PF-00547659 were generally comparable. Further studies with larger numbers of patients are required to confirm our results. (Trial Registration Number: NCT01276509)
ABSTRACT
Low Back Pain (LBP) is one of the main causes of disability in the whole world. In most cases, its presentation is considered benign and usually managed quite easily. However, in a low percentage of cases LBP is secondary to a serious pathology. Patients with Multiple Sclerosis (MS), for instance, are often affected also by LBP, and LBP could also be an initial symptom of MS. Moreover, patients with MS can present with a w ide range of clinical symptoms, as the Restless Legs Syndrome – RLS. In these specific cases, the ability to recognize a serious pathology is a key component of the physical therapist practice. Both conditions, nonspecific LBP and RLS, have been found in a patient that was referred with diagnosis of bilateral sciatica.