Efficacy and safety of fasinumab in patients with chronic low back pain: a phase II/III randomised clinical trial.

OBJECTIVES: To study the efficacy and safety of fasinumab in moderate-to-severe, chronic low back pain (CLBP). METHODS: In this phase II/III, double-blind, placebo-controlled study, patients with CLBP aged ≥35 years with inadequate pain relief/intolerance to acetaminophen, non-steroidal anti-inflammatory drugs and opioids were randomised to fasinumab 6 or 9 mg subcutaneous every 4 weeks (Q4W), 9 mg intravenous every 8 weeks (Q8W) or placebo. Primary endpoint was change from baseline to week 16 in average daily low back pain intensity (LBPI) numeric rating score. Key secondary efficacy variables included Roland-Morris Disability Questionnaire (RMDQ) and Patient Global Assessment (PGA). The results are based on a modified intent-to-treat analysis of 563/800 planned patients when enrolment was stopped early given emerging signals of joint risk in other osteoarthritis (OA) studies at doses being tested here. RESULTS: Significant placebo-adjusted LBPI reductions at week 16 were observed for fasinumab 9 mg Q4W and Q8W (least squares mean (standard error) -0.7 (0.3); both nominal p<0.05), but not 6 mg (-0.3 (0.3); p=0.39). RMDQ and PGA improvements to week 16 were greatest for fasinumab 9 mg intravenous. Numerically greater efficacy occurred in patients with, versus those without, peripheral OA (pOA) over 16 weeks. Treatment-emergent adverse events (AEs) occurred in 274/418 (65.6%) patients in the combined fasinumab groups and 94/140 (67.1%) placebo patients. Joint AEs, mostly rapid progressive OA type 1, were more frequent in the combined fasinumab groups (19 events in 16 patients (3.8%) vs 1 event in 1 patient (0.7%) for placebo); all except one occurred in pOA patients. CONCLUSIONS: Fasinumab highest doses, but not lower dose, improved both CLBP pain and function. Most joint AEs occurred in pOA patients, consistent with earlier findings in symptomatic OA. Further study is needed of patients with CLBP with and without pOA to determine optimal benefit-risk.

Prospective evaluation of a clinical pathway for suspected appendicitis.

OBJECTIVE: To evaluate the diagnostic accuracy of a clinical pathway for suspected appendicitis combining the Samuel's pediatric appendicitis score (PAS) and selective use of ultrasonography (US) as the primary imaging modality. METHODS: Prospective, observational cohort study conducted at an urban, academic pediatric emergency department. After initial evaluation, patients were determined to be at low (PAS 1-3), intermediate (PAS 4-7), or high (PAS 8-10) risk for appendicitis. Low-risk patients were discharged with telephone follow-up. High-risk patients received immediate surgical consultation. Patients at intermediate risk for appendicitis underwent US. RESULTS: Of the 196 patients enrolled, 65 (33.2%) had appendicitis. An initial PAS of 1-3 was noted in 44 (22.4%), 4-7 in 119 (60.7%), and 8-10 in 33 (16.9%) patients. Ultrasonography was performed in 128 (65.3%) patients, and 48 (37.5%) were positive. An abdominal computed tomography scan was requested by the surgical consultants in 13 (6.6%) patients. The negative appendectomy rate was 3 of 68 (4.4%). Follow-up was established on 190 of 196 (96.9%) patients. Overall diagnostic accuracy of the pathway was 94% (95% confidence interval [CI] 91%-97%) with a sensitivity of 92.3% (95% CI 83.0%-97.5%), specificity of 94.7% (95% CI 89.3%-97.8%), likelihood ratio (+) 17.3 (95% CI 8.4-35.6) and likelihood ratio (-) 0.08 (95% CI 0.04-0.19). CONCLUSIONS: Our protocol demonstrates high sensitivity and specificity for diagnosis of appendicitis in children. Institutions should consider investing in resources that increase the availability of expertise in pediatric US. Standardization of care may decrease radiation exposure associated with use of computed tomography scans.