Kivitz 2013.

Methods	Randomized, double‐blind, placebo and active‐controlled trial
Participants	1359 participants, 714 women, 645 men Inclusion: duration of back pain of ≥ 3 months requiring regular use of analgesic medication (> 4 days per week for the past month), including immediate‐release opioids (in which the average daily opioid dose (for a 7‐day period) did not exceed a morphine equivalent dose of 30 mg/d) but excluding acetaminophen, gabapentin or pregabalin as the sole analgesics used for chronic low back pain; primary location of low back pain between the 12th thoracic vertebra and the lower gluteal folds, with or without radiation into the posterior thigh (Quebec Task Force on Spinal Disorders category 1 or 2); average low back pain intensity (LBPI) score of ≥ 4 (on an 11‐point NRS) while receiving current treatment; and Patient’s Global Assessment (PGA) of low back pain of fair, poor or very poor. Exclusion: history of lumbosacral radiculopathy within the past 2 years, vertebral fracture, major trauma or back surgery in the past 6 months; significant cardiac, neurological, or other pain, or psychological conditions; known history of rheumatoid arthritis, seronegative spondyloarthropathy, Paget’s disease of the spine, pelvis or femur, fibromyalgia, tumours or infections of the spinal cord; and any condition that might preclude NSAID use. Patients also were excluded if extended‐release (ER) opioids or long‐acting opioids such as oxycodone controlled release, oxymorphone ER, hydromorphone, transdermal fentanyl or methadone had been used within 3 months of screening
Interventions	NSAID (i): naproxen 1000 mg daily and placebo infusion at baseline, 8 weeks and 16 weeks (N = 295) Reference treatment (ii): placebo tablets daily and placebo infusion at baseline and 8 weeks, 16 weeks (N = 230) Reference treatment (iii): tanezumab 5 mg iv infusion over 5 minutes at baseline and 8 weeks, 16 weeks (N = 232) Reference treatment (iv): tanezumab 10 mg iv infusion over 5 minutes at baseline and 8 weeks, 16 weeks (N = 295) Reference treatment (v): tanezumab 20 mg iv infusion over 5 minutes at baseline and 8 weeks, 16 weeks (N= 295)
Outcomes	Least squares mean difference from baseline on a 11‐point scale: (i versus iii) 0.08 (P = 0.688) Least squares mean difference from baseline on a 11‐point scale: (i versus iv) −0.39 (P = 0.035) Least squares mean difference from baseline on a 11‐point scale: (i versus v) −0.51 (P = 0.006) Adverse events: (i) 142 participants (10 withdrew), (ii) 120 participants (14 withdrew), (iii) 141 participants (11 withdrew), (iv) 171 participants (19 withdrew), (v) 190 participants (28 withdrew)
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Not mentioned
Allocation concealment (selection bias)	Unclear risk	Not mentioned
Blinding (performance bias and detection bias): All outcomes ‐ Patients All outcomes	Low risk	Patients were blinded
Blinding (performance bias and detection bias): All outcomes ‐ Care providers All outcomes	Low risk	Care providers were blinded
Blinding (performance bias and detection bias): All outcomes ‐ Outcome assessors All outcomes	Unclear risk	Not mentioned for all examinations
Incomplete outcome data (attrition bias): All outcomes ‐ Drop‐outs All outcomes	High risk	All trial groups had high drop out rates
Incomplete outcome data (attrition bias): All outcomes ‐ ITT analysis All outcomes	Unclear risk	ITT and per protocol analysis used, unclear which analysis was used in what comparison
Selective reporting (reporting bias)	Low risk	Protocol present
Similarity of baseline characteristics	Low risk	Baseline characteristics were comparable
Co‐interventions avoided or similar	Low risk	Only paracetamol up to 300 mg/day and max 3 days per week was allowed
Compliance acceptable	Unclear risk	Not mentioned
Timing outcome assessments similar	Low risk	Timing was similar