Table 2.
Biological treatments under clinical development to treat discogenic LBP
| Therapeutics | Authors | Year | Number of patients | Study design | Treatment | Analysis variables | Follow-up period | Outcomes |
|---|---|---|---|---|---|---|---|---|
| PRP | Akeda et al.183 | 2011 | 6 | Prospective single arm | Intradiscal injection of 1.5 mL of PRP | VAS, RDQ, MRI (T2) | 6 M | VAS and RDQ were decreased at 1 month and sustained for 6 months. No change in T2 values was observed. |
| PRP | Tuakli-Wosornu et al.186 | 2016 | 47 | Prospective double-blind RCT | Intradiscal injection of 1–2 mL of PRP (n = 29) vs. contrast agent (n = 18) | FRI, NRS, 36-item Short Form Health Survey, and modified NASS Outcome Questionnaire | 12 M | The improvement of patients’ LBP symptoms and function occurred as early as 8 weeks after treatment and was maintained for at least 1 year. |
| PRP | Levi et al.185 | 2016 | 22 | Single arm | Intradiscal injection of 1.5 mL of PRP at one or more levels | VAS, ODI | 6 M | 14%, 32%, and 47% of the patients achieved a successful outcome at 1, 2, and 6 months, while the percentages reaching a 50% decrease in VAS were 36%, 41%, and 47%. |
| PRP | Lutz187 | 2017 | 1 | Case report | Intradiscal injection of 1.5 mL of PRP | Pain, range of motion, MRI (T2) | 12 M | Improvements in pain and range of motion and increased T2 nuclear signal intensity were observed. |
| PRP | Akeda et al.184 | 2017 | 14 | Prospective single arm | Intradiscal injection of 2 mL of PRP | VAS, RDQ, X-ray, MRI (T2) | 12 M |
The mean pain scores before treatment (VAS: 7.5 ± 1.3; RDQ: 12.6 ± 4.1) were decreased at 1 month and were sustained at 6 months (VAS, 3.2 ± 2.4, RDQ; 3.6 ± 4.5) and 12 months (VAS, 2.9 ± 2.8; RDQ, 2.8 ± 3.9) after treatment. No significant changes in the mean T2 values was observed. |
| TNF-α inhibitors | Karppinen et al.178 | 2003 | 72 | Open-label, controlled study to treat sciatica | Infliximab (3 mg, n = 10) vs. saline (n = 62) | VAS, ODQ, MRI (T2 and T1), SLR, Schober | 3 M | The infliximab group had more pain reduction than the control group (painless patients after 2 weeks: 60% vs. 16%; after 3 months: 90% vs. 46%). At 1 month, all patients in the infliximab group went back to work, while 38% in the control group remained on sick leave. |
| TNF-α inhibitors | Cohen et al.179 | 2009 | 24 | Double-blind, controlled, multidose | Epidural etanercept (n = 18) vs. placebo (n = 6) | NRS, ODI, global perceived effect | 1 M | Improvements in leg and back pain were reported in the treated group after 1 month. One patient in the saline group (17%), six patients in the 2 mg group (100%), and four patients each in the 4 mg and 6 mg groups (67%) reported >50% reduction in leg pain and a positive global perceived effect 1 month after treatment, which persisted to 6 months after treatment. |
| TNF-α inhibitors | – | 2018 | 126 | RCT double blind, multicenter | Infliximab vs. placebo | ODI, NRS, STIR, RDQ | 9 M | Recruiting (Clinical trial ID: NCT03704363) |
| NGF inhibitors | Katz et al.189 | 2011 | 217 | RCT double-blind, multicenter, parallel | Tanezumab (n = 88), naproxen (n = 88) or placebo (n = 41) | aLBPI, RDQ, BPI-SF, PGA, Patients’ Global Evaluation, rescue medication use | 6 W | The tanezumab group had a better reduction in aLBPI, RDQ and other secondary outcomes, except rescue medication use, than the naproxen or placebo group. |
| NGF inhibitors | Kivitz et al.190 | 2013 | 1 347 | RCT, double-blind, multicenter, parallel phase IIB | Tanezumab (5, 10, or 20 mg), naproxen (500 mg), or placebo | aLBPI, RDQ, PGA | 16 W |
Tanezumab at 10 and 20 mg had a similar efficacy in improving aLBPI, RDQ, and the PGA scores vs. both placebo and naproxen. Tanezumab at 5 mg improved the PGA scores vs. placebo. Arthralgia, pain in extremity, headache, and paresthesia were the most commonly reported AEs by tanezumab. |
| NGF inhibitors | Gimbel et al.191 | 2014 | 848 | Noncontrolled, randomized, multicenter | Tanezumab at 10 mg (n = 321) vs. 20 mg (n = 527) | BPI-SF, RDQ, PGA | 200 d | Both tanezumab at 10 mg and 20 mg provided sustained effectiveness. Tanezumab at 10 mg had better tolerability. |
| NGF inhibitors | Hochberg et al.192 | 2016 | 1 564 | Blinded adjudication of previous reports | Tanezumab | – | ~200 d | Tanezumab treatment was not associated with an increase in osteonecrosis but was associated with an increase in rapid progression of osteonecrosis. |
NRS numeric rating scale, VAS visual analog scale, ODI Oswestry disability index, RDQ Roland-Morris disability questionnaire, FRI functional rating index, RCT randomized controlled trial, aLBPI average LBP intensity, STIR short tau inversion recovery, PGA patient’s global assessment, AEs adverse events, NASS North American Spine Society, SLR straight-leg-raising test, BPI-SF brief pain inventory-short form