Annals of Clinical and Experimental NeurologyAnnals of Clinical and Experimental NeurologyАнналы клинической и экспериментальной неврологии2075-54732409-2533Eco-Vector102710.17816/ACEN.1027ReviewsОбзорыReview ArticleMonoclonal antibodies as analgesia of chronic low back pain: a systematic review and meta-analysis of efficacy and safetyПрименение моноклональных антител в качестве анальгетиков при хроническом болевом синдроме в нижней части спины: систематический обзор и метаанализ эффективности и безопасностиhttps://orcid.org/0009-0002-2197-064XBudiputraNobelБудипутраНобел
Indonesia

MD, Universitas Pelita Harapan

доктор медицины, Университет Пелита Харапан

nobelbudiputra@gmail.comhttps://orcid.org/0000-0002-2129-842XBudiputriCharista LydiaБудипутриХариста Лидиа
Indonesia

MD, Universitas Pelita Harapan

доктор медицины, Университет Пелита Харапан

charistalydia@gmail.comhttps://orcid.org/0000-0002-7764-4686MuljonoMichelle PatriciaМулджоноМишель Патрисиа
Indonesia

MD, Universitas Pelita Harapan

доктор медицины, Университет Пелита Харапан

mulyonomichelle12@gmail.comUniversitas Pelita HarapanУниверситет Пелита Харапан0807202418270833008202320102023Copyright ©; 2024, Budiputra N., Budiputri C., Muljono M.Copyright ©; 2024, Будипутра Н., Будипутри Х., Мулджоно М.2024Budiputra N., Budiputri C., Muljono M.Будипутра Н., Будипутри Х., Мулджоно М.https://creativecommons.org/licenses/by/4.0https://annaly-nevrologii.com/pathID/article/view/1027

Introduction. Monoclonal antibodies (mAb) emerged as a possible option in addressing the partial response to current treatment modalities in chronic low back pain (CLBP).

Objective: to evaluate the efficacy and safety of mAb for CLBP.

Materials and Methods. Randomized controlled trials on adult patients with CLBP who received mAb-therapy compared to those who did not as a control group. The result was the changes in Low Back Pain Intensity (LBPI) Numeric Rating Score and Roland–Morris Disability Questionnaire (RMDQ) indicating improved pain, disability, and the risk of adverse events. Meta-analysis, risk of bias, and confidence in the evidence for each analysis were assessed. We aimed at reviewing current treatment methods for degenerative lumbosacral spinal stenosis with an emphasis on surgical treatment methods.

Results. Six studies were included, with a total of 3851 participants. mAb significantly reduce LBPI and RMDQ score (weighted mean difference –1.48; 95% CI –2.63 to –0.33; p = 0.01). Tanezumab and fasinumab were significantly reduced both LBPI (weighted mean difference of –4.11; 95% CI –6.27 to –1.95; p = 0.0002 and weighted mean difference –0.24; 95% CI –0.47 to –0.02; p = 0.04 respectively) and RMDQ scores (weighted mean difference –3.72; 95% –5.48 to –1.97 and weighted mean difference –0.50; 95% –0.73 to –0.26 respectively, both p < 0.0001). The mAb have significantly greater odds of any adverse events (OR 1.23; 95% 1.06 to 1.43; p = 0.007) but no greater odds regarding serious adverse events (OR 1.00; 95% 0.69 to 1.46; p = 0.98).

Conclusion. Depending on the types of drugs used, mAb had a favorable outcome and were relatively safe in reducing LBPI and RMDQ scores.

Введение. Моноклональные антитела (мАТ) всё чаще рассматриваются как возможное средство для достижения частичного ответа при хроническом болевом синдроме (ХБС) в нижней части спины.

Цель: изучить эффективность и безопасность мАТ при ХБС в нижней части спины.

Материалы и методы. Проведены рандомизированные контролируемые исследования с участием взрослых пациентов, страдающих ХБС в нижней части спины и получавших мАТ, и контрольной группы, не получавшей мАТ. Выявляли изменение оценки по числовой оценочной шкале выраженности боли в нижней части спины (LBPI) и опроснику Роланда–Морриса для определения уровня инвалидизации (RMDQ), отражающие уменьшение боли, сопутствующей инвалидизации, а также риск нежелательных явлений. Нами подготовлен метаанализ и проанализированы риск систематических ошибок и доказательная сила каждого отдельного анализа.

Результаты. В обзор вошли 6 исследований, в которых участвовал в общей сложности 3851 пациент. Применение мАТ привело к значимому снижению оценки по LBPI и RMDQ: средневзвешенная разница –1,48; 95% доверительный интервал (ДИ) (–2,63; –0,33), p = 0,01. На фоне применения танезумаба и фасинумаба отмечалось значимое снижение балла по LBPI (танезумаб — средневзвешенная разница –4,11; 95% ДИ (–6,27)–(–1,95), p = 0,0002; фасинумаб — средневзвешенная разница –0,24; 95% ДИ (–0,47)–(–0,02); p = 0,04) и RMDQ (танезумаб — средневзвешенная разница –3,72; 95% ДИ (–5,48)–(–1,97); p < 0,0001; фасинумаб — средневзвешенная разница –0,50; 95% ДИ (–0,73)–(–0,26); p < 0,0001). На фоне применения мАТ значимо увеличивался риск развития любых нежелательных явлений (отношение шансов 1,23; 95% ДИ 1,06–1,43; p = 0,007), однако риск развития серьёзных нежелательных явлений не повышался (отношение шансов 1,00; 95% ДИ 0,69–1,46; p = 0,98).

Заключение. В зависимости от препарата применение мАТ приводило к благоприятному исходу с уменьшением оценки по LBPI и RMDQ и было относительно безопасным.

monoclonal antibodytanezumabfasinumabfulranumabdenosumabchronic low back painLBPIRMDQмоноклональное антителотанезумабфасинумабфулранумабденосумабхроническая боль в нижней части спиныLBPIRMDQCoombs D.M., Machado G.C., Richards B. et al. Healthcare costs due to low back pain in the emergency department and inpatient setting in Sydney, Australia. Lancet Reg. Health West Pac. 2021;7:100089. DOI: 10.1016/j.lanwpc.2020.100089Menezes Costa L. da C., Maher C.G., Hancock M.J. et al. The prognosis of acute and persistent low-back pain: a meta-analysis. Can. Med. Assoc. J. 2012;184:E613–E624. DOI: 10.1503/cmaj.111271Bannwarth B., Kostine M. Targeting nerve growth factor (NGF) for pain management: what does the future hold for NGF antagonists? Drugs. 2014;74:619–626. DOI: 10.1007/s40265-014-0208-6Sánchez-Robles E.M., Girón R., Paniagua N. et al. Monoclonal antibodies for chronic pain treatment: present and future. Int. J. Mol. Sci. 2021;22:10325. DOI: 10.3390/ijms221910325Keizer R.J., Huitema A.D.R., Schellens J.H.M, Beijnen J.H. Clinical Pharmacokinetics of therapeutic monoclonal antibodies. Clin. Pharmacokinet. 2010;49:493–507. DOI: 10.2165/11531280-000000000-00000Dimitroulas T., Lambe T., Raphael J.H. et al. Biologic drugs as analgesics for the management of low back pain and sciatica. Pain Med. 2019;20(9):1678–1686. DOI: 10.1093/pm/pny214Page M.J., McKenzie J.E., Bossuyt P.M. et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372:n71. DOI: 10.1136/bmj.n71Nair A. Quality of a randomized-controlled trial- how to assess and improve reporting? Saudi J. Anaesth. 2022;16:257. DOI: 10.4103/sja.sja_870_21Guyatt G.H., Oxman A.D., Vist G.E. et al. GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ. 2008;336(7650):924–926. DOI: 10.1136/bmj.39489.470347.ADCai G., Laslett L.L., Aitken D. et al. Effect of zoledronic acid and denosumab in patients with low back pain and modic change: a proof-of-principle trial. J. Bone Miner. Res. 2018;33(5):773–782. DOI: 10.1002/jbmr.3376Kivitz A.J., Gimbel J.S., Bramson C. et al. Efficacy and safety of tanezumab versus naproxen in the treatment of chronic low back pain. Pain. 2013;154(7):1009–1021. DOI: 10.1016/j.pain.2013.03.006Dakin P., Kivitz A.J., Gimbel J.S. et al. Efficacy and safety of fasinumab in patients with chronic low back pain: a phase II/III randomised clinical trial. Ann. Rheum. Dis. 2021;80(4):509–517. DOI: 10.1136/annrheumdis-2020-217259Sanga P., Polverejan E., Wang S. et al. Efficacy, safety, and tolerability of fulranumab as an adjunctive therapy in patients with inadequately controlled, moderate-to-severe chronic low back pain: a randomized, double-blind, placebo-controlled, dose-ranging, dose-loading phase II study. Clin. Ther. 2016;38(6):1435–1450. DOI: 10.1016/j.clinthera.2016.03.030Brown M.T., Murphy F.T., Radin D.M. et al. Tanezumab reduces osteoarthritic hip pain: results of a randomized, double‐blind, placebo‐controlled phase III trial. Arthritis Rheum. 2013;65:1795–1803. DOI: 10.1002/art.37950Bramson C., Herrmann D.N., Carey W. et al. Exploring the role of tanezumab as a novel treatment for the relief of neuropathic pain. Pain Med. 2015;16(6):1163–1176. DOI: 10.1111/pme.12677Dakin P., DiMartino S.J., Gao H. et al. The efficacy, tolerability, and joint safety of fasinumab in osteoarthritis pain: a phase IIb/III double‐blind, placebo‐controlled, randomized clinical trial. Arthritis Rheumatol. 2019;71(11):1824–1834. DOI: 10.1002/art.41012Mayorga A.J., Wang S., Kelly K.M., Thipphawong J. Efficacy and safety of fulranumab as monotherapy in patients with moderate to severe, chronic knee pain of primary osteoarthritis: a randomised, placebo- and active-controlled trial. Int. J. Clin. Pract. 2016;70(6):493–505. DOI: 10.1111/ijcp.12807Sanga P., Katz N., Polverejan E. et al. Long‐term safety and efficacy of fulranumab in patients with moderate‐to‐severe osteoarthritis pain: a phase II randomized, double‐blind, placebo‐controlled extension study. Arthritis Rheumatol. 2017;69(4):763–773. DOI: 10.1002/art.39943Jones T.D., Carter P.J., Plückthun A. et al. The INNs and outs of antibody nonproprietary names. MAbs. 2016;8(1):1–9. DOI: 10.1080/19420862.2015.1114320Bayer V. An overview of monoclonal antibodies. Semin. Oncol. Nurs. 2019;35(5):150927. DOI: 10.1016/j.soncn.2019.08.006Watson J.J., Allen S.J., Dawbarn D. Targeting nerve growth factor in pain. BioDrugs. 2008;22(6):349–359. DOI: 10.2165/0063030-200822060-00002McKelvey L., Shorten G.D., O’Keeffe G.W. Nerve growth factor-mediated regulation of pain signalling and proposed new intervention strategies in clinical pain management. J. Neurochem. 2013;124(3):276–289. DOI: 10.1111/jnc.12093Gjefsen E., Bråten L.C.H, Goll G.L. et al. The effect of infliximab in patients with chronic low back pain and Modic changes (the BackToBasic study): study protocol of a randomized, double blind, placebo-controlled, multicenter trial. BMC Musculoskelet. Disord. 2020;21(1):698. DOI: 10.1186/s12891-020-03720-5Moretti A., de Sire A., Curci C. et al. Effectiveness of denosumab on back pain- related disability and quality-of-life in patients with vertebral fragility fractures. Curr. Med. Res. Opin. 2019;35(1):151–155. DOI: 10.1080/03007995.2018.1545636Miller P.D., Pannacciulli N., Malouf-Sierra J. et al. Efficacy and safety of denosumab vs. bisphosphonates in postmenopausal women previously treated with oral bisphosphonates. Osteoporosis Int. 2020;31(1):181–191. DOI: 10.1007/s00198-019-05233-xCummings S.R., Martin J.S., McClung M.R. et al. Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N. Engl. J. Med. 2009;361(8):756–765. DOI: 10.1056/NEJMoa0809493Oeckinghaus A., Ghosh S. The NF-κB family of transcription factors and its regulation. Cold Spring Harb. Perspect. Biol. 2009;1(4):a000034–a000034. DOI: 10.1101/cshperspect.a000034Markman J.D., Bolash R.B., McAlindon T.E. et al. Tanezumab for chronic low back pain: a randomized, double-blind, placebo- and active-controlled, phase 3 study of efficacy and safety. Pain. 2020;161(9):2068–2078. DOI: 10.1097/j.pain.0000000000001928Katz N., Borenstein D.G., Birbara C. et al. Efficacy and safety of tanezumab in the treatment of chronic low back pain. Pain. 2011;152(10):2248–2258. DOI: 10.1016/j.pain.2011.05.003