Efficacy and safety of combination therapy with 5% lidocaine medicated plaster and pregabalin in post-herpetic neuralgia and diabetic polyneuropathy

ABSTRACT

Objective: Neuropathic pain is often difficult to treat due to a complex pathophysiology. This study evaluated the efficacy, tolerability and safety of combination therapy with 5% lidocaine medicated plaster and pregabalin for neuropathic pain in patients with post-herpetic neuralgia (PHN) or painful diabetic polyneuropathy (DPN).

Methods: Patients completing 4-week monotherapy with 5% lidocaine medicated plaster or pregabalin were enrolled in an 8-week combination phase. Patients with adequate response to monotherapy (recalled average pain intensity of 4 or less on 11-point numeric rating scale in the previous 3 days [NRS-3 score]) continued their previous therapy, whereas those with insufficient response received combination therapy. Efficacy endpoints included change in NRS-3 from combination phase baseline, Patient and Clinical Global Impression of Change (PGIC/CGIC), and patient's satisfaction with treatment. Safety evaluation included adverse events (AEs), drug-related AEs (DRAEs), and withdrawal due to AEs.

Clinical trial registration: EudraCT No. 2006-003132-29.

Results: Of 229 patients in the per-protocol set (PPS: 68 PHN and 161 DPN), 71 received 5% lidocaine medicated plaster monotherapy, 57 had pregabalin added to 5% lidocaine medicated plaster, 57 pregabalin monotherapy and 44 received 5% lidocaine medicated plaster in addition to continued pregabalin treatment. There were no meaningful differences in demographic data between the treatment groups. Patients continuing on monotherapy demonstrated additional decreases in NRS-3 scores. Patients receiving combination therapy achieved clinically relevant reduction in NRS-3 values in addition to improvement achieved during the 4 weeks of monotherapy. Improvement was similar between the two combination therapy groups. Considerable improvements in patients’ treatment satisfaction were reported. Incidences of AEs were in line with previous reports for the two treatments and combination therapy was generally well tolerated.

Conclusions: In patients with PHN and painful DPN failing to respond to monotherapy, combination therapy with 5% lidocaine medicated plaster and pregabalin provides additional clinically relevant pain relief and is safe and well-tolerated.

Key words: :

• Diabetic polyneuropathy
• Lidocaine plaster
• Neuropathic pain
• Post-herpetic neuralgia
• Pregabalin

Transparency

Declaration of funding

Grünenthal GmbH sponsored this study and provided funding for editorial assistance in the preparation of this manuscript. No honorarium was paid to the authors for the preparation of this article. The authors retain sole responsibility for the views expressed in this article, which may or may not be shared by the sponsors.

Declaration of financial/other relationships

R.B. has disclosed that he has received honoraria from Allergan, Schwarz, Pfizer, Grünenthal, Medtronic, Mundipharma, Eisai, Sanofi-Pasteur and Genzyme and received research funding from Pfizer, Grünenthal and Genzyme. A.B. has disclosed he has received honoraria from Allergan, Schwarz, Pfizer and Grünenthal. V.M. has disclosed that he has received honoraria from Grünenthal. G.L. has disclosed no relevant financial relationships. I.S. has disclosed she is an employee of Grünenthal. M.G.S. has disclosed he has received honoraria from Grünenthal and that his institution received remuneration to cover costs of patient visits and recruitment during the study.

All peer reviewers receive honoraria from CMRO for their review work. Peer Reviewer 1 and Peer Reviewer 2 have disclosed they have no relevant financial relationships.

Acknowledgements

Medical writing assistance was provided by Fiona Murray-Zmijewski of Wolters Kluwer Health and was funded by Grünenthal GmbH.

The authors would like to thank the following study investigators: Prof. Dr G. Nell, Dr M. De Meulemeester, Dr H. Radovan, Dr M. Petr, Dr V. Stanislav, Dr V. Dana, Dr Z. Šolle, O. Vyšata, Dr B. Steinberg, Minnich J., Dr M. Sanuri, Prof. Dr D. Ziegler, Dr B. Bergtholdt, Laus S., Lehmann R., Dr H.-D. Stahl, Dr S. Mindt-Prüfert, Dr T. Meier, Dr J. Ignacio Calvo, Dr R. Gálvez, Dr L. Miguel Torres, Dr E. Catalá, Dr J. Guitart, Dr M. Blagden, Dr B. Silvert, Dr D. Haworth, Dr S. Ratcliffe, Dr P. D. Rogers, Dr M. Fingler, Dr I. Adanic-Mikloska, Dr A. Barada, Dr M. Persoli, Dr D. Spisic, Dr C. Power, Dr G. Lauria, Dr R. Casale, E. Motta, K. Boczar, M. Koziol, A. Szczepańska-Szerej, J. Pyszkowska, D. Szewczyk-Urgacz, Dr M. Miguel Rosa, Dr R. Duarte, Prof. I. Demidova, Prof I. Gurieva, G. Požlep, A. Pražnikar, N. Krčevski-Škvarč.