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Dissecting the inflammatory response in polymyalgia rheumatica: the relative role of IL-6 and its inhibition

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Abstract

The efficacy of tocilizumab (TCZ), a monoclonal antibody to the interleukin (IL)-6 receptor, in suppressing disease activity in glucocorticoid-naïve patients with new-onset polymyalgia rheumatica (PMR) was studied. Its effect on a panel of cytokines and growth factors was evaluated. Three patients, fulfilling the PMR ACR/EULAR criteria, received TCZ at the dosage of 8 mg/kg every 4 weeks for three times followed by prednisone 0.2 mg/kg in case of inefficacy. Concentrations of IL-10, IL-6, tumour necrosis factor (TNF)-α, IL-1β, IL-10, IL-17, interferon (IFN)-γ, vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), and leukaemia inhibitory factor (LIF) were measured at baseline, after 72 h of the first TCZ infusion and then at weeks 1, 4, 5, 8, 9, 12, 13, 14, 16, and 22. A slight clinical improvement was seen only after the first TCZ infusion, but was largely inferior to that of conventional doses of GC administered subsequently. An ischaemic visual accident suggestive of GCA occurred in one patient during TCZ treatment. IL-6 was increased at baseline compared to controls, further increased after the first TCZ infusion, and was suppressed by GC. IL-17 production decreased during TCZ treatment and reverted to pre-treatment levels after GC. VEGF e PDGF showed a less constant pattern, but an increase of VEGF concentration antedated visual symptoms. The other cytokines were not detectable in patients and controls. In our small sample, TCZ was not able to suppress inflammation at the same degree as GC. As a result, monotherapy with TCZ in PMR cannot be recommended, although its efficacy as adjunctive treatment in GC-resistant patients should be further evaluated.

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Author information

Author notes

  1. Dario Camellino and Stefano Soldano contributed equally to this work.

Authors and Affiliations

  1. Autoimmunology Laboratory, Department of Internal Medicine, University of Genoa, Genoa, Italy

    Dario Camellino

  2. Research Laboratory and Academic Division of Clinical Rheumatology, Department of Internal Medicine, University of Genoa, Viale Benedetto XV, 6, 16131, Genoa, Italy

    Stefano Soldano, Maurizio Cutolo & Marco A. Cimmino

Authors
  1. Dario Camellino
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  2. Stefano Soldano
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  3. Maurizio Cutolo
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  4. Marco A. Cimmino
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Contributions

All authors designed together the study and substantially participated in its execution. In particular, DC, SS, MM, and MAC designed the study, DC evaluated patients and collected blood samples, SS handled and analysed blood samples, and DC, MAC, and SS managed the data, discussed and interpreted the results, and wrote the manuscript. All authors had full access to the study data. DC and SS share the first authorship.

Corresponding author

Correspondence to Marco A. Cimmino.

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Conflict of interest

The authors declare no conflict of interests. DC and MAC participated in the GiACTA study sponsored by Roche, without receiving personal fees.

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Camellino, D., Soldano, S., Cutolo, M. et al. Dissecting the inflammatory response in polymyalgia rheumatica: the relative role of IL-6 and its inhibition. Rheumatol Int 38, 1699–1704 (2018). https://doi.org/10.1007/s00296-018-4086-1

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  • DOI: https://doi.org/10.1007/s00296-018-4086-1

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