Tocilizumab for the treatment of adult-onset Still’s disease

ABSTRACT

Introduction: Adult-onset Still´s disease (AOSD) is a systemic inflammatory condition that affects mainly young people. The clinical course consists of two distinctive patterns: one with a predominance of systemic symptoms and another manifested by progressive chronic polyarthritis. Glucocorticoids remain the mainstay in the treatment of AOSD. However, biologic therapies are often required to achieve clinical remission and allow glucocorticoid discontinuation.

Areas covered: The review summarizes the main retrospective and prospective studies, and case series on the use of the anti-interleukin (IL)-6 receptor tocilizumab in AOSD.

Expert opinion: Since IL-6 serum levels are highly increased in both active systemic and polyarticular phenotypes, IL-6 blockade was considered to be a plausible therapeutic option for the management of AOSD. Tocilizumab, the only anti-IL-6-receptor antagonist currently available for AOSD, has proved to be effective for the management of refractory AOSD patients, including those with life-threatening complications. Nevertheless, there are some reports describing patients who are refractory to any therapy. Future research should focus on the identification of prognostic biomarkers that help us to tailor an individualized treatment for each type of patient and in the search of new disease activity indices that help us to monitor the response to the therapy more closely.

KEYWORDS:

• Adult-onset Still disease
• anakinra
• anti-IL6-receptor tocilizumab
• anti-TNF-α drugs
• biologics
• glucocorticoids

Article highlights

• AOSD is a heterogeneous disorder at the crossroads between autoinflammatory and autoimmune diseases.

• Glucocorticoids constitute the first line of treatment for AOSD.

• Conventional DMARDs, especially MTX, are often considered in refractory cases or as GC-sparing agents.

• Biologic agents must be considered in the management of AOSD refractory to GC and conventional DMARDs, since the ultimate goal in the management of AOSD is to achieve sustained remission and reduce the risk of relapses and life-threatening complications.

• The development of composite indices based on multiple biomarkers to detect disease activity definitely could support rational decision making in the treatment of AOSD.

• TCZ, a humanized anti-IL-6 receptor antagonist, is an effective drug for the global treatment of AOSD, both for systemic and joint manifestations, as well as for some severe life-threatening manifestations of the disease.

• Overall, the benefit/risk ratio and safety profile of TCZ is favorable and similar to that described in RA and other rheumatic diseases. However, some cases of MAS have been described after the start of treatment with TCZ as well as with other biological agents.

• Besides the currently available therapeutic options, new biologic agents against IL-18 or small molecules against Jak-1/Jak-2 may be additional therapeutic options in AOSD.

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Acknowledgments

The authors thank Roche Farma Spain, and especially Sofia García and Sagrario García-Arisco, for their technical support.

Declaration of interest

S Castañeda has received grants/research supports from MSD and Pfizer, consultation fees/participation in company sponsored speaker´s bureau from Amgen, MSD, Lilly, Pfizer, Roche, Sobi and UCB, and travel aids for Congresses from BMS, MSD, Lilly, Pfizer and Roche. MA Gonzalez-Gay has received grants/research supports from Abbvie, MSD, and Roche, and had consultation fees/participation in company sponsored speaker´s bureau from Abbvie, Pfizer, Roche, Sanofi, Lilly, Sobi, Celgene and Novartis. The authors have no other relevant affiliations or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. The remaining authors have nothing to declare.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.