Investigational agents for polymyalgia rheumatica treatment: assessing the critical needs for future development

ABSTRACT

Introduction

Polymyalgia rheumatica (PMR) is an inflammatory rheumatic disorder characterized by pain and stiffness in the shoulder and pelvic girdles, constitutional symptoms, and elevated acute-phase reactants. Glucocorticoids (GCs) remain the first-choice treatment for PMR, but relapses are common. Identification of steroid-sparing agents is therefore of utmost importance.

Areas covered

The efficacy of conventional immunosuppressive drugs is controversial. The use of interleukin (IL)-6 receptor inhibitors proved to be effective and safe in treating PMR patients. Currently, there are 12 ongoing clinical trials exploring potential treatments such as leflunomide, low-dose IL-2, rituximab, abatacept, secukinumab, Janus kinase inhibitors, and selective inhibitors like SPI-62 and ABBV 154.

Expert opinion

The high efficacy of IL-6 R receptor inhibitors as well as the numerous drug trials currently recruiting suggest that several therapeutic options will be available in the near future. Accurate diagnosis and early stratification of PMR patients according to the giant cell arteritis-PMR Spectrum Disease ‘GPSD’ and potential risk factors for relapsing disease or GC-related adverse events are crucial to identify patients who would benefit most from GC-sparing agents. The development of internationally accepted definitions for remission and relapse is urgently needed. Early referral strategies to specialist settings would improve disease stratification and personalized treatment

KEYWORDS:

• Polymyalgia rheumatica
• ‘GCA-PMR spectrum disease’ (GPSD)
• biologic agents
• PMR clinical trials
• B-cell depletion therapy
• JAK inhibitors
• tocilizumab
• sarilumab

Article highlights

• Despite the traditional perception of polymyalgia rheumatica as a “mild” disease, accumulating evidence reveals a significant disease burden characterized by relapses and prolonged glucocorticoids exposure.

• A correct diagnosis and early stratification of patients according to the GPSD spectrum are essential to identify those patients who would benefit most from glucocorticoid-sparing agents.

• The efficacy of conventional DMARDs is uncertain, and biologic agents such as IL-6 inhibitors are showing promise, though regulatory approval is pending.

• Optimizing referral, diagnostic, and management strategies is imperative to reduce steroid burden while achieving remission, the primary treatment goal.

• The development of shared and precise definitions of disease activity would enable better management of patients in daily clinical practice and the planning of more effective clinical trials.

Declaration of interest

Christian Dejaco is a Consulting/speaking fees from AbbVie, Eli Lilly, Janssen, Sparrow, Novartis, Pfizer, Roche, Galapagos and Sanofi; grant support from AbbVie. The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

A reviewer on this manuscript has disclosed they have served on the Speakers Bureau for: AbbVie, BMS, Galapagos, Lilly, Novartis, Nordic, Pfizer, Roche-Chugai, Sanofi, UCB. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.