The role of synthetic drugs in the biologic era: therapeutic strategies for treating juvenile idiopathic arthritis

ABSTRACT

Introduction: Juvenile idiopathic arthritis is the most frequent chronic rheumatic disease in childhood. Synthetic disease modifying drugs (DMARDs) have been used in its treatment since the 1980s and have led to substantial improvement of quality of life and disease outcome. Recent pharmacological research has focused on newer medications, especially biologic agents.

Areas covered: Synthetic DMARDS, especially methotrexate, rightfully remain the first-line treatment of most categories of juvenile arthritis, as attested by several international guidelines. A substantial body of evidence supports these medications, and recent research tries to clarify their optimal use in the clinical setting, both as monotherapy and in combination with biologics. In addition, new forms of synthetic DMARDs are in the research pipeline, or are already used for rheumatoid arthritis.

Expert Opinion: Methotrexate remains the preferred first-line medication for polyarticular arthritis, with leflunomide as a viable alternative in case of intolerance or toxicity, despite lack of approval in Europe and the US.

Sulfasalazine and hydroxychloroquine are used only rarely in clinical practice, considered in combination with methotrexate if biologics are not available. New synthetic DMARDS are in the research pipeline for JIA, in the form of small molecules.

KEYWORDS:

• Hydroxychloroquine
• juvenile idiopathic arthritis
• leflunomide
• methotrexate
• non-steroidal anti-inflammatory drugs
• sulfasalazine
• synthetic DMARDS
• tofacitinib

Article highlights

• Despite advances in biological treatments, synthetic disease-modifying antirheumatic drugs (DMARDS), especially methotrexate (MTX), represent the mainstay of treatment for most categories of juvenile idiopathic arthritis (JIA).

• MTX is the preferred first-line medication for polyarticular arthritis and is present as such in practically all guidelines and consensus papers.

• Leflunomide is a viable alternative to MTX in case of intolerance or toxicity, despite lack of approval in Europe and the US.

• Sulfasalazine and hydroxychloroquine are used only rarely in clinical practice due to an unfavorable benefit-to-risk ratio and, in case of hydroxychloroquine, questionable efficacy. They can be considered in combination with MTX if biologics are not available.

• New synthetic DMARDs are in the research pipeline for JIA in the form of small molecules.

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Declaration of interest

B Hugle has received payment for lectures, grants (including travel grants) and unrestricted funding for investigator-initiated studies from Novartis, Pfizer and Roche. The authors have no other 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 apart from those disclosed.