Adult-onset Still’s Disease (AoSD), alternatively known as systemic-onset juvenile idiopathic arthritis, is a rare systemic inflammatory disorder of unknown etiology. There are three main patterns of AoSD’s clinical course: monophasic, intermittent, and chronic. Although there is an approximately equal distribution in each category, some studies have shown the chronic articular pattern to be more common.
According to the Arthritis Foundation (n.d.), AoSD is a type of arthritis with symptoms like fever, rash, and joint pain and was thought to be autoimmune or autoinflammatory. According to Orphanet (n.d.), the estimated AoSD prevalence is 1–9/100,000 population, and women are affected marginally more than men. In addition, as per the statistics of the National Institute of Health (NIH) and Genetic and Rare Disease Information Center (GARD) (n.d.), it has been estimated that about 1–4 people in one million have AoSD.
Thorough clinical assessment of characteristic symptoms and patient history and differentiating other possible disorders constitute the crux of AoSD diagnosis. The ‘‘gold standard’’ for diagnosing AoSD remains blood tests that reveal characteristic changes to blood cells. Erythrocyte sedimentation rate is a common blood test for individuals suspected of having an inflammatory disorder.
AoSD is a multigenic autoinflammatory disorder that stands at the junction of autoinflammatory and autoimmune diseases and involves innate and adaptive immune systems. The treatment of AoSD is currently centred on nonsteroidal anti-inflammatory drugs (NSAIDs), steroids, and antirheumatic agents. According to older studies, NSAID as monotherapy effectively controls disease in only 7–15% of patients, and most patients are treated with steroids at some point in their disease course, with responses ranging from 76% to 95%, making corticosteroids the cornerstone of AoSD therapy.
Many different therapies have been investigated in Adult-onset Still’s Disease treatment market, but none has proven effective consistently. Therefore, a variety of monotherapies and combinational therapies are used to treat the affected population. The first-line therapy of AoSD consists of corticosteroid and NSAID, while the second-line therapy includes methotrexate (MTX) or cyclosporin A. In the case of refractory AoSD, the preferred option is the usage of IL-1 or IL-6 antagonists along with more biologics varying among individuals.
Macrophage activation syndrome (MAS) is a life-threatening manifestation of AoSD. It is a kind of cytokine storm caused by uncontrolled activation and expansion of T lymphocytes and macrophages. It is frequently associated with systemic juvenile idiopathic arthritis (sJIA), systemic lupus erythematosus, and other rheumatic diseases. The traditional therapy for MAS includes mega-dose corticosteroids followed by a slow reduction and combinations with immune modulators, especially cyclosporine; IV immunoglobulin is required in some patients related to certain types of infection. To summarize, the work-up management of AoSD includes NSAIDs, corticosteroids, disease-modifying antirheumatic drugs (DMARDs), MTX, interleukins, tumor necrosis factors, etc., along with timely monitoring of the clinical responses and adverse events.
While the Adult-onset Still’s Disease treatment market include Canakinumab (Novartis), Anakinra (Swedish Orphan Biopharma), and tocilizumab (Roche), the upcoming therapies comprise CERC 007 (Cerecor) and Tadekinig Alfa (AB2 Bio).
Tadekinig alfa has been granted Orphan Drug Designation (ODD) by the FDA to treat hemophagocytic lymphohistiocytosis (HLH) and Still’s disease, including AoSD and sJIA. The EMA has also granted it an ODD to treat HLH. Furthermore, the FDA has granted Tadekinig alfa Breakthrough Therapy Designation to treat monogenic, IL-18 associated autoinflammatory conditions with ongoing systemic inflammation and Pediatric Rare Disease Designation to treat primary HLH.
Rare diseases defined as affecting <200,000 people in the US, present unique challenges to the medical community. Specifically, affected populations encounter difficulty obtaining timely and accurate diagnoses, struggle to find reliable resources or experienced providers, and often pay exorbitant fees for what drugs become available. Moreover, as with many rare medical conditions, progress concerning AoSD has also been hampered by insufficient enrollment in large randomized trials. Consequently, challenges regarding diagnosis, monitoring, and treatment of the disease and a lack of updated classification criteria persist.