Rheumatologists primarily treat patients diagnosed with adult-onset Still’s disease (AOSD) empirically and based on sporadic cases, retrospective case studies, and small clinical trials.
“You want to help these people,” said Nilanjana Bose, MD, MBA, a rheumatologist at Lonestar Rheumatology in Houston. “Oftentimes these patients go from doctor to doctor and no one knows what is going on.”
Christopher R. Morris, MD, a rheumatologist in private practice at Arthritis Associates in Kingsport, Tennessee, emphasized the importance of starting treatment as soon as the patient has been diagnosed. “I think it is a reasonably treatable disease if we get the patients on the medications promptly,” he said.
Expert consensus indicates that patients with AOSD benefit from treatment with non-biological pharmacotherapies, including glucocorticoids, methotrexate, and calcineurin inhibitors. Corticosteroids are initially used to control the severe inflammation, and methotrexate and calcineurin inhibitors are used as steroid-sparing agents.
Bose treats patients with mild to moderate disease with steroids and methotrexate. While she has found that patients respond well to steroids, symptoms often return while tapering steroids; therefore, she prefers to add methotrexate. In contrast, Morris begins by prescribing both prednisone and azathioprine. His goal is remission, as indicated by normalized levels of liver enzymes, ferritin, and inflammation markers. Patients should also experience relief from fevers and rash. He noted that corticosteroids often work quickly and, if they are effective, he does not escalate treatment.
Studies have shown that disease-modifying antirheumatic drugs (DMARDs) such as methotrexate, cyclosporine A, and leflunomide can induce a clinical response and manage life-threatening complications. Moreover, a case study of a patient with AOSD complicated by covid-19 found that the patient responded quickly to prompt initiation of corticosteroids and methotrexate.
Clinicians have also found that colchicine alone or in combination with other treatments can be effective for refractory AOSD. Unfortunately, since 2src% to 3src% of AOSD patients are refractory to conventional therapies, rheumatologists must often turn to biologics.
Research has indicated that interleukin-1β (IL-1β) acts as a key pro-inflammatory cytokine in the immunopathogenesis of AOSD, and so many rheumatologists believe that therapy that targets this cytokine has the highest likelihood of achieving therapeutic effect. Consistent with this, Morris said he found that IL-1 inhibitors are very effective in the treatment of AOSD. Canakinumab (Ilaris), a long-acting IL-1β inhibitor that is administered as a subcutaneous injection once every 4 weeks, was the first treatment to be approved for AOSD.
Other IL-1 inhibitors may also be effective, noted Morris, but since AOSD is a rare disease, there is unlikely to ever be a head-to-head comparison of efficacy. Anakinra (Kineret), for example, is a recombinant form of the human IL-1 receptor antagonist that blocks biological activity of both IL-1β and IL-1α. Among other conditions, it is indicated for the treatment of moderate to severe active rheumatoid arthritis (RA) in adults when one or more other drugs for RA have not worked. Bose has prescribed the daily subcutaneous injection to help control the inflammation associated with AOSD, especially if the disease has evolved into an RA-like presentation.
Rilonacept (Arcalyst), a soluble IL-1 trap molecule that binds with a high affinity to both IL-1α and IL-1β, is also an option for patients. Bose noted that since patients often have unique responses to the different biologics, it is worthwhile to try more than one.
Morris explained that if patients do not respond to IL-1 inhibitors, he then turns to IL-6 inhibitors, and then tumor necrosis factor (TNF) inhibitors. Research has shown that the recombinant humanized anti-IL-6 receptor monoclonal antibody tocilizumab (Actemra) can be effective in reducing both systemic and joint symptoms. In addition, treatment with TNF-α inhibitors can be effective in resolving clinical symptoms such as fever, arthralgias, skin rashes, myalgias, and hepatosplenomegaly.
Other biologics with some history of use in patients with AOSD include the IL-18 inhibitor tadekinig alfa, which has been found to be effective in achieving remission of fever. While rheumatologists are also experimenting with the use of the Janus kinase (JAK) inhibitors baricitinib (Olumiant) and tofacitinib (Xeljanz), published data on their efficacy and safety in patients with AOSD are sparse, and, unfortunately, the rarity of AOSD continues to limit the study of these newer treatments.
Of note, research has shown that treatment with biologics may come with some risk. Rheumatologists have documented that some patients with AOSD appear to have an anaphylactic reaction to treatment with IL-1 and IL-6 inhibitors, and this reaction may trigger lung involvement in AOSD. Unfortunately, since AOSD-lung disease is rare, there are no evidence-based recommendations for its treatment. Moreover, alveolar hemorrhage and pulmonary arterial hypertension tend to be refractory to glucocorticoid treatment.
Morris and Bose reported no relevant conflicts of interest.