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Abstract Number: 1242

Switching Biologic Agents in Refractory Adult-Onset Still’s Disease: Efficacy and Safety in a Cohort of 20 Patients at a Single Referral Center

Giulio Cavalli1, Stefano Franchini1, Corrado Campochiaro1, Elena Baldissera2, Lorenzo Dagna3 and Maria Grazia Sabbadini3, 1Internal Medicine and Clinical Immunology, Vita-Salute San Raffaele University, Milan, Italy, 2Clinical immunopathology and advanced medical therapeutics, San Raffaele Scientific Institute, Milan, Italy, 3Internal Medicine and Clinical Immunology, Vita-Salute San Raffaele University, Milano, Italy

Meeting: 2014 ACR/ARHP Annual Meeting

Keywords: Adult-onset Still's disease, Anakinra, biologic drugs and tocilizumab, DMARDs

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Session Information

Title: Miscellaneous Rheumatic and Inflammatory Diseases

Session Type: Abstract Submissions (ACR)

Background/Purpose

No data is available on the long-term clinical outcome of Adult-Onset Still’s Disease (AOSD) patients treated with biological drugs, nor on the efficacy and safety of switching biologics in the management of refractory cases. We aimed to evaluate the efficacy and safety of switching biological agents in a large, monocentric cohort of 20 patients with refractory AOSD.

Methods

Twenty Italian AOSD patients treated with biological agents were followed-up at our Institution for at least 24 months. For each case we retrospectively evaluated the disease course, the efficacy of treatment, and the potential adverse effects. Efficacy was evaluated as “Complete response” (CR: absence of articular and systemic manifestations, normalization of inflammatory indexes, >50% reduction in the corticosteroid dosage); “Partial response” (PR: clinical improvement without normalization of inflammatory markers, nor >50% reduction in the dose of steroids); or “Treatment failure” (TF: persistence/worsening of disease manifestations, persistent elevation of inflammatory markers, or need for an increased dose of corticosteroids despite 2 months of treatment).


Results

The median duration of follow-up was 5 years. In 12 patients a single biological drug induced a clinical response. Five patients were switched to a different biologic because of lack of efficacy. In 3 patients, a third biologic was necessary to achieve disease control. Biologics eventually determined a clinical response in all patients. Anakinra was used in all 20 patients; etanercept, tocilizumab and adalimumab was used in 6, 4, and 1 patient, respectively. Sixteen patients responded to anakinra (80%; CR 70%; PR 10%). Four patients (20%) did not respond to anakinra, and of these three responded to tocilizumab, and one responded to adalimumab. Etanercept was used unsuccessfully in six patients. Patients with systemic manifestations showed better responses than patients with chronic articular disease (p<0.05). Overall, biologic agents determined a significant reduction in the dose of the associated therapy with corticosteroids (p<0.0001) and DMARDs (p<0.05). Three patients experienced herpes zoster reactivation.
 

Conclusion

Biological agents represent a pivotal therapeutic resource for AOSD patients refractory to conventional treatment. Although the biologic drug of choice may prove ineffective, switching between biologics ultimately resulted in a clinical response in all patients without significant adverse effects, hence the importance of pursuing a tailored treatment approach. Although IL-1 blockade with anakinra represents the mainstay of treatment, IL-6 blockade may be more effective in patients with chronic articular involvement. Both anakinra and tocilizumab were more effective than TNF-α blockers. Patients with SD are more likely to respond favorably to biologics than patients with CAD. Different pathogenic mechanisms underlying SD and CAD, or the development of irreversible articular damage in CAD, may account for the differences in response to treatment.
 

References:
 Al-Homood IA. Biologic treatments for adult-onset Still’s disease. Rheumatology 2013.


Disclosure:

G. Cavalli,
None;

S. Franchini,
None;

C. Campochiaro,
None;

E. Baldissera,
None;

L. Dagna,
None;

M. G. Sabbadini,
None.

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