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. 2019 Apr 2:10:296.
doi: 10.3389/fphar.2019.00296. eCollection 2019.

Long-Term Retention Rate of Anakinra in Adult Onset Still's Disease and Predictive Factors for Treatment Response

Antonio Vitale  1 , Giulio Cavalli  2   3 , Serena Colafrancesco  4 , Roberta Priori  4 , Guido Valesini  4 , Lorenza Maria Argolini  5 , Elena Baldissera  3 , Elena Bartoloni  6 , Daniele Cammelli  7 , Giovanni Canestrari  8 , Jurgen Sota  1 , Elena Cavallaro  9 , Maria Grazia Massaro  10 , Piero Ruscitti  11 , Paola Cipriani  11 , Ginevra De Marchi  9 , Salvatore De Vita  9 , Giacomo Emmi  7 , Gianfranco Ferraccioli  8 , Micol Frassi  12 , Roberto Gerli  6 , Elisa Gremese  8 , Florenzo Iannone  13 , Giovanni Lapadula  13 , Giuseppe Lopalco  13 , Raffaele Manna  10 , Alessandro Mathieu  14 , Carlomaurizio Montecucco  15 , Marta Mosca  16 , Ilaria Piazza  17 , Matteo Piga  14 , Irene Pontikaki  5 , Micol Romano  5 , Silvia Rossi  15 , Maurizio Rossini  17 , Elena Silvestri  7 , Chiara Stagnaro  16 , Rosaria Talarico  16 , Angela Tincani  12 , Ombretta Viapiana  17 , Gianfranco Vitiello  7 , Paola Galozzi  18 , Paolo Sfriso  18 , Carla Gaggiano  19 , Donato Rigante  20 , Lorenzo Dagna  2   3 , Roberto Giacomelli  11 , Luca Cantarini  1
Affiliations

Long-Term Retention Rate of Anakinra in Adult Onset Still's Disease and Predictive Factors for Treatment Response

Antonio Vitale et al. Front Pharmacol. .

Abstract

Background: Anakinra (ANA) is an effective treatment choice in patients with adult onset Still's disease (AOSD). Variables affecting treatment survival include loss of efficacy or adverse events, but also the decision to discontinue treatment after long-term clinical remission. Objectives: Aims of this study were: (i) to assess the drug retention rate (DRR) of ANA during a long-term follow-up looking for any difference related to the line of biologic treatment, the concomitant use of conventional disease modifying anti-rheumatic drugs (cDMARDs) and the different type of AOSD (systemic versus chronic articular); (ii) to identify predictive factors of lack of efficacy, loss of efficacy, and ANA withdrawal owing to long-term remission. Methods: AOSD patients classified according with Yamaguchi criteria and treated with ANA were retrospectively enrolled in 18 Italian tertiary Centers. Demographic, laboratory, clinical and therapeutic data related to the start of ANA (baseline), the 3-month assessment and the last follow-up visit while on ANA treatment were retrospectively collected and statistically analyzed. Results: One hundred and forty-one AOSD patients (48 males, 93 females) treated with ANA for a mean period of 35.96 ± 36.05 months were enrolled. The overall DRR of ANA was 44.6 and 30.5% at the 60- and 120-month assessments, respectively, with no significant differences between: (i) biologic naïve patients and those previously treated with other biologics (log-rank p = 0.97); (ii) monotherapy and concomitant use of cDMARDs (log-rank p = 0.45); (iii) systemic and chronic articular types of AOSD (log-rank p = 0.67). No variables collected at baseline could predict primary inefficacy, while the number of swollen joints at baseline was significantly associated with secondary inefficacy (p = 0.01, OR = 1.194, C.I. 1.043-1.367). The typical AOSD skin rash was negatively related with ANA withdrawal owing to long-term remission (p = 0.03, OR = 0.224, C.I. 0.058-0.863). Conclusion: Long-term DRR of ANA has been found excellent and is not affected by different lines of biologic treatment, concomitant use of cDMARDs, or type of AOSD. The risk of losing ANA efficacy increases along with the number of swollen joints at the start of therapy, while the typical skin rash is a negative predictor of ANA withdrawal related to sustained remission.

Keywords: autoinflammatory diseases; canakinumab; innovative biotechnologies; interleukin-1; personalized medicine; systemic onset juvenile idiopathic arthritis.

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Figures

FIGURE 1
FIGURE 1
Reverse Kaplan–Meier survival curve showing the cumulative risk for loss of efficacy to Anakinra treatment over time. The “time 0” is represented by the start of ANA treatment; the “event” corresponds to treatment withdrawal due to secondary inefficacy.
FIGURE 2
FIGURE 2
Kaplan–Meier survival curves describing the cumulative retention of Anakinra over the whole follow-up period taking into account all causes of treatment withdrawal (blue line), only adverse events and lack/loss of efficacy (green line), and only lack and loss of efficacy (red line). The “time 0” is represented by the start of ANA treatment; the “event” corresponds to treatment withdrawal.
FIGURE 3
FIGURE 3
Cumulative DRR of Anakinra in patients with AOSD undergoing their first biologic agent and those previously treated with other biologics.
FIGURE 4
FIGURE 4
Cumulative DRR of Anakinra in patients with AOSD concomitantly administered with cDMARDs and those treated with IL-1 blockade as monotherapy at the start of ANA treatment (A) and at the last follow-up visit (B).
FIGURE 5
FIGURE 5
Cumulative DRR of Anakinra in patients with AOSD in both systemic and chronic articular type.
FIGURE 6
FIGURE 6
Arthritis involving the right hand in a male patient with AOSD. In particular, the second and third metacarpophalangeal joints, as well as the distal interphalangeal joint of the index finger and the proximal interphalangeal joints of the middle and annular fingers are swollen.
FIGURE 7
FIGURE 7
Maculopapular skin rash involving the lower limbs in a female patient suffering from AOSD.
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