Long-Term Efficacy and Safety of Canakinumab in Patients with Active Recurrent or Chronic TNF Receptor-Associated Periodic Syndrome

Marco Gattorno¹, Marco Cattalini², L. Obici³, Roberto Barcellona⁴, Antonio Speziale⁵, Yolandi Joubert⁵, Guido Junge⁵ and Helen Lachmann⁶, ¹Pediatric Rheumatology, G. Gaslini Institute, Genova, Italy, ²Pediatric Clinic, University of Brescia, Brescia, Italy, ³Amyloid Centre, Policlinico S. Matteo, Pavia, Italy, ⁴Hospital of Sciacca, Sciacca, Italy, ⁵Novartis Pharma AG, Basel, Switzerland, ⁶UK National Amyloidosis Centre, University College London Medical School, London, United Kingdom

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

Keywords: IL-1, Traps and canakinumab

Session Information

Date: Sunday, November 8, 2015

Title: Miscellaneous Rheumatic and Inflammatory Diseases I

Session Type: ACR Concurrent Abstract Session

Session Time: 2:30PM-4:00PM

Background/Purpose: Tumor
necrosis factor (TNF) receptor-associated periodic syndrome (TRAPS) is a rare,
dominantly inherited periodic fever syndrome characterized by recurrent attacks
of fever associated with rash, musculoskeletal and abdominal pain,
conjunctivitis, and periorbital edema.¹ Nonsteroidal
anti-inflammatory drugs and high-dose corticosteroids are often used for acute
symptomatic relief but are limited by their well-known side effects. TNF
inhibitors have been shown to be effective in some patients, however, their
efficacy tends to decrease over time.^2–4 Here
we present the long-term safety and efficacy of canakinumab
(CAN) in patients with active TRAPS. The primary objective was to assess if CAN
induces complete or almost complete response in patients on Day 15. Secondary
objectives included clinical and serological remission, changes in signs and
symptoms of TRAPS and physician’s global assessment (PGA) over time, as well as
assessment of adverse events (AEs) and serious AEs (SAE) reported.

Methods: This was
an open-label single treatment arm study with a 4-month treatment period, a
5-month follow-up period (treatment withdrawal), and a 24-month long-term
treatment period. Patients with active TRAPS received monthly CAN 150 mg (2
mg/kg for patient ≤40 kg) subcutaneously.

Results: At baseline,
PGA of TRAPS activity showed 13 (65%) patients with mild, 6 (30%) with moderate
and 1 (5%) with severe TRAPS; with chronic TRAPS being present in 11 (55%)
patients. Of all the 20 patients who received
CAN, 18 (90%) completed the study. On day 15, 19 patients (95%) achieved a complete
or almost complete response, while 20 (100%) and 12 (60%) patients had clinical
and serological remission, respectively (Table). Disease activity decreased in
the long-term treatment period, and most patients experienced absent, minimal,
or mild disease activity. At the end of the long-term period, all patients had absent
(84.2%) or minimal (10.5%) disease activity. CRP and SAA levels were highest at
baseline and decreased rapidly with treatment. In total, 12 patients (60%)
experienced study drug-related AEs, predominantly upper respiratory tract
infections. Seven patients (35%) experienced SAEs; none were related to the study
drug. There were no AEs leading to discontinuation and no deaths were reported during
the study.

Table. Clinical and serological remission on Days 8 and 15
Response criteria	Canakinumab N=20, n (%)	95% CI^*
Complete or almost complete response (Day 8)	16 (80)	(56.3, 94.3)
Complete or almost complete response (Day 15)	19 (95)	(75.1, 99.9)
Proportion of patients with complete clinical remission (PGA score ≤1; Day 8)	18 (90)	(68.3, 98.8)
Proportion of patients with complete clinical remission (PGA score ≤1; Day 15)	20 (100)	(83.2, 100.0)
Proportion of patients with both CRP and SAA ≤10 mg/L (Day 8)	7 (35)	(15.4, 59.2)
Proportion of patients with both CRP and SAA ≤10 mg/L (Day 15)	12 (60)	(36.1, 80.9)
Proportion with complete or almost complete response on Day 15 in the patient subgroup without complete or almost complete response on Day 8	4 (100)	(39.8, 100.0)
Complete response: Clinical (PGA ≤minimal) and serological (CRP and/or SAA <10 mg/L) remission Almost complete response: Clinical (PGA ≤minimal) and partial serological (≥70% reduction of baseline CRP and/or SAA) remission ^*95% CI (Clopper–Pearson) CI, confidence interval; CRP, C-reactive protein; PGA, physician’s global assessment; SAA, serum amyloid A

Conclusion: Canakinumab
demonstrated rapid disease control in terms of clinical signs and symptoms, and
serological response in patients with active TRAPS through the treatment and
long-term treatment periods. No new safety signals were reported during this
long-term study. Safety profile was consistent with those reported in other canakinumab
studies.

References:

1.
Williamson LM, et al. Q J Med. 1982;51:469-4802.

2.
Ter Haar NM, et al. Curr Opin Rheumatol. 2014;26(3):252-8

3. Simon A, et al. Am
J Med. 2004;117:208-10.

4. Jacobelli S, et al. Rheumatology
(Oxford). 2007;46(7):1211-2

Disclosure: M. Gattorno, Novartis Pharmaceutical Corporation; SOBI, 2,Novartis Pharmaceutical Corporation; SOBI, 8; M. Cattalini, Novartis Pharmaceutical Corporation: SOBI, 5,Novartis Pharmaceutical Corporation, 8; L. Obici, Novartis Pharmaceutical Corporation, 5,Novartis Pharmaceutical Corporation, 8; R. Barcellona, None; A. Speziale, Novartis, 3; Y. Joubert, Novartis Pharmaceutical Corporation, 3; G. Junge, Novartis., 3; H. Lachmann, Novartis Pharmaceutical Corporation, 5.

To cite this abstract in AMA style:

Gattorno M, Cattalini M, Obici L, Barcellona R, Speziale A, Joubert Y, Junge G, Lachmann H. Long-Term Efficacy and Safety of Canakinumab in Patients with Active Recurrent or Chronic TNF Receptor-Associated Periodic Syndrome [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/long-term-efficacy-and-safety-of-canakinumab-in-patients-with-active-recurrent-or-chronic-tnf-receptor-associated-periodic-syndrome/. Accessed .

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