CC BY
23The use of Canakinumab in treating resistant gouty disease in patients with limited therapeutic options: The experience of the Rheumatology Clinic of Asklipeion General Hospital of Voula, Greece
Evangelos Theotikos, Ioannis Raftakis, Antonia Elezoglou, Christodoulos Antoniadis
Mediterr J Rheumatol 2017; 28(1):48-51
mediterranean journal
of RHEUMATOLOGY
s-ISSN: 2529-198X
E-ISSN: 2529-198X
MEDITERRANEAN JOURNAL OF RHEUMATOLOGY March 2017 | Volume 28 | Issue 1
MEDITERRANEAN journal
of RHEUMATOLOGY
28 1
2017
© Theotikos E, Raftakis I, Elezoglou A, Antoniadis C
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International L
©CD®
CASE SERIES
The use of Canakinumab in treating resistant gouty disease in patients with limited therapeutic options: The experience of the Rheumatology Clinic of Asklipeion General Hospital of Voula, Greece
Evangelos Theotikos, Ioannis Raftakis, Antonia Elezoglou, Christodoulos Antoniadis
Asklipeion General Hospital of Voula, Athens, Greece
ABSTRACT
Gout is an autoinflammatory disease caused by monosodium urate mono hydrate crystal deposition in tissues or the supersaturation of extracellular fluids of uric acid. In this study, we are going to report the experience of the Asklepeion Voula Rheumatology Clinic, treating four patients with gouty arthritis who received Canakinumab.
Mediterr J Rheumatol 2017;28(1):48-51 https://doi.org/10.31138/mjr.28.1A8
Article Submitted 05/09/2016; Revised form 15/12/2016; Accepted 19/12/2016
Keywords: Gout, Canakinumab, Uric Acid, Patients.
The crystal deposition of gout occurs when uric acid exceeds its solubility limit (approximately 6,8 mg/dl 37o C).1,2 Gouty disease affects adult males mostly and postmenopausal women, with higher incidence in the fifth decade of life (men/women 7-9/11). It is rare in males <30 years old and premenopausal women.3,4 The clinical spectrum of gout includes asymptomatic hy-peruricemia, acute intermittent gout, and chronic topha-ceous gout. Clinical associations include renal disease, hypertension, obesity and hyperlipidemia.5 The diagnosis of gout is based on the patient's medical history, clinical examination, radiographic imaging (mostly in chronic situations), with the presence of tophi, bony erosions, soft tissue swelling, ultrasound (double contour sign) and ar-throcentesis (inflammatory synovial fluid with MSU crystals on compensated polarized microscopy).6 Differential diagnosis of gout includes septic arthritis, pseudogout, traumatic arthritis, rheumatoid arthritis (with
polyarticular presentation), seronegative ar-thritis.6
Corresponding author:
Evangelos Theotikos The treatment of gout
Rheumatol°gy Resident can be non-pharma-
Asclepeion Voulas "
Leof. Vasileos Pavlou 1, Vari Voula cological (special diet
Vouliagmeni 166 73, Greece and changes in lifestyle
Tel.: +30 21 0892 3000, +30 6937030493 d U . d ......ttoiyie,
E-mail: theotikosevangelos@hotmail.com dealing with primary
causes, avoiding specific drugs, treating comorbidities) and pharmacological. Pharmacological therapy of acute gouty arthritis includes NSAIDS, glucocorticosteroids and Colchicine. On failure of first line medication or prohibition of use due to comorbidities, second line medication can be used such as Anakinra and Canakinum-
ab.5,7,8,9,-io
Canakinumab is a fully human anti-IL-1 b monoclonal antibody with isotype IgG1/k. It binds with great affinity specifically to human IL-1b and neutralizes its biological activity excluding its interaction with IL-1 receptors preventing gene activation and production of inflammatory mediators.2,7,9,10 It is indicated for the symptomatic treatment of adult patients with frequent flares of gouty arthritis (3 in the last 12 months) when NSAIDS, colchi-cine and the frequent use of glucocorticosteroids are contraindicated.5,7,11,12 The side effects studies indicated an elevated incidence for infections, but not opportunistic. Lack of reactions at the point of injection, and no increased incidence of neoplasms was observed. A small increase of uric acid levels, pancytopenia and lipid change was noted, but all were reversible.1,6,10 Here, we are going to report the experience of the Asklepeion Voula Rheumatology Clinic treating four patients with gouty arthritis who received Canakinumab. The first patient, 54 years old, experienced five flares of
48 Cite this article as: Theotikos E, Raftakis I, Elezoglou A, Antoniadis C. The use of Canakinumab in treating resistant gouty disease in patients with limited therapeutic options: The experience of the Rheumatology Clinic of Asklipeion General Hospital of Voula, Greece. Mediterr J Rheumatol 2017;28(1):48-51.
THE USE OF CANAKINUMAB IN TREATING RESISTANT GOUTY DISEASE IN PATENTS WITH LIMITED THERAPEUTIC OPTIONS: THE EXPERIENCE OF THE RHEUMATOLOGY CLINIC OF ASKLIPEION GENERAL HOSPITAL OF VOULA, GREECE
gouty arthritis within the last year, resistant to treatment with NSAIDS, colchicine and glucocorticosteroids. At the time of his first hospitalization he had arthritis of 2nd right metacarpophalangeal and 3rd left proximal interphalan-geal joints and both knees and ankles. Microscopic synovial fluid analysis, after arthrocentesis of the left ankle revealed MSU crystals.
He initially received colchicine and NSAIDS which were stopped due to elevation of liver enzymes. He then received per os glucocorticosteroids, 0,5 mg/kg according to the ACR 2012 guidelines, plus allopurinol. When the dose of glucocorticosteroids was lowered to 15mg of prednisone he was hospitalized for a second time with arthritis of second right metacarpophalangeal joint and olecranon bursitis. The ultrasound of 2nd metacar-pophalangeal joint indicated Grade 1 synovitis and the presence of tophi. He then received Canakinumab with complete symptoms recovery (concomitant use only of allopurinol).
The second patient, 32 years old, suffers from tophaceous juvenile gout from the age of 4 (no genetic test was performed due to high cost). His medical history includes at least three flares of gouty arthritis per year from a young age, nephrocalcinosis, lithotripsy at the age of 10, the use of allopurinol, colchicine, NSAIDS without response. He has multiple tophi of proximal and distal in-terphalangeal joints in both hands (Figure 1). Radiolog-ically, he has multiple bony erosions in the carpal bones with overhanging edge sign (Figure 2). Ultrasound revealed double contour sign over the 2nd metacarpopha-langeal bone (Figure 3), over the knee cartilage (Figure 4) and a big tophus over the metatarsophalangeal joint (Figure 5).
The patient had progressively worsening symptoms with arthritis of both wrists, proximal interphalangeal joints, distal interphalangeal joints and both knees, initially treated with glucocorticosteroids 0,5 mg/kg according to the ACR 2012 guidelines but was non-responsive when glu-cocorticosteroid doses were reduced to 20 mg prednisone. He also developed intolerance to the use of colchicine and NSAIDS with abnormal liver function tests (AST 227, ALT 638, TGT 156) which resolved after removal. Since then, he has received 3 doses of Canakinumab with complete symptoms resolution with no flares after 3 months.
The third patient, 49 years old, has had hyperuricemia for 25 years, gout for 10 years and has multiple flares of gouty arthritis with polyarthritis of both small and large joints (metatarsophalangeals, ankles, knees, elbows). He also suffers from Type 2 insulin-dependent diabetes for 10 years and chronic kidney failure (stage 4) for 3 years. Despite the treatment with allopurinol 100 mg, prezolon 20 mg and colchicine 1/2 mg daily (adapted to chronic kidney failure) he was hospitalized 2 times with resistant polyarthritis (metatarsophalangeal joints, ankles,
Figure 1: Patient 2. Multiple tophi of proximal and distal interphalangeal joints.
Figure 2: Patient 2. Multiple carpal bones erosions with overhanging edge sign.
ASKLIPIEIO VOULA HOSPITAL
B CHI Frq 12.0 MHz Gn 66 - E/A 2/1 Map D/0/0 D 2.5 cm DR 75 FR 21 Hz AO 100% ■ XBeam On
Figure 3: Patient 2. Ultrasound of metacarpophalangeal bone with double contour sign.
mediterranean journal 28
of RHEUMATOLOGY 2oi7
Figure 4: Patient 2. Ultrasound of knee cartilage with double contour sign.
Figure 5: Patient 2. Metacarpophalangeal bone tophus.
knees, wrists, elbows); receiving medium glucocortico-steroid doses (20-24 mg Medrol) with no improvement. No higher steroid dose was used because of difficult to control insulin dependent diabetes. His left wrist ultrasound revealed grade 3 tenosynovitis with the presence of echogenic elements within the sheath in the 4th dorsal compartment (common extensor of the fingers) with possible diagnosis of gout. Ultrasound of the right knee revealed a huge joint effusion, thickened synovium with increased vascularization within the joint and the supra-patellar recess as a grade 2, power Doppler, synovitis. The double contour sign was detected over the femoral condyles cartilage suggestive of gouty disease. It also revealed chordrocalcinosis. Synovial fluid examination was positive for MSU and CPPD crystals. Because of his resistant gouty disease and the limited therapeutic options, he received Canakinumab every 3 months with complete
resolution of his symptoms.
The fourth patient, 75 years old, suffers from neglected gouty disease for 20 years. He has extended presence of tophi in elbows, ankles, proximal and distal interpha-langeal joints. In the last 12 months, before the initialization of Canakinumab, he had five flares of gouty arthritis localized in wrists, metacarpophalangeal and distal in-terphalangeal joints. He was hospitalized twice. He received treatment with NSAIDS, glucocorticosteroids (0,5 mg/kg according to the ACR 2012 guidelines), colchicine with limited response and rapid symptom reappearance after medication withdrawal. He received Canakinumab every 3 months with remission of the flares and extended free of symptoms periods.
Experience with use of Canakinumab in patients with resistant gouty disease or with comorbidities which do not allow the use of common medication seems promising so far. International studies have positive results, showing that Canakinumab 150 mg offers quick and continuing relief from pain and significantly reduces the danger of flares comparing to conventional treatment.12 The 3-year follow up from two phase III studies revealed the effectiveness and the high safety profile of administrating Canakinumab to patients with difficult to treat gouty dis-ease.14. With the addition of new cases, better conclusions will arise for the use of Canakinumab in gout.
CONFLICT OF INTEREST
The authors declare no conflict of interest.
REFERENCES
1. Qing Y, Zhang Q, Zhou J. Innate immunity functional gen polymorphisms and gout susceptibility. Gene 2013;524:412-4.
2. Martinon F. Mechanisms of uric acid crystal mediated autoinflammation. Immunol Rev 2010;233.1:218-32.
3. Saag K G, Choi H. Epidemiology, risk factors, and lifestyle modifications for gout. Arthritis Res Ther 2006;8:S2.
4. Luk A J, Simkin P A. Epidemiology of Hyperuricemia and Gout. Am J Manag Care 2005;11:S435-S442.
5. Keenan R, O'Brien W, Lee K. Prevalence of contraindications and prescription of pharmacologic therapies for gout. Am J Med 2011;124,155-63.
6. Suresh E. Diagnosis and management of gout: a rational approach. Postgrad Med J 2005;81:572-9.
7. Latourte A, Bardin T, Richette P. Prophylaxis for acute gout flares after initiation of urate-lowering therapy. Rheumatology 2014;53:1920-6.
8. Cavalli G, Dinarello C. Treating rheumatological diseases and co-morbidities with interleukin-1 blocking therapies. Rheumatology 2015;54:2134-44.
9. Schlesinger N, Alten R, Brdin T. Canakinumab for acute gouty arthritis in patients with limited treatment options: results from two randomized, multicenter, active-controlled, double-blind trials and their initial extensions. Ann Rheum Dis 2012;71:1839-48.
10. Schlesinger N. Treatment of Acute Gout. Rheum Dis Clin N Am 2014;329-41.
11. Dumusc A, So A. Interleukin-1 as a therapeutic target in gout. Curr Opin Rheumatol 2015;27:156-63.
12. Hirch D, Gnanasakthy A, Lale R, Choi K, Sarkin A.J. Efficacy of canakinumab vs. triamcinolone acetonide according to multiple
THE USE OF CANAKINUMAB IN TREATING RESISTANT GOUTY DISEASE IN PATIENTS WITH LIMITED THERAPEUTIC OPTIONS: THE EXPERIENCE OF THE RHEUMATOLOGY CLINIC OF ASKLIPEION GENERAL HOSPITAL OF VOULA, GREECE
gouty Arthritis-related health outcomes measures. Int J Clin Pract 2014;68:1503-7.
13. So A, de Meulemeester M. Canakinumab for the Treatment of Acute Flares in Difficult-to-treat Gouty Arthritis. Arthritis Rheum 2010;62:3064-76.
14. Alten R, Bardin T, Bloch M, Lheriter K, Machein U, Junge G, et al. FRIO330 Safety and Efficacy of Canakinumab in Frequently Flaring Gouty Arthritis Patients Who are Contraindicated, Intolerant or Unresponsive to Non-Steroidal Anti-Inflammatory Drugs and/or Colchicine: Results from 3 Years Follow-Up. Ann Rheum Dis 2015;74:544. https://doi.org/10.1136/annrheumdis-2015-eu-lar.2199.
