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RESULTS OF USTEKINUMAB TREATMENT IN PATIENTS WITH PSORIATIC ARTHRITIS IN THE RUSSIAN FEDERATION ACCORDING TO THE DATA OF PSUMMIT 1 AND PSUMMIT 2

https://doi.org/10.14412/1995-4484-2015-125-133

Abstract

Psoriatic arthritis (PsA) is a chronic inflammatory disease of the joints, vertebral column,  and entesises, which is associated with psoriasis. T helper type 17 cells (Th-17)  play a leading role in the development of inflammation in psoriasis and PsA so different biologicals affecting interleukins (IL) 17 and 23 are being intensively investigated. Randomized, placebo-controlled Phase III PSUMMIT 1 (NCT01009086,  EudraCT  2009-012264-14) and PSUMMIT 2 (NCT01077362,  EudraCT  2009-012265-60) studies were undertaken  to evaluate the efficiency and tolerability of  ustekinumab  (UST) treatment in PsA patients.

Subjects and methods. The PSUMMIT 1 study covered 152 Russian patients with active PsA (≥5 tender and ≥5 swollen joints; C-reactive protein ≥3 mg/l) who were randomly (using the dynamic centralized randomization method on the basis of an interactive vocal response algorithm) divided into three groups (at a 1:1:1 ratio): 1) subcutaneous UST 45 mg; 2) UST 90 mg; 3) placebo (PL) at baseline, 4 weeks later, and then every 12 weeks). After 16 weeks the patients showing a less than 5% reduction  in the number of tender and swollen joints were given UST 45 mg (if they belonged to the PL group) or 90 mg (if they were in the UST 45-mg group). The PL-receiving patients were given UST 45 mg at weeks 24 and 28 and then every 12 weeks. The treatment duration was 2 years. A therapeutic  response  was estimated by theAmericanCollege of Rheumatology (ACR) response criteria. The PSUMMIT 2 study enrolled 40 Russian patients who had previously received or were currently receiving disease-modifying anti-rheumatic drugs and/or nonsteroidal  anti-inflammatory drugs and tumor necrosis factor-α  inhibitors. The patients were randomized  to the groups of those receiving UST 45 mg or 90 mg or PL at baseline and at week 4, then once every 12 weeks. The last dose of UST was given at week 40. The follow-up lasted until week 60.

Results and discussion. In the PSUMMIT 1 study, 24-week administration of UST 45 mg and 90 mg significantly more frequently ensured a 20% improvement according to the ACR criteria than that of PL (39.2; 44.0, and 15.7%, respectively; p < 0.01); the therapeutic response persisted until week52. In the PSUMMIT 2, following 24 weeks, the UST 45-mg and 90-mg groups considerably more often showed a 20% improvement according to the ACR criteria than the PL group (64.3, 57.1, and 16.7%, respectively; p < 0.01); the therapeutic response persisted until week 52. Among 150 Russian patients taking UST, on the average, for 45.1 weeks in the PSUMMIT 1 study, 62 (41.3%) were observed to have adverse events (AE) that were serious in 6 (4.0%). Among 40 PsA patients who participated  in the PSUMMIT 2 study inRussia, AEs were seen in a total of 25 (62.5%) patients, serious AEs being absent.

Conclusion. The results of the PSUMMIT 1 and PSUMMIT studies in the Russian population  indicated that UST treatment contributed  to a significant reduction  of PS symptoms and exhibited a good tolerability.

DOI: http://dx.doi.org/10.14412/1995-4484-2015-125-133

About the Authors

Yu. L. Korsakova
V.A. Nasonova Research Institute of Rheumatology, Moscow
Russian Federation

Competing Interests:

Contact: Yulia Korsakova;   yulkorsakova@bk.ru



A. A. Godzenko
Russian Medical Academy of Postgraduate Education, Moscow
Russian Federation

Competing Interests: Department of Rheumatology


A. O. Pchelintseva
V.A. Nasonova Research Institute of Rheumatology, Moscow
Russian Federation

Competing Interests: Научно-исследовательский институт ревматологии им. В.А. Насоновой, Москва


O. Yu. Grigoryeva
Johnson & Johnson’s Janssen Pharmaceuticals
Russian Federation


L. N. Denisov
V.A. Nasonova Research Institute of Rheumatology, Moscow
Russian Federation


E. L. Nasonov
V.A. Nasonova Research Institute of Rheumatology, Moscow
Russian Federation


References

1. Yeremenko N, Paramarta JE, Baeten D. The interleukin-23/interleukin-17 immune axis as a promising new target in the treatment of spondyloarthritis. Curr Opin Rheumatol. 2014 Jul;26(4):361–70. doi: 10.1097/BOR.0000000000000069

2. Leonardi CL, Matheson R, Zachariae C, et al. Antiinterleukin-17 monoclonal antibody ixekizumab in chronic plaque psoriasis. N Engl J Med. 2012;366:1190–9. doi: 10.1056/NEJMoa1109997

3. Papp KA, Leonardi C, Menter A, et al. Brodalumab, an antiinterleukin-17-receptor antibody for psoriasis. N Engl J Med. 2012;366:1181–9. doi: 10.1056/NEJMoa1109017

4. Leonardi CL, Kimball AB, Papp KA, et al, for the PHOENIX1 study investigators. Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 76-week results from a randomised, double-blind, placebo-controlled trial (PHOENIX 1). Lancet. 2008;371:1665–74. doi: 10.1016/S0140-6736(08)60725-4

5. Papp KA, Langley RG, Lebwohl M, et al. Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 52-week results from a randomised, double-blind, placebo-controlled trial (PHOENIX 2). Lancet. 2008;371:1675–84. doi: 10.1016/S0140-6736(08)60726-6

6. Griffiths CEM, Strober BE, van de Kerkhof P, et al. Comparison of ustekinumab and etanercept for moderate-to-severe psoriasis. N Engl J Med. 2010;362:118–28. doi: 10.1056/NEJMoa0810652

7. Gottlieb A, Menter A, Mendelsohn A, et al. Ustekinumab, a human interleukin 12/23 monoclonal antibody, for psoriatic arthritis: randomised, double-blind, placebo-controlled, crossover trial. Lancet. 2009;373:633–40. doi: 10.1016/S0140-6736(09)60140-9

8. McInnes IB, Kavanaugh A, Gottlieb AB, et al. Efficacy and safety of ustekinumab in patients with active psoriatic arthritis: 1 year results of the phase 3, multicentre, double-blind, placebo-controlled PSUMMIT 1 trial. Lancet. 2013 Aug 31;382(9894):780–9. doi: 10.1016/S0140-6736(13)60594-2. Epub 2013 Jun 13.

9. Ritchlin C, Rahman P, Kavanaugh A, et al. Efficacy and safety of the anti-IL-12/23 p40 monoclonal antibody, ustekinumab, in patients with active psoriatic arthritis despite conventional non-biological and biological anti-tumour necrosis factor therapy: 6-month and 1-year results of the phase 3, multicentre, double-blind, placebo-controlled, randomised PSUMMIT 2 trial. Ann Rheum Dis. 2014 Jun;73(6):990–9. doi: 10.1136/annrheumdis-2013-204655

10. Fries JF, Spitz P, Kraines RG, Holman HR. Measurement of patient outcome in arthritis. Arthritis Rheum. 1980;23:137–45. doi: 10.1002/art.1780230202

11. Garrett S, Jenkinson T, Kennedy LG, et al. A new approach to defining disease status in ankylosing spondylitis: the Bath ankylosing spondylitis disease activity index. J Rheumatol. 1994;21:2286–91.

12. Conover WJ. Practical nonparametric statistics. 2nd ed. New York: John Wiley & Sons; 1980.

13. Celis R, Planell N, Fernandez-Sueiro JL, et al. Synovial cytokine expression in psoriatic arthritis and associations with lymphoid neogenesis and clinical features. Arthritis Res Ther. 2012;14:R93. doi: 10.1186/ar3817

14. Kavanaugh A, Ritchlin C, Rahman P, et al.; on behalf of the PSUMMIT-1 and -2 Study Groups. Ustekinumab, an anti-IL-12/23 p40 monoclonal antibody, inhibits radiographic progression in patients with active psoriatic arthritis: results of an integrated analysis of radiographic data from the Phase 3, multicentre, randomised, double-blind, placebo-controlled PSUMMIT-1 and PSUMMIT-2 trials. Ann Rheum Dis. 2014;73(6):1000–6. doi: 10.1136/annrheumdis-2013-204741

15. Krausz S, Boumans MJH, Gerlag DM, et al. A phase IIa, randomized, double-blind, placebo-controlled trial of apilimodmesylate, an interleukin-12/interleukin-23 inhibitor, in patients with rheumatoid arthritis. Arthritis Rheum. 2012;64:1750–5. doi: 10.1002/art.34339

16. Toichi E, Torres G, McCormick TS, et al. An anti-IL-12p40 antibody down-regulates type 1 cytokines, chemokines, and IL-12/IL-23 in psoriasis. J Immunol. 2006;177:4917–26. doi: 10.4049/jimmunol.177.7.4917

17. Reich K, Papp KA, Griffiths CE, et al. An update on the longterm safety experience of ustekinumab: results from the psoriasis clinical development program with up to four years of follow-up. J Drugs Dermatol. 2012;11:300–12.


Review

For citations:


Korsakova Yu.L., Godzenko A.A., Pchelintseva A.O., Grigoryeva O.Yu., Denisov L.N., Nasonov E.L. RESULTS OF USTEKINUMAB TREATMENT IN PATIENTS WITH PSORIATIC ARTHRITIS IN THE RUSSIAN FEDERATION ACCORDING TO THE DATA OF PSUMMIT 1 AND PSUMMIT 2. Rheumatology Science and Practice. 2015;53(2):125-133. (In Russ.) https://doi.org/10.14412/1995-4484-2015-125-133

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ISSN 1995-4484 (Print)
ISSN 1995-4492 (Online)