Sustained Response Following Discontinuation of Methotrexate in Patients With Rheumatoid Arthritis Treated With Subcutaneous Tocilizumab: Results From a Randomized, Controlled Trial

Arthritis and Rheumatology

Volumn 70, Issue 8, 2018, Pages 1200-1208

  Kremer, Joel M ^a   Rigby, William ^b   Singer, Nora G ^c   Birchwood, Christine ^d   Gill, Darcy ^d   Reiss, William ^d   Pei, Jinglan ^d   Michalska, Margaret ^d  

^a ALBANY MEDICAL COLLEGE   (United States)

^b DARTMOUTH COLLEGE   (United States)

^c CASE WESTERN RESERVE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^d GENENTECH INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ABATACEPT; ANAKINRA; CORTICOSTEROID; IMMUNOGLOBULIN; METHOTREXATE; RITUXIMAB; TOCILIZUMAB; TOFACITINIB; ANTIRHEUMATIC AGENT; MONOCLONAL ANTIBODY;

ADULT; ARTICLE; CLINICAL OUTCOME; CONTROLLED STUDY; CORTICOSTEROID THERAPY; DAS28; DOUBLE BLIND PROCEDURE; DRUG WITHDRAWAL; ERYTHROCYTE SEDIMENTATION RATE; FEMALE; HUMAN; MAJOR CLINICAL STUDY; MALE; MONOTHERAPY; MULTICENTER STUDY; PARALLEL DESIGN; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; RHEUMATOID ARTHRITIS; TREATMENT DURATION; CLINICAL TRIAL; COMBINATION DRUG THERAPY; DISEASE EXACERBATION; MIDDLE AGED; PATHOLOGY; TIME FACTOR; TREATMENT OUTCOME; TREATMENT WITHDRAWAL;

ADULT; ANTIBODIES, MONOCLONAL, HUMANIZED; ANTIRHEUMATIC AGENTS; ARTHRITIS, RHEUMATOID; DISEASE PROGRESSION; DOUBLE-BLIND METHOD; DRUG THERAPY, COMBINATION; FEMALE; HUMANS; MALE; METHOTREXATE; MIDDLE AGED; TIME FACTORS; TREATMENT OUTCOME; WITHHOLDING TREATMENT;

EID: 85050639107     PISSN: 23265191     EISSN: 23265205     Source Type: Journal    
DOI: 10.1002/art.40493     Document Type: Article

References (40)

1. Smolen JS, Beaulieu A, Rubbert-Roth A, Ramos-Remus C, Rovensky J, Alecock E, et al. Effect of interleukin-6 receptor inhibition with tocilizumab in patients with rheumatoid arthritis (OPTION study): a double-blind, placebo-controlled, randomised trial. Lancet 2008;371:987–97.
2. Genovese MC, McKay JD, Nasonov EL, Mysler EF, da Silva NA, Alecock E, et al. Interleukin-6 receptor inhibition with tocilizumab reduces disease activity in rheumatoid arthritis with inadequate response to disease-modifying antirheumatic drugs: the Tocilizumab in Combination with Traditional Disease-Modifying Antirheumatic Drug Therapy study. Arthritis Rheum 2008;58:2968–80.
3. Emery P, Keystone E, Tony HP, Cantagrel A, van Vollenhoven R, Sanchez A, et al. IL-6 receptor inhibition with tocilizumab improves treatment outcomes in patients with rheumatoid arthritis refractory to anti-tumour necrosis factor biologicals: results from a 24-week multicentre randomised placebo-controlled trial. Ann Rheum Dis 2008;67:1516–23.
4. Jones G, Sebba A, Gu J, Lowenstein MB, Calvo A, Gomez-Reino JJ, et al. Comparison of tocilizumab monotherapy versus methotrexate monotherapy in patients with moderate to severe rheumatoid arthritis: the AMBITION study. Ann Rheum Dis 2010;69:88–96.
5. Kremer JM, Blanco R, Brzosko M, Burgos-Vargas R, Halland AM, Vernon E, et al. Tocilizumab inhibits structural joint damage in rheumatoid arthritis patients with inadequate responses to methotrexate: results from the double-blind treatment phase of a randomized placebo-controlled trial of tocilizumab safety and prevention of structural joint damage at one year. Arthritis Rheum 2011;63:609–21.
6. De Benedetti F, Brunner HI, Ruperto N, Kenwright A, Wright S, Calvo I, et al. Randomized trial of tocilizumab in systemic juvenile idiopathic arthritis. N Engl J Med 2012;367:2385–95.
7. Brunner HI, Ruperto N, Zuber Z, Keane C, Harari O, Kenwright A, et al. Efficacy and safety of tocilizumab in patients with polyarticular-course juvenile idiopathic arthritis: results from a phase 3, randomised, double-blind withdrawal trial. Ann Rheum Dis 2015;74:1110–7.
8. Burmester GR, Rubbert-Roth A, Cantagrel A, Hall S, Leszczynski P, Feldman D, et al. A randomised, double-blind, parallel-group study of the safety and efficacy of subcutaneous tocilizumab versus intravenous tocilizumab in combination with traditional disease-modifying antirheumatic drugs in patients with moderate to severe rheumatoid arthritis (SUMMACTA study). Ann Rheum Dis 2014;73:69–74.
9. Kivitz A, Olech E, Borofsky M, Zazueta BM, Navarro-Sarabia F, Radominski SC, et al. Subcutaneous tocilizumab versus placebo in combination with disease-modifying antirheumatic drugs in patients with rheumatoid arthritis. Arthritis Care Res (Hoboken) 2014;66:1653–61.
10. Stone JH, Tuckwell K, Dimonaco S, Klearman M, Aringer M, Blockmans D, et al. Trial of tocilizumab in giant-cell arteritis. N Engl J Med 2017;377:317–28.
11. Breedveld FC, Weisman MH, Kavanaugh AF, Cohen SB, Pavelka K, van Vollenhoven R, et al. The PREMIER study: a multicenter, randomized, double-blind clinical trial of combination therapy with adalimumab plus methotrexate versus methotrexate alone or adalimumab alone in patients with early, aggressive rheumatoid arthritis who had not had previous methotrexate treatment. Arthritis Rheum 2006;54:26–37.
12. Klareskog L, van der Heijde D, de Jager JP, Gough A, Kalden J, Malaise M, et al. Therapeutic effect of the combination of etanercept and methotrexate compared with each treatment alone in patients with rheumatoid arthritis: double-blind randomised controlled trial. Lancet 2004;363:675–81.
13. Gabay C, Emery P, van Vollenhoven R, Dikranian A, Alten R, Pavelka K, et al. Tocilizumab monotherapy versus adalimumab monotherapy for treatment of rheumatoid arthritis (ADACTA): a randomised, double-blind, controlled phase 4 trial. Lancet 2013;381:1541–50.
14. Dougados M, Kissel K, Sheeran T, Tak PP, Conaghan PG, Mola EM, et al. Adding tocilizumab or switching to tocilizumab monotherapy in methotrexate inadequate responders: 24-week symptomatic and structural results of a 2-year randomised controlled strategy trial in rheumatoid arthritis (ACT-RAY). Ann Rheum Dis 2013;72:43–50.
15. Dougados M, Kissel K, Conaghan PG, Mola EM, Schett G, Gerli R, et al. Clinical, radiographic and immunogenic effects after 1 year of tocilizumab-based treatment strategies in rheumatoid arthritis: the ACT-RAY study. Ann Rheum Dis 2014;73:803–9.
16. Ogata A, Tanimura K, Sugimoto T, Inoue H, Urata Y, Matsubara T, et al. Phase III study of the efficacy and safety of subcutaneous versus intravenous tocilizumab monotherapy in patients with rheumatoid arthritis. Arthritis Care Res (Hoboken) 2014;66:344–54.
17. Listing J, Strangfeld A, Rau R, Kekow J, Gromnica-Ihle E, Klopsch T, et al. Clinical and functional remission: even though biologics are superior to conventional DMARDs overall success rates remain low: results from RABBIT, the German Biologics Register. Arthritis Res Ther 2006;8:R66.
18. Soliman MM, Ashcroft DM, Watson KD, Lunt M, Symmons DP, Hyrich KL, et al. Impact of concomitant use of DMARDs on the persistence with anti-TNF therapies in patients with rheumatoid arthritis: results from the British Society for Rheumatology Biologics Register. Ann Rheum Dis 2011;70:583–9.
19. Felson DT, Smolen JS, Wells G, Zhang B, van Tuyl LH, Funovits J, et al. American College of Rheumatology/European League Against Rheumatism provisional definition of remission in rheumatoid arthritis for clinical trials. Arthritis Rheum 2011;63:573–86.
20. Furst DE, Koehnke R, Burmeister LF, Kohler J, Cargill I. Increasing methotrexate effect with increasing dose in the treatment of resistant rheumatoid arthritis. J Rheumatol 1989;16:313–20.
21. Schnabel A, Reinhold-Keller E, Willmann V, Gross WL. Tolerability of methotrexate starting with 15 or 25 mg/week for rheumatoid arthritis. Rheumatol Int 1994;14:33–8.
22. Verstappen SM, Jacobs JW, van der Veen MJ, Heurkens AH, Schenk Y, ter Borg EJ, et al. Intensive treatment with methotrexate in early rheumatoid arthritis: aiming for remission. Computer Assisted Management in Early Rheumatoid Arthritis (CAMERA, an open-label strategy trial). Ann Rheum Dis 2007;66:1443–9.
23. Prevoo ML, van ‘t Hof MA, Kuper HH, van Leeuwen MA, van de Putte LB, van Riel PL. Modified disease activity scores that include twenty-eight–joint counts: development and validation in a prospective longitudinal study of patients with rheumatoid arthritis. Arthritis Rheum 1995;38:44–8.
24. Felson DT, Anderson JJ, Boers M, Bombardier C, Furst D, Goldsmith C, et al. American College of Rheumatology preliminary definition of improvement in rheumatoid arthritis. Arthritis Rheum 1995;38:727–35.
25. Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS, et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 1988;31:315–24.
26. Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, Bingham CO III, et al. 2010 rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum 2010;62:2560–81.
27. Fransen J, van Riel PL. The disease activity score and the EULAR response criteria. Clin Exp Rheumatol 2005;23:S93–9.
28. Aletaha D, Nell VP, Stamm T, Uffmann M, Pflugbeil S, Machold K, et al. Acute phase reactants add little to composite disease activity indices for rheumatoid arthritis: validation of a clinical activity score. Arthritis Res Ther 2005;7:R796–806.
29. Burmester GR, Kivitz AJ, Kupper H, Arulmani U, Florentinus S, Goss SL, et al. Efficacy and safety of ascending methotrexate dose in combination with adalimumab: the randomised CONCERTO trial. Ann Rheum Dis 2015;74:1037–44.
30. Kaeley GS, Evangelisto AM, Nishio MJ, Goss SL, Liu S, Kalabic J, et al. Methotrexate dosage reduction upon adalimumab initiation: clinical and ultrasonographic outcomes from the randomized noninferiority MUSICA trial. J Rheumatol 2016;43:1480–9.
31. Pope JE, Haraoui B, Thorne JC, Vieira A, Poulin-Costello M, Keystone EC. The Canadian methotrexate and etanercept outcome study: a randomised trial of discontinuing versus continuing methotrexate after 6 months of etanercept and methotrexate therapy in rheumatoid arthritis. Ann Rheum Dis 2014;73:2144–51.
32. Dervieux T, Weinblatt ME, Kivitz A, Kremer JM. Methotrexate polyglutamation in relation to infliximab pharmacokinetics in rheumatoid arthritis. Ann Rheum Dis 2013;72:908–10.
33. Bartelds GM, Krieckaert CL, Nurmohamed MT, van Schouwenburg PA, Lems WF, Twisk JW, et al. Development of antidrug antibodies against adalimumab and association with disease activity and treatment failure during long-term follow-up. JAMA 2011;305:1460–8.
34. Krintel SB, Grunert VP, Hetland ML, Johansen JS, Rothfuss M, Palermo G, et al. The frequency of anti-infliximab antibodies in patients with rheumatoid arthritis treated in routine care and the associations with adverse drug reactions and treatment failure. Rheumatology (Oxford) 2013;52:1245–53.
35. Burmester GR, Choy E, Kivitz A, Ogata A, Bao M, Nomura A, et al. Low immunogenicity of tocilizumab in patients with rheumatoid arthritis. Ann Rheum Dis 2017;76:1078–85.
36. Kremer JM, Lawrence DA, Hamilton R, McInnes IB. Long-term study of the impact of methotrexate on serum cytokines and lymphocyte subsets in patients with active rheumatoid arthritis: correlation with pharmacokinetic measures. RMD Open 2016;2:e000287.
37. Kremer JM, Rynes RI, Bartholomew LE. Severe flare of rheumatoid arthritis after discontinuation of long-term methotrexate therapy: double-blind study. Am J Med 1987;82:781–6.
38. Kremer JM, Davies JM, Rynes RI, Fink S, Lawrence DA, Petrillo GF, et al. Every-other-week methotrexate in patients with rheumatoid arthritis: a double-blind, placebo-controlled prospective study. Arthritis Rheum 1995;38:601–7.
39. Catay E, Bravo M, Rosa J, Soriano ER. Prevalence of biologics monotherapy in a cohort of patients with rheumatoid arthritis in daily clinical practice. BMC Musculoskelet Disord 2016;17:110.
40. Mariette X, Gottenberg JE, Ravaud P, Combe B. Registries in rheumatoid arthritis and autoimmune diseases: data from the French registries. Rheumatology (Oxford) 2011;50:222–9.