The Efficacy of Infliximab Plus Methotrexate in Patients with Active Rheumatoid Arthritis in North of Iraq: 5 year Extended Study

Niaz Jawad  Albarzinji

doi:10.56056/amj.2018.33

Authors

Niaz Jawad Albarzinji Hawler Medical University/ College of Medicine

DOI:

https://doi.org/10.56056/amj.2018.33

Keywords:

Infleximab, Methotroxate, Rheumatoid Arthritis

Abstract

Background and objectives: Anti-Tumor necrosis factor agents are among the most effective therapies for Rheumatoid Arthritis, however, their optimal use is yet to be determined.In this 5 year open-labeled study attempted remission induction using standard therapy with infliximab in patients with poor response to ordinary disease modifying anti-Rheumatic drugs.

Methods: Patients responding inadequately to methotrexate and at least one other disease-modi- fying anti-rheumatic drug were enrolled into a 24-week, controlled study with infliximab plus methotrexate or placebo plus methotrexate and some were enrolled in a subsequent open-label extension. The efficacy were evaluated by measuring the disease activity by using DAS-28(disease activity score in 28 points) and functional evaluation by using the health assessment questioner (HAQ).

Results: Among 250 patients in the original trial, 220 received at least one dose of infliximab and were evaluated. At the time of analysis 160/ 220 (72.7%) patients had remained in the study and received treatment for a mean of 4.5 years. Withdrawals were for lack of efficacy (24%), adverse events (36%), and other reasons (50%). In 160 patients who completed 5 years treatment efficacy achieved in 6 months was maintained at 5 years. 45% achieved clinical remission (DAS28<2.6), and 27% had no physical function abnormalities (HAQ=0). Results were similar for 160 patients who received treatment for 3-5 years.

Conclusions: In patients with persistently active Rheumatoid Arthritis despite Methotraxate therapy, repeated doses of infliximab in combination with methotraxate provided clinical remissions with functional and quality of life benefits were sustained.

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References

Choy E, Panayi G. Cytokine pathways and joint inflammation in rheumatoid arthritis. N Engl J Med 2001; 344:907-16.

Emery P, Salmon M. Early rheumatoid arthritis: time to aim for remission? Ann Rheum Dis 1995; 54: 944–7.

Quinn MA, Conaghan PG, Emery P. The therapeutic approach of early intervention for rheumatoid arthritis: what is the evidence? Rheumatol- ogy (Oxford) 2001; 40: 1211–20.

Emery P. Prognosis in inflammatory arthritis: the value of HLA genotyping and oncological analogy. J Rheumatol 1997; 24: 1436–42.

Boers M. Understanding the window of opportunity concept in early rheumatoid arthritis [review]. Arthritis Rheum 2003; 48: 1771–4.

Quinn MA, Emery P. Window of opportunity in early rheumatoid ar- thritis: possibility of altering the disease process with early intervention. Clin Exp Rheumatol 2003; 21 Suppl 31: S154–7.

Lipsky P, van der Heijde DM, St. Clair EW, Furst DE, Breedveld FC, Kalden JR, et al. Infliximab and methotrexate in the treatment of rheumatoid arthritis: anti-tumor necrosis factor trial in rheumatoid arthritis with concomitant therapy study group. N Engl J Med 2000; 343: 1594–602.

Baert FJ, d’Haens GR, Peeters M, Hiele MI, Schaible TF, Shealy D, et al. Tumor necrosis factor ? antibody (infliximab) therapy profoundly down-regulates the inflammation in Crohn’s ileocolitis. Gastroenterolo- gy 1999; 116: 22–8.

Braun J, Brandt J, Listing J, Zink A, Alten R, Golder W, et al. Treatment of active ankylosing spondylitis with infliximab: a randomised controlled multicentre trial. Lancet 2002; 359: 1187–93.

Mease PJ, Goffe BS, Metz J, VanderStoep A, Finck B, Burge DJ. Etanercept in the treatment of psoriatic arthritis and psoriasis: a randomized trial. Lancet 2000; 356: 385–90.

Present DH, Rutgeerts P, Targan S, Hanauer SG, Mayer L, van Hogezand RA, et al. Infliximab for the treatment of fistulas in patients with Crohn’s disease. N Engl J Med 1999; 340: 1398–405.

Buch M, Marzo-Ortega H, Bingham SJ, Lindsay S, Emery P. What happens when infliximab is stopped after two years exposure in patients with RA? Time taken to flare and efficacy on reintroduction of infliximab. Rheumatology (Oxford) 2004; 43: 243–4.

Arnett F, Edwarthy S, Bloch D, 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.

Prevoo M, van T Hof M, Kuper H, van Leeuwent, M, van de Putte L, Riel P. Modified disease activity scores that include twenty-eight-joint counts. Arthritis Rheum 1995;38:44-8.

Prevoo M, van T Hof M, van Gestel A, van Rijiswik M, van de Putte L, Riel P. Remission in a prospective study of patients with rheumatoid arthritis. American Rheumatism Association preliminary remission criteria in relation to the disease activity score. Br J Rheumatolo 1996;35:1101-5.

Kremer J, Weinblatt M, Bankhurst A, Bulpitt KJ, Fleischmann RM, Jackson CG, et al. Etanercept added to background methotrexate therapy in patients with rheumatoid arthritis. Continued observation. Arthritis Rheum 2003;6;1493-9.

Weinblatt M. Rheumatoid arthritis in 2003: where are we now with treatment? Ann Rheum Dis 2003;63(suppl 2): 1194-6.

Wolfe F, Rehman Q, Lane N, Kremer J. Starting a disease-modifying antirheumatic drug or a biologic agent in rheumatoid arthritis: standards of practice for RA treatment. J Rheumatol 2001;28:1704-11

Lambert C, Sandhu S, Lachhead A, Hurst NP, McRorie E, Dhillon V. Dose escalation of parenteral methotrexate in active rheumatoid arthritis that has been unresponsive to conventional doses of methotrexate. A randomized, controlled trial. Arthritis Rheum 2004;50:364-71.

O’Dell J, Haire C, Erikson N, Drymalski W, Palmer W, Eckhoff PJ, et al. Treatment of rheumatoid arthritis with methotrexate alone, sulasala- zine and hydroxychloroquine or a combination of all three medications. N Engl J Med 1996;334:1287-91.

Keystone E, Kavanaugh A, Sharp J, Tannenbaum H, Hua Y, Teoh LS, et al. Radiographic, clinical and functional outcomes of treatment with adalimimab ( a human anti-tumor necrosis factor monoclonal antibody). in patients with active rheumatoid arthritis receiving concomitant methotrexate therapy. Arthritis Rheum 2004;50:1400-11.

Maini R, Breeveld F, Kalden J, Smolen JS, Furst D, Weisman MH, et al. Sustained improvement over two years in physical function, structural damage and signs and symptoms among patients with rheumatoid arthritis treated with infliximab and methotrexate. Arthritis Rheum 2004;50:1051-65.

St Clair E, Desiree M, van der Heijda D, Maini RN, Bathon JM, Emery P, et al. Combination of infliximab and methotrexate therapy for early rheumatoid arthritis. Arthritis Rheum 2004;50:3432-43.

Weinblall M, Kremer J, Bankhurst A, Bulpitt KJ, Fleischmann RM, Fox RI, et al. A trial of etanercept, a recombinant tumor necrosis factor receptor Fc fusion protein, in patients with rheumatoid arthritis receiving methotrexate. N Engl J Med 1999;340:253-9.

Klareskog L, van der Heijda D, de Jager J, Gough A, Kalden A, 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 randomized controlled trial. Lancet 2004;363:675-81.

Genovese M, Bathon J, Martin R, Fleischmann RM, Tesser JR, Schiff MH, et al. Etanercept versus methotrexate in patients with early rheumatoid arthritis: two years radiographical and clinical outcomes. Arthritis Rheum 2002;46:1443-50.

Moreland LW, Cohen SB, Baumgartner SW, Tindall EA, Bulpitt K, Mar- tin R, et al. Long-term safety and efficacy of etanercept in patients with rheumatoid arthritis. J Rheumatol 2001;28:1238-44.

Felson DT, Edwarthy S, Bloch D, McShane DJ, Fries JF, Cooper NS, et al. American College of Rheumatology preliminary definition of improve- ment in rheumatoid arthritis. Arthritis Rheum 1995;38:727-35.

Lubeck D. Health-related quality of life measurements and studies in rheumatoid arthritis. Am J Manag Care 2002;8:811-20.

Surveillance, Epidemiology and End Results (SEER) Program Pub- lic-Use Data Program, Cancer Statistics Branch, released April 2002, based on the November 2001 submission.

Balsa A, Carmona L, Gonzalez-Alvaro I, Belmonte MA, Tena X, Sam- marti R. Value of disease Activity Score 28 (DAS28) and DAS28-3 compared to American College of Rheumatology-defined remission in rheumatoid arthritis. J Rheumatol 2004;31:40-6.

Goldsmith CH, Boers M, Bambardier C, Tugwell P. Criteria for clinically important changes in outcomes: development, scoring and evaluation of rheumatoid arthritis patient and trial profiles. OMERACT Committee. J Rheumatol 1993;20:561-5.

Breedveld F, Han C, Bala M, van der Heijda D, Baker D, Kavanaugh AF, et al. Association between baseline radiographic damage and improvement in physical function after treatment of patients with rheumatoid arthritis. Ann Rheum Dis 2005;64:52-5.

Doran M, Crowson C, Pond G, O’Fallon W, Gabriel S. Frequency of infection in patients with rheumatoid arthritis compared with controls: a population-based study. Arthritis Rheum 2002;46:2287-93.

Goekoop-Ruiterman YP, de Vries-Bouwstra JK, Allaart CF, van Ze- ben D, Kerstens PJ, Hazes JM, et al. Comparison of treatment strategies in early rheumatoid arthritis: a randomized trial. Ann Intern Med 2007; 146: 406–15.

Quinn MA, Emery P. Window of opportunity in early rheumatoid ar- thritis: possibility of altering the disease process with early intervention [review]. Clin Exp Rheumatol 2003; 21(5 Suppl 31 ): S154–7.

Quinn MA, Conaghan PG, O’Connor PJ, Karim Z, Greenstein A, Brown A, et al. Very early treatment with infliximab in addition to methotrexate in early, poor-prognosis rheumatoid arthritis reduces magnetic resonance imaging evidence of synovitis and damage, with sustained benefit after infliximab withdrawal: results from a twelve-month randomized, double-blind, placebo-controlled trial. Arthritis Rheum 2005; 52: 27–35.

Bongartz T, Sutton AJ, Sweeting MJ, Buchan I, Matteson EL, Montori V. Anti-TNF antibody therapy in rheumatoid arthritis and the risk of serious infections and malignancies: systematic review and meta-analysis of rare harmful effects in randomized controlled trials [published erratum appears in JAMA 2006;295:2482]. JAMA 2006; 295: 2275–85.