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Assessment of the treat-to-target strategy in patients with refractory rheumatoid arthritis

A prospective study on efficacy and safety in a Saudi population

Untersuchung der zielgenauen Behandlungsstrategie bei Patienten mit therapierefraktärer rheumatoider Arthritis

Eine prospektive Studie zur Wirksamkeit und Sicherheit in einer saudischen Population

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Abstract

Aim

The goal of the present study was to prospectively assess the long-term clinical outcome of biologic modifying drug therapy in a population of Saudi rheumatoid arthritis (RA) patients.

Patients and methods

This is the first prospective, long-term report on the efficacy and safety of biologic therapy in Saudi RA patients. It is a single center, observational study with a follow-up period of 3 years. Enrolled were 120 biologic naïve patients (94 women, 78.3 %; mean age 48.4 ± 17.9 years, mean disease duration 7.3 ± 3.9 years) with the diagnosis of RA (ACR/EULAR, 2010 criteria) who were inadequate responders to methotrexate and synthetic DMARDs.

Results

After 3 years, the mean Disease Activity Index-28 (DAS-28), Health Assessment Questionnaire (HAQ), Pain Score, ESR, and CRP values improved significantly. Of the 99 patients completing the 3-year follow-up, 35.3 % of patients achieved DAS-28 remission and 53.5 % achieved low disease activity, and 11.1 % of patients had moderate to high activity scores. At the 3-year follow-up, 80 % of patients had no evidence of significant radiographic progression (achieved < 0.5 of the mean total Sharp score). Infections were reported in 11.7 % and significantly correlated with conjugate use of oral prednisolone at doses above 5 mg/day, with chest infections being the most common type of infection (6.7 %).

Conclusion

The results of this study can be understood as real-life clinical experience displaying the incremental benefit of biologic therapy in refractory disease when it is added to other optimal strategies. The study showed satisfying clinical and functional benefit with considerable safety.

Zusammenfassung

Ziel

Ziel der vorliegenden Studie war die prospektive Untersuchung des klinischen Langzeitverlaufs unter biologischer krankheitsmodifizierender medikamentöser Therapie in einer Population von saudischen Patienten mit rheumatoider Arthritis (RA).

Patienten und Methoden

Dies ist die erste prospektive Langzeitstudie zur Wirksamkeit und Sicherheit der biologischen Therapie bei saudischen RA-Patienten. Es handelt sich um eine Einzelzentrum-Beobachtungsstudie über 3 Jahre. In die Studie eingeschlossen wurden 120 Biologika-naive Patienten (94 Frauen, 78,3 %; Durchschnittsalter: 48,4 ± 17,9 Jahre, durchschnittliche Krankheitsdauer: 7,3 ± 3,9 Jahre) mit der Diagnose einer RA (ACR/EULAR-Kriterien von 2010), die nicht ausreichend auf Methotrexat und synthetische DMARD ansprachen.

Ergebnisse

Nach 3 Jahren besserten sich die Durchschnittswerte für den Disease Activity Score 28 (DAS-28), Health Assessment Questionnaire, Schmerzscore, BSG und CRP deutlich. Beim DAS-28 erzielten von den 99 Patienten mit vollständiger 3-jähriger Nachbeobachtung 35,3 % eine Remission, 53,5 % eine niedrige Krankheitsaktivität und 11,1 % einen mittleren bis hohen Wert. Nach 3 Jahren Follow-up bestand bei 80 % der Patienten kein Hinweis auf eine wesentliche röntgenologische Progression (< 0,5 des durchschnittlichen Sharp-Gesamtscores). Infektionen wurden in 11,7 % der Fälle dokumentiert, sie waren signifikant mit der kombinierten Gabe von Prednisolon p.o. in Dosen über 5 mg/ korreliert, am häufigsten (6,7 %) waren Thoraxinfektionen.

Schlussfolgerung

Die Ergebnisse der vorliegenden Studie können als praktische klinische Erfahrung angesehen werden, welche den zunehmenden Nutzen der biologischen Therapie bei therapierefraktärer Erkrankung zeigt, wenn sie optimal mit anderen Strategien zusammen eingesetzt wird; die Studie ergab einen befriedigenden klinischen und funktionellen Nutzen bei beträchtlicher Sicherheit.

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References

  1. Burmester G-R, Pratt AG, Scherer HU, Van-Laar JM (2012) Rheumatoid arthritis: pathogenesis and clinical features. In: Bijlsma JWJ (ed) EULAR textbook on rheumatic diseases. 1st edn., BMJ Publications, London. Chapter 9. pp 206–231

  2. Wolfe F, Michaud K (2010) The loss of health status in rheumatoid arthritis and the effect of biologic therapy: a longitudinal observational study. Arthritis Res Ther 12:R35

    Article  PubMed  PubMed Central  Google Scholar 

  3. Gaujoux-Viala C, Smolen JS, Landewé R et al (2010) Current evidence for the management of rheumatoid arthritis with synthetic disease-modifying anti-rheumatic drugs: systematic literature review informing the EULAR recommendations for the management of rheumatoid arthritis. Ann Rheum Dis 69:1004–1009

    Article  PubMed  CAS  Google Scholar 

  4. Scott DL, Kingsley GH (2006) Tumor necrosis factor inhibitors for rheumatoid arthritis. N Engl J Med 355:704–712

    Article  PubMed  CAS  Google Scholar 

  5. Klareskog L, Heijde D van der, Jager JP de et al (2004) TEMPO (Trial of Etanercept and Methotrexate with Radiographic Patient Outcomes) study investigators: 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 363:675–681

    Article  PubMed  CAS  Google Scholar 

  6. Breedveld FC, Weisman MH, Kavanaugh AF et al (2006) 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 54:26–37

    Article  PubMed  CAS  Google Scholar 

  7. Van de Putte LB, Atkins C, Malaise M et al (2004) Efficacy and safety of adalimumab as monotherapy in patients with rheumatoid arthritis for whom previous disease modifying antirheumatic drug treatment has failed. Ann Rheum Dis 63:508–516

    Article  Google Scholar 

  8. Keystone EC, Kavanaugh AF, Sharp JT et al (2004) Radiographic, clinical, and functional outcomes of treatment with adalimumab (a human anti-tumor necrosis factor monoclonal antibody) in patients with active rheumatoid arthritis receiving concomitant methotrexate therapy: a randomized, placebo controlled, 52-week trial. Arthritis Rheum 50:1400–1411

    Article  PubMed  CAS  Google Scholar 

  9. Weinblatt ME, Keystone EC, Furst DE et al (2003) Adalimumab, a fully human anti-tumor necrosis factor alpha monoclonal antibody, for the treatment of rheumatoid arthritis in patients taking concomitant methotrexate: the ARMADA trial. Arthritis Rheum 48:35–45

    Article  PubMed  CAS  Google Scholar 

  10. Maini R, St Clair EW, Breedveld F et al (1999) Infliximab (chimeric antitumour necrosis factor alpha monoclonal antibody) versus placebo in rheumatoid arthritis patients receiving concomitant methotrexate: a randomized phase III trial. ATTRACT Study Group. Lancet 354:1932–1939

    Article  PubMed  CAS  Google Scholar 

  11. Van der Heijde DM, Hof MA van’t, Riel PL van et al (1992) Validity of single variables and composite indices for measuring disease activity in rheumatoid arthritis. Ann Rheum Dis 51:177–181

    Article  Google Scholar 

  12. Felson DT, Anderson JJ, Boers M et al (1995) American College of Rheumatology. Preliminary definition of improvement in rheumatoid arthritis. Arthritis Rheum 38:727–735

    Article  PubMed  CAS  Google Scholar 

  13. Aletaha D, Smolen J, Ward MM (2006) Measuring function in rheumatoid arthritis: identifying reversible and irreversible components. Arthritis Rheum 54:2784–2792

    Article  PubMed  Google Scholar 

  14. Aletaha D, Neogi T, Silman A et al (2010) 2010 Rheumatoid arthritis classification criteria an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum 62(9):2569–2581

    Article  PubMed  Google Scholar 

  15. Heijde D van der, Dankert T, Nieman F et al (1999) Reliability and sensitivity to change of a simplification of the Sharp/van der Heijde radiological assessment in rheumatoid arthritis. Rheum (Oxford) 38:941–947

    Google Scholar 

  16. Pincus T, Yazici Y, Sokka T et al (2003) Methotrexate as the “anchor drug” for the treatment of early rheumatoid arthritis. Clin Exp Rheumatol 21(31):S178–S185

    Google Scholar 

  17. Salliot C, Heijde D van der (2009) Long-term safety of methotrexate monotherapy in patients with rheumatoid arthritis: a systematic literature research. Ann Rheum Dis 68:1100–1104

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  18. Lipsky PE (1994) Harrison’s principles of internal medicine. In: Isselbacher KJ, Braunwald E, Fauci AS et al (eds) Rheumatoid arthritis, 17th edn. McGraw-Hill, New York, pp 1648–1655

  19. Gremese E, Salaffi F, Bosello SL et al (2013) Very early rheumatoid arthritis as a predictor of remission: a multicentre real life prospective study (VERA). Ann Rheum Dis 72(6):858–862. doi:10.1136/annrheumdis-2012-201456

    Article  PubMed  PubMed Central  Google Scholar 

  20. Weinblatt ME, Keystone EC, Cohen MD et al (2011) Factors associated with radiographic progression in patients with rheumatoid arthritis who were treated with methotrexate. J Rheumatol 38(2):242–246

    Article  PubMed  CAS  Google Scholar 

  21. St Clair EW, Heijde DM van der, Smolen JS et al (2004) Combination of infliximab and methotrexate therapy for early rheumatoid arthritis: a randomized, controlled trial. Arthritis Rheum 50:3432–3443

    Article  Google Scholar 

  22. Donahue KE, Gartlehner G, Jonas DE et al (2008) Systematic review: comparative effectiveness and harms of disease-modifying medications for rheumatoid arthritis. Ann Intern Med 148:124–134

    Article  PubMed  Google Scholar 

  23. Rau R, Herborn G, Menninger H, Sangha O (2002) Radiographic outcome after three years of patients with early erosive rheumatoid arthritis treated with intramuscular methotrexate or parenteral gold. Extension of a one-year double blind study in 174 patients. Rheum (Oxford) 41:196–204

    Google Scholar 

  24. Weinblatt ME, Reda D, Henderson W et al (1999) Sulfasalazine treatment for rheumatoid arthritis: a metaanalysis of 15 randomized trials. J Rheumatol 26:2123–2130

    PubMed  CAS  Google Scholar 

  25. Nam JL, Winthrop K, Vollenhoven R van et al (2010) Current evidence for the management of rheumatoid arthritis with biological disease modifying antirheumatic drugs: a systematic literature review informing the EULAR recommendations for the management of RA. Ann Rheum Dis 69:976–986

    Article  PubMed  CAS  Google Scholar 

  26. Gorter SL, Bijlsma H, Cutolo M et al (2010) Current evidence for the management of rheumatoid arthritis with glucocorticoids: a systematic literature review informing the EULAR recommendations for the management of rheumatoid arthritis. Ann Rheum Dis 69:1010–1014. 65

    Article  PubMed  CAS  Google Scholar 

  27. Hamilton J, McInnes IB, Suarez-Almazor ME et al (2000) Antimalarials for treating rheumatoid arthritis. Cochrane Database Syst Rev 4

  28. O’Dell JR, Haire CE, Erikson N et al (1996) Treatment of rheumatoid arthritis with methotrexate alone, sulfasalazine and hydroxychloroquine, or a combination of all three medications. N Engl J Med 334:1287–1291

    Article  Google Scholar 

  29. Calgüneri M, Pay S, Caliskaner Z et al (1999) Combination therapy versus monotherapy for the treatment of patients with rheumatoid arthritis. Clin Exp Rheumatol 17:699–704

    PubMed  Google Scholar 

  30. Van der Heijde DM, Riel PL van, Nuver-Zwart IH, Putte LB van de (1990) Sulphasalazine versus hydroxychloroquine in rheumatoid arthritis: 3-year followup. Lancet 335:539

    Google Scholar 

  31. Sokka T, Kautiainen H, Möttönen T, Hannonen P (1999) Work disability in rheumatoid arthritis 10 years after the diagnosis. J Rheumatol 26(8):1681–1685

    PubMed  CAS  Google Scholar 

  32. Sokka T, Häkkinen A, Kautiainen H et al (2008) Physical inactivity in patients with rheumatoid arthritis: data from twenty-one countries in a cross-sectional, international study. Arthritis Rheum 59(1):42–50

    Article  PubMed  Google Scholar 

  33. Black N (1996) Why we need observational studies to evaluate the effectiveness of health care. BMJ 312:1215–1218

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  34. Rothwell PM (2005) External validity of randomised controlled trials: “to whom do the results of this trial apply?” Lancet 365:82–93

    Google Scholar 

  35. Ware JE, Sherbourne CD (1992) The MOS 36-item short-form health survey (SF-36). Conceptual framework and item selection. Med Care 30:473–483

    Article  PubMed  Google Scholar 

  36. Klareskog L, Heijde D van der, Jager JP de et al (2004) 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 363:675–681

    Article  PubMed  CAS  Google Scholar 

  37. Maini RN, Breedveld FC, Kalden JR et al (1998) Therapeutic efficacy of multiple intravenous infusions of anti-tumor necrosis factor alpha monoclonal antibody combined with low-dose weekly methotrexate in rheumatoid arthritis. Arthritis Rheum 41:1552–1563

    Article  PubMed  CAS  Google Scholar 

  38. Edwards JC, Szczepanski L, Szechinski J et al (2004) Efficacy of B-cell-targeted therapy with rituximab in patients with rheumatoid arthritis. N Engl J Med 350:2572–2581

    Article  PubMed  CAS  Google Scholar 

  39. Grijalva CJ, Chen L, Delzell E et al (2011) Initiation of tumor necrosis factor-α antagonists and the risk of hospitalization for infection in patients with autoimmune diseases. JAMA 306(21):2331–2339

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  40. Strangfeld A, Eveslage M, Schneider M et al (2011) Treatment benefit or survival of the fittest: what drives the time-dependent decrease in serious infection rates under TNF inhibition and what does this imply for the individual patient? Ann Rheum Dis 70(11):1914–1920

    Article  PubMed  CAS  PubMed Central  Google Scholar 

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Acknowledgment

The authors would like to acknowledge the great effort and contribution of Professor Dr. Yusuf Yazici (Associate Professor of Rheumatology, NYU) in reviewing the scientific and statistical contents of this research.

Compliance with ethical guidelines

Conflict of interest. R.H.A. Mohammed, H.H. Kewan, and M. Bukhari state that there are no conflicts of interest.

All studies on humans described in the present manuscript were carried out with the approval of the responsible ethics committee and in accordance with national law and the Helsinki Declaration of 1975 (in its current, revised form). Informed consent was obtained from all patients included in studies.

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Correspondence to R.H.A. Mohammed MD, PhD.

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Mohammed, R., Kewan, H. & Bukhari, M. Assessment of the treat-to-target strategy in patients with refractory rheumatoid arthritis. Z. Rheumatol. 73, 746–753 (2014). https://doi.org/10.1007/s00393-013-1335-2

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