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20-08-2018 | Rheumatoid arthritis | Review | Article

Efficacy of Monotherapy with Biologics and JAK Inhibitors for the Treatment of Rheumatoid Arthritis: A Systematic Review

Journal: Advances in Therapy

Authors: Paul Emery, Janet E. Pope, Klaus Kruger, Ralph Lippe, Ryan DeMasi, Sadiq Lula, Blerina Kola

Publisher: Springer Healthcare

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Abstract

Despite recommendations suggesting that biological and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) should be used in combination with methotrexate in the treatment of rheumatoid arthritis (RA), up to one-third of patients with RA are treated with monotherapy. The objective of the systematic literature review reported here was to evaluate the clinical evidence regarding the efficacy of b/tsDMARDs as monotherapy in the treatment of RA. MEDLINE®, Embase®, and the Cochrane Central Trials Register (to April 11, 2017) and the American College of Rheumatology and European League Against Rheumatism conference proceedings (2010–2016) were searched for randomized controlled trials evaluating the efficacy of b/tsDMARDs as monotherapy for RA in adults. Forty-four monotherapy studies of abatacept, adalimumab, baricitinib, certolizumab pegol, etanercept, sarilumab, sirukumab, tocilizumab, and tofacitinib reported in 71 publications were identified. Tocilizumab had the most studies (14), followed by etanercept (10) and adalimumab (9). These b/tsDMARDs were consistently shown to be efficacious treatments, regardless of whether patients were intolerant of or had never used conventional synthetic (cs) DMARDs. However, better treatment outcomes were usually achieved with combination therapy, and this was observed for all b/tsDMARDs assessed by this review. Only a few studies provided a head-to-head comparison between b/tsDMARD treatments or between b/tsDMARD monotherapy and combination therapy, and as many were initial RA treatments they were not generalizable to usual care. In conclusion, evidence from randomized trials suggests that the b/tsDMARDs studied are effective as monotherapy. In general, some patient responses seem better with combination therapy and the durability of monotherapy is less than combination therapy. There is, however, a need for longer-term head-to-head trials to establish positioning of these interventions in the treatment algorithm for RA.
Funding: Pfizer.
Plain Language Summary: Plain language summary available on the journal website.
Literature
1.
Smolen JS, van der Heijde D, Machold KP, Aletaha D, Landewe R. Proposal for a new nomenclature of disease-modifying antirheumatic drugs. Ann Rheum Dis. 2014;73:3–5.CrossRefPubMed
2.
3.
US Food and Drug Administration. Drugs@FDA: FDA approved drug products. 2017. https://​www.​accessdata.​fda.​gov/​scripts/​cder/​daf/​index.​cfm. Accessed 13 Feb 2018.
4.
Clarke T. FDA declines to approve J&J arthritis drug sirukumab. Reuters. September 22, 2017.
5.
Smolen JS, Landewe R, Bijlsma J, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update. Ann Rheum Dis. 2017;76:960–77.CrossRefPubMed
6.
Jørgensen TS, Kristensen LE, Christensen R, et al. Effectiveness and drug adherence of biologic monotherapy in routine care of patients with rheumatoid arthritis: a cohort study of patients registered in the Danish biologics registry. Rheumatology (Oxford). 2015;54:2156–65.
7.
Choy E, Taylor P, McAuliffe S, Roberts K, Sargeant I. Variation in the use of biologics in the management of rheumatoid arthritis across the UK. Curr Med Res Opin. 2012;28:1733–41.CrossRefPubMed
8.
Aaltonen KJ, Turunen JH, Sokka T, Puolakka K, Valleala H. A survey on the medication adherence to methotrexate among rheumatoid arthritis patients treated with self-administered biologic drugs. Clin Exp Rheumatol. 2016;34:694–7.PubMed
9.
Yazici Y, Shi N, John A. Utilization of biologic agents in rheumatoid arthritis in the United States: analysis of prescribing patterns in 16,752 newly diagnosed patients and patients new to biologic therapy. Bull NYU Hosp Jt Dis. 2008;66:77–85.PubMed
10.
Emery P, Sebba A, Huizinga TW. Biologic and oral disease-modifying antirheumatic drug monotherapy in rheumatoid arthritis. Ann Rheum Dis. 2013;72:1897–904.CrossRefPubMed
11.
Engel-Nitz NM, Ogale S, Kulakodlu M. Use of anti-tumor necrosis factor therapy: a retrospective study of monotherapy and adherence to combination therapy with non-biologic disease-modifying anti-rheumatic drugs. Rheumatol Ther. 2015;2:127–39.CrossRefPubMedPubMedCentral
12.
Soliman MM, Ashcroft DM, Watson KD, 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.CrossRefPubMed
13.
Buckley F, Finckh A, Huizinga TW, Dejonckheere F, Jansen JP. Comparative efficacy of novel DMARDs as monotherapy and in combination with methotrexate in rheumatoid arthritis patients with inadequate response to conventional DMARDs: a network meta-analysis. J Manag Care Spec Pharm. 2015;21:409–23.PubMed
14.
Jansen JP, Buckley F, Dejonckheere F, Ogale S. Comparative efficacy of biologics as monotherapy and in combination with methotrexate on patient reported outcomes (PROs) in rheumatoid arthritis patients with an inadequate response to conventional DMARDs—a systematic review and network meta-analysis. Health Qual Life Outcomes. 2014;12:102.CrossRefPubMedPubMedCentral
15.
Tarp S, Furst DE, Dossing A, et al. Defining the optimal biological monotherapy in rheumatoid arthritis: a systematic review and meta-analysis of randomised trials. Semin Arthritis Rheum. 2017;46:699–708.CrossRefPubMed
16.
Jadad AR, Moore RA, Carroll D, et al. Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials. 1996;17:1–12.CrossRefPubMed
17.
Downs SH, Black N. The feasibility of creating a checklist for the assessment of the methodological quality both of randomised and non-randomised studies of health care interventions. J Epidemiol Community Health. 1998;52:377–84.CrossRefPubMedPubMedCentral
18.
Emery P, Burmester GR, Bykerk VP, et al. Evaluating drug-free remission with abatacept in early rheumatoid arthritis: results from the phase 3b, multicentre, randomised, active-controlled AVERT study of 24 months, with a 12-month, double-blind treatment period. Ann Rheum Dis. 2015;74:19–26.CrossRefPubMed
19.
Emery P, Burmester GR, Bykerk VP, et al. Induction of clinical remission followed by drug free withdrawal with abatacept combination and monotherapy in early RA: results from the AVERT study over 18 months [abstract]. Ann Rheum Dis. 2014;73:69.CrossRef
20.
Burmester G, Furst DE, Combe BG, et al. Stringent criteria for low disease activity and remission after 12 months of treatment, and after treatment withdrawal, with abatacept monotherapy, abatacept with methotrexate or methotrexate alone in early rheumatoid arthritis. Arthritis Rheumatol. 2014;66:S1076-S.
21.
Yazici Y, Gandhi KK, Alemao E, Furst DE. Routine assessment of patient index data 3 (RAPID3)—defined remission is as stringent as ACR/EULAR Boolean-defined remission in a clinical trial of patients with early rheumatoid arthritis treated with abatacept [abstract]. Arthritis Rheumatol. 2015;67:1644.
22.
Furst DE, Bykerk VP, Burmester GR, et al. Treatment effects and minimal clinically important differences in patient-reported outcomes following treatment and withdrawal of abatacept, methotrexate or combination therapy in patients with early rheumatoid arthritis [abstract]. Ann Rheum Dis. 2015;74:1044.CrossRef
23.
Moreland LW, Alten R, Van den Bosch F, et al. Costimulatory blockade in patients with rheumatoid arthritis: a pilot, dose-finding, double-blind, placebo-controlled clinical trial evaluating CTLA-4Ig and LEA29Y eighty-five days after the first infusion. Arthritis Rheum. 2002;46:1470–9.CrossRefPubMed
24.
Breedveld FC, Weisman MH, Kavanaugh AF, 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.CrossRefPubMed
25.
Miyasaka N, Investigators CS. Clinical investigation in highly disease-affected rheumatoid arthritis patients in Japan with adalimumab applying standard and general evaluation: the CHANGE study. Mod Rheumatol. 2008;18:252–62.CrossRefPubMedPubMedCentral
26.
van de Putte LB, Atkins C, Malaise M, et al. 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. 2004;63:508–16.CrossRefPubMedPubMedCentral
27.
Fleischmann R, Cutolo M, Genovese MC, et al. Phase IIb dose-ranging study of the oral JAK inhibitor tofacitinib (CP-690,550) or adalimumab monotherapy versus placebo in patients with active rheumatoid arthritis with an inadequate response to disease-modifying antirheumatic drugs. Arthritis Rheum. 2012;64:617–29.CrossRefPubMed
28.
Popa C, Netea MG, Radstake T, et al. Influence of anti-tumour necrosis factor therapy on cardiovascular risk factors in patients with active rheumatoid arthritis. Ann Rheum Dis. 2005;64:303–5.CrossRefPubMed
29.
Gabay C, Emery P, van Vollenhoven R, 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.CrossRefPubMed
30.
Strand V, Lampl K, Birchwood C, et al. Patient-reported outcomes in two randomized, controlled trials (RCTs) in patients with rheumatoid arthritis (RA) treated with tocilizumab (TCZ) monotherapy compared with methotrexate (MTX) or adalimumab (ADA). Arthritis Rheumatol. 2016;68:2515.
31.
Burmester G, Lin Y, Patel R, et al. Efficacy and safety of sarilumab versus adalimumab in a phase 3, randomized, double-blind, monotherapy study in patients with active rheumatoid arthritis with intolerance or inadequate response to methotrexate. Arthritis Rheumatol. 2016;68:3221.
32.
Burmester GR, Lin Y, Patel R, et al. Efficacy and safety of sarilumab monotherapy versus adalimumab monotherapy for the treatment of patients with active rheumatoid arthritis (MONARCH): a randomised, double-blind, parallel-group phase III trial. Ann Rheum Dis. 2017;76:840–7.CrossRefPubMed
33.
Taylor PC, Schiff M, Wang Q, et al. Efficacy and safety of monotherapy with sirukumab, an anti-IL-6 cytokine monoclonal antibody, compared with adalimumab monotherapy in biologic-naive patients with active rheumatoid arthritis: results of a global, randomized, double-blind, parallel-group, phase 3 study [abstract]. Arthritis Rheumatol. 2016;68:3222.CrossRef
34.
Fleischmann R, Takeuchi T, Schlichting DE, et al. Baricitinib, methotrexate, or baricitinib plus methotrexate in patients with early rheumatoid arthritis who had received limited or no treatment with disease-modifying anti-rheumatic drugs (DMARDs): phase 3 trial results. Arthritis Rheumatol. 2015;67:1045.CrossRef
35.
Fleischmann R, Schiff M, van der Heijde D, et al. Baricitinib, methotrexate, or combination in patients with rheumatoid arthritis and no or limited prior disease-modifying antirheumatic drug treatment. Arthritis Rheumatol. 2017;69:506–17.CrossRefPubMedPubMedCentral
36.
Weinblatt ME, Fleischmann R, Huizinga TW, et al. Efficacy and safety of certolizumab pegol in a broad population of patients with active rheumatoid arthritis: results from the REALISTIC phase IIIb study. Rheumatology (Oxford). 2012;51:2204–14.CrossRef
37.
Yamamoto K, Takeuchi T, Yamanaka H, et al. Efficacy and safety of certolizumab pegol without methotrexate co-administration in Japanese patients with active rheumatoid arthritis: the HIKARI randomized, placebo-controlled trial. Mod Rheumatol. 2014;24:552–60.CrossRefPubMed
38.
Fleischmann R, Vencovsky J, van Vollenhoven RF, et al. Efficacy and safety of certolizumab pegol monotherapy every 4 weeks in patients with rheumatoid arthritis failing previous disease-modifying antirheumatic therapy: the FAST4WARD study. Ann Rheum Dis. 2009;68:805–11.CrossRefPubMed
39.
Johnsen AK, Schiff MH, Mease PJ, et al. Comparison of 2 doses of etanercept (50 vs 100 mg) in active rheumatoid arthritis: a randomized double blind study. J Rheumatol. 2006;33:659–64.PubMed
40.
Combe B, Codreanu C, Fiocco U, et al. Etanercept and sulfasalazine, alone and combined, in patients with active rheumatoid arthritis despite receiving sulfasalazine: a double-blind comparison. Ann Rheum Dis. 2006;65:1357–62.CrossRefPubMedPubMedCentral
41.
Combe B, Codreanu C, Fiocco U, et al. Efficacy, safety and patient-reported outcomes of combination etanercept and sulfasalazine versus etanercept alone in patients with rheumatoid arthritis: a double-blind randomised 2-year study. Ann Rheum Dis. 2009;68:1146–52.CrossRefPubMed
42.
Kameda H, Kanbe K, Sato E, et al. Etanercept (ETN) plus methotrexate (MTX) combination therapy resulted in a better radiographic outcome than ETN monotherapy even in patients with active rheumatoid arthritis despite MTX treatment: 104-week results from the JESMR study [abstract]. Arthritis Rheum. 2010;62:1812.CrossRef
43.
Kameda H, Ueki Y, Saito K, et al. Etanercept (ETN) with methotrexate (MTX) is better than ETN monotherapy in patients with active rheumatoid arthritis despite MTX therapy: a randomized trial. Mod Rheumatol. 2010;20:531–8.CrossRefPubMed
44.
Klareskog L, van der Heijde D, de Jager JP, 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.CrossRefPubMed
45.
van der Heijde D, Klareskog L, Rodriguez-Valverde V, et al. Comparison of etanercept and methotrexate, alone and combined, in the treatment of rheumatoid arthritis: two-year clinical and radiographic results from the TEMPO study, a double-blind, randomized trial. Arthritis Rheum. 2006;54:1063–74.CrossRefPubMed
46.
van der Heijde D, Klareskog L, Landewe R, et al. Disease remission and sustained halting of radiographic progression with combination etanercept and methotrexate in patients with rheumatoid arthritis. Arthritis Rheum. 2007;56:3928–39.CrossRefPubMed
47.
Moreland LW, Schiff MH, Baumgartner SW, et al. Etanercept therapy in rheumatoid arthritis. A randomized, controlled trial. Ann Intern Med. 1999;130:478–86.CrossRefPubMed
48.
Mathias SD, Colwell HH, Miller DP, Moreland LW, Buatti M, Wanke L. Health-related quality of life and functional status of patients with rheumatoid arthritis randomly assigned to receive etanercept or placebo. Clin Ther. 2000;22:128–39.CrossRefPubMed
49.
Bathon JM, Martin RW, Fleischmann RM, et al. A comparison of etanercept and methotrexate in patients with early rheumatoid arthritis. N Engl J Med. 2000;343:1586–93.CrossRefPubMed
50.
Hu D, Bao C, Chen S, et al. A comparison study of a recombinant tumor necrosis factor receptor: Fc fusion protein (rhTNFR:Fc) and methotrexate in treatment of patients with active rheumatoid arthritis in China. Rheumatol Int. 2009;29:297–303.CrossRefPubMed
51.
Takeuchi T, Miyasaka N, Zang C, et al. A phase 3 randomized, double-blind, multicenter comparative study evaluating the effect of etanercept versus methotrexate on radiographic outcomes, disease activity, and safety in Japanese subjects with active rheumatoid arthritis. Mod Rheumatol. 2013;23:623–33.CrossRefPubMed
52.
Genovese MC, Cohen S, Moreland L, et al. Combination therapy with etanercept and anakinra in the treatment of patients with rheumatoid arthritis who have been treated unsuccessfully with methotrexate. Arthritis Rheum. 2004;50:1412–9.CrossRefPubMed
53.
Weinblatt M, Schiff M, Goldman A, et al. Selective costimulation modulation using abatacept in patients with active rheumatoid arthritis while receiving etanercept: a randomised clinical trial. Ann Rheum Dis. 2007;66:228–34.CrossRefPubMed
54.
Takeuchi T, Yamanaka H, Harigai M, et al. One-year safety of sirukumab monotherapy: results from a randomized, double-blind, parallel-group, multicenter study in Japanese subjects with moderate to severe rheumatoid arthritis [abstract]. Arthritis Rheumatol. 2015;67:1672.
55.
Takeuchi T, Thorne C, Karpouzas G, et al. Efficacy and safety of sirukumab in patients with active rheumatoid arthritis despite disease-modifying anti-rheumatic drug treatment: results of a randomized, double-blind, placebo-controlled study [abstract]. Ann Rheum Dis. 2016;75:717.
56.
Aletaha D, Bingham CO 3rd, Tanaka Y, et al. Efficacy and safety of sirukumab in patients with active rheumatoid arthritis refractory to anti-TNF therapy (SIRROUND-T): a randomised, double-blind, placebo-controlled, parallel-group, multinational, phase 3 study. Lancet. 2017;389:1206–17.CrossRefPubMed
57.
Burmester GR, Rigby W, van Vollenhoven R, et al. Tocilizumab in combination therapy and monotherapy versus methotrexate in methotrexate-naive patients with early rheumatoid arthritis: clinical and radiographic outcomes from a randomized, placebo-controlled trial [abstract]. Arthritis Rheum. 2013;65:2767.
58.
Burmester GR, Rigby W, Ronald F, et al. Tocilizumab combination therapy or monotherapy or methotrexate monotherapy in methotrexate-naive patients with early rheumatoid arthritis: 2-year clinical and radiographic results from a randomized, placebo-controlled trial [abstract]. Arthritis Rheumatol. 2014;66:S811.
59.
Burmester GR, Rigby WF, van Vollenhoven RF, et al. Tocilizumab in early progressive rheumatoid arthritis: FUNCTION, a randomised controlled trial. Ann Rheum Dis. 2016;75:1081–91.CrossRefPubMed
60.
Burmester G, Pethö-Schramm A, Keane C, Jones G. Tocilizumab monotherapy in early rheumatoid arthritis: data from two phase 3 randomized controlled trials [abstract]. Arthritis Rheumatol. 2015;67:1650.
61.
Weinblatt ME, Kremer J, Cush J, et al. Tocilizumab as monotherapy or in combination with nonbiologic disease-modifying antirheumatic drugs: twenty-four-week results of an open-label, clinical practice study. Arthritis Care Res (Hoboken). 2013;65:362–71.CrossRef
62.
Takeuchi T, Kaneko Y, Atsumi T, et al. Adding tocilizumab or switching to tocilizumab monotherapy in RA patients with inadequate response to methotrexate: 24-week results from a randomized controlled study (SURPRISE study) [abstract]. Ann Rheum Dis. 2013;72:62.CrossRef
63.
Dougados M, Kissel K, Sheeran T, 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.CrossRefPubMed
64.
Herold M, Fasching P, Graninger W, Lunzer R, Zamani O, Leeb B. Efficacy of tocilizumab monotherapy in patients with RA is not influenced by ACPA positivity. Arthritis Rheumatol. 2015;67:499.
65.
Pablos JL, Navarro Sarabia F, Blanco FJ, et al. Switch from tocilizumab + methotrexate to tocilizumab monotherapy. Maintenance of response in patients with rheumatoid arthritis at low disease activity [abstract]. Arthritis Rheumatol. 2015;67:S10.
66.
Nishimoto N, Yoshizaki K, Miyasaka N, et al. Treatment of rheumatoid arthritis with humanized anti-interleukin-6 receptor antibody: a multicenter, double-blind, placebo-controlled trial. Arthritis Rheum. 2004;50:1761–9.CrossRefPubMed
67.
Ogata A, Tanimura K, Sugimoto 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.CrossRef
68.
Ogata A, Amano K, Dobashi H, et al. Longterm safety and efficacy of subcutaneous tocilizumab monotherapy: results from the 2-year open-label extension of the MUSASHI study. J Rheumatol. 2015;42:799–809.CrossRefPubMed
69.
Ogata A, Takagi N, Miwa H. A randomized, double-blind, parallel-group, phase III study of shortening the dosing interval of subcutaneous tocilizumab monotherapy in RA patients with an inadequate response to subcutaneous tocilizumab every other week [abstract]. Arthritis Rheumatol. 2016;68:1592.
70.
Durez P, Depresseux G, Toukap AN, et al. Rate of remission by tocilizumab or methotrexate induction therapy in early active rheumatoid arthritis: results of the Tomera trial. Ann Rheum Dis. 2013;72:623.
71.
Jones G. The AMBITION trial: tocilizumab monotherapy for rheumatoid arthritis. Expert Rev Clin Immunol. 2010;6:189–95.CrossRefPubMed
72.
Nishimoto N, Hashimoto J, Miyasaka N, et al. Study of active controlled monotherapy used for rheumatoid arthritis, an IL-6 inhibitor (SAMURAI): evidence of clinical and radiographic benefit from an x ray reader-blinded randomised controlled trial of tocilizumab. Ann Rheum Dis. 2007;66:1162–7.CrossRefPubMedPubMedCentral
73.
Kawashiri SY, Kawakami A, Yamasaki S, et al. Effects of the anti-interleukin-6 receptor antibody, tocilizumab, on serum lipid levels in patients with rheumatoid arthritis. Rheumatol Int. 2011;31:451–6.CrossRefPubMed
74.
Nishimoto N, Miyasaka N, Yamamoto K, et al. Study of active controlled tocilizumab monotherapy for rheumatoid arthritis patients with an inadequate response to methotrexate (SATORI): significant reduction in disease activity and serum vascular endothelial growth factor by IL-6 receptor inhibition therapy. Mod Rheumatol. 2009;19:12–9.CrossRefPubMed
75.
Fleischmann R, Kremer J, Cush J, et al. Placebo-controlled trial of tofacitinib monotherapy in rheumatoid arthritis. N Engl J Med. 2012;367:495–507.CrossRefPubMed
76.
Strand V, Kremer J, Wallenstein G, et al. Effects of tofacitinib monotherapy on patient-reported outcomes in a randomized phase 3 study of patients with active rheumatoid arthritis and inadequate responses to DMARDs. Arthritis Res Ther. 2015;17:307.CrossRefPubMedPubMedCentral
77.
Tanaka Y, Takeuchi T, Yamanaka H, et al. Tofacitinib (CP-690,550), an oral Janus kinase inhibitor, as monotherapy in Japanese patients with active rheumatoid arthritis: a 12-week phase 2b study [abstract]. Arthritis Rheum. 2011;63:2192.CrossRef
78.
Tanaka Y, Takeuchi T, Yamanaka H, Nakamura H, Toyoizumi S, Zwillich S. Efficacy and safety of tofacitinib as monotherapy in Japanese patients with active rheumatoid arthritis: a 12-week, randomized, phase 2 study. Mod Rheumatol. 2015;25:514–21.CrossRefPubMedPubMedCentral
79.
Kremer JM, Bloom BJ, Breedveld FC, et al. The safety and efficacy of a JAK inhibitor in patients with active rheumatoid arthritis: results of a double-blind, placebo-controlled phase IIa trial of three dosage levels of CP-690,550 versus placebo. Arthritis Rheum. 2009;60:1895–905.CrossRefPubMed
80.
Fleischmann R, Strand V, Wilkinson B, Kwok K, Bananis E. Relationship between different clinical measurements and patient-reported outcomes: results from a phase 3 study of tofacitinib or methotrexate in methotrexate-naïve patients with rheumatoid arthritis [abstract]. Arthritis Rheumatol. 2014;66:S1086.
81.
Fleischmann R, Strand V, Wilkinson B, Kwok K, Bananis E. Relationship between different clinical measurements and patient-reported outcomes: results from a phase 3 study of tofacitinib or methotrexate in methotrexate-naïve patients with rheumatoid arthritis [abstract]. Ann Rheum Dis. 2015;74:259.
82.
Lee EB, Fleischmann RM, Hall S, et al. Radiographic, clinical and functional comparison of tofacitinib monotherapy versus methotrexate in methotrexate-naive patients with rheumatoid arthritis [abstract]. Arthritis Rheum. 2012;64:S1049.
83.
Fleischmann R, Huizinga TWJ, Kavanaugh A, et al. An analysis of the efficacy of tofacitinib monotherapy in MTX-naïve patients with early RA compared with patients with established RA [abstract]. Arthritis Rheumatol. 2015;67:2741.CrossRef
84.
Fleischmann RM, Huizinga TW, Kavanaugh AF, et al. Efficacy of tofacitinib monotherapy in methotrexate-naive patients with early or established rheumatoid arthritis. RMD Open. 2016;2:e000262.CrossRefPubMedPubMedCentral
85.
Alten R, Strand V, Fleischmann R, et al. Effects of tofacitinib monotherapy versus methotrexate on patient-reported outcomes in the 2-year phase 3 oral start trial in methotrexate-naive patients with rheumatoid arthritis [abstract]. Ann Rheum Dis. 2014;73:118–9.
86.
Strand V, Lee EB, Fleischmann R, et al. Tofacitinib versus methotrexate in rheumatoid arthritis: patient-reported outcomes from the randomised phase III ORAL Start trial. RMD Open. 2016;2:e000308.CrossRefPubMedPubMedCentral
87.
Strand V, Bergman MJ, Lee EB, et al. Long-term clinical, radiographic and patient-reported outcomes based on RAPID3 responses with tofacitinib at 6 months [abstract]. Arthritis Rheumatol. 2016;68:1648.CrossRef
88.
Charles-Schoeman C, van der Heijde D, Burmester G, et al. Effect of glucocorticoids on clinical and radiographic efficacy outcomes in methotrexate-naive patients with RA receiving tofacitinib or methotrexate monotherapy: analysis of data from a phase 3 trial. Arthritis Rheumatol. 2016;68:2606.CrossRef
89.
Patane M, Ciriaco M, Chimirri S, et al. Interactions among low dose of methotrexate and drugs used in the treatment of rheumatoid arthritis. Adv Pharmacol Sci. 2013;2013:313858.PubMedPubMedCentral
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