Introduction
General principles of drug therapy for RA
Early treatment
Tight control
Methotrexate as an “anchor drug”
Biological agents
The use of glucocorticoids
Improved outcomes of RA
Treatments for RA in selected clinical cohorts and cross-sectional studies
The initial DMARD for early RA
Country | Cohort, [reference] | Enrollment period | Percentage of patients who started selected DMARDs | |||||
---|---|---|---|---|---|---|---|---|
IM gold (%) | AM (%) | SSZ (%) | MTX (%) | Other DMARDs (%) | No DMARDs (%) | |||
1970s | ||||||||
Finland | Heinola Cohort, Jantti et al. [76] | 1973–1975 | 56 | 36 | 0 | 0 | 4 | 4 |
1980s | ||||||||
Finland | Jyvasyla Cohort1983–1985 Sokka et al. [46] | 1983–1985 | 70 | 30 | 0 | 0 | 0 | 0 |
Austria | Aletaha et al. [53] | 1985 | 87 | 7 | 0 | 0 | 6 | |
NL | Welsing et al. [56] | 1985–1990 | Na | Na | 60 | 2 | 38 | |
Early 1990s | ||||||||
Austria | Aletaha et al. [53] | 1992 | 20 | 46 | 22 | 4 | 8 | |
NL | Welsing et al. [56] | 1991–1995 | Na | Na | 82 | 9 | 9 | |
UK | ERAS, Young et al. [77] | Before 1994 | 8 | 2 | 61 | 2 | 11 | 16 |
UK | aNOAR, Bukhari et al. [78] | Early 1990s | 3 | 4 | 37 | 3 | 1 | 52 |
Greece | Papadopoulos et al. [79] | 1987–1995 | 5 | 30 | 0 | 21 | 44 | 0 |
USA | Western Consortium, Paulus et al. [80] | 1993–1996 | 4 | 17 | 7 | 36 | 0 | 36 |
Sweden | BARFOT, Forslind et al. [81] | 1993–1997 | 0 | 0 | 34 | 24 | 8 | 34 |
Late 1990s | ||||||||
Finland | Jyvaskyla Cohort 1995–1996, Sokka et al. [46] | 1995–1996 | 3 | 1 | 95 | 1 | 0 | 0 |
Finland | Jyvaskyla 1997, Makinen et al. [82] | 1997 | Na | Na | 73 | 20 | 6 | 1 |
Sweden | Carli et al. [83] | 1997 | Na | Na | 30 | 23 | 11 | 33 |
Austria | Aletaha et al. [53] | 1998 | 1 | 40 | 29 | 29 | 1 | |
NL | Welsing et al. [56] | 1996–2000 | Na | Na | 76 | 10 | 14 | |
Early 2000s | ||||||||
USA | ERATER, Sokka and Pincus [69] | 1998–2003 | 0 | 7 | 1 | 82 | 3 | 7 |
Sweden | Carli et al. [83] | 2001 | Na | Na | 20 | 54 | 6 | 17 |
USA | SONORA, Bombardier et al. [84] | Early 2000s | 0 | 16 | 5 | 27 | 17 | 35 |
Italy | GIARA, CER [85] | b2001–2002 | Na | 18 | 1.2 | 19 | 11 | 51 |
The use of DMARDs in selected early RA cohorts
Trends in the use of DMARDs
Country | Register or cohort, [reference] | Study period | Percentage of patients taking selected DMARDs | Total | ||||||
---|---|---|---|---|---|---|---|---|---|---|
IM gold (%) | AM (%) | SSZ (%) | MTX (%) | Biol (%) | Other DMARD (%) | No DMARD (%) | ||||
1970s | ||||||||||
UK | Bath, Rasker et al. [86] | 15-yr follow-up | 35 | 55 | 0 | 0 | 0 | 13 | Na | Ever used |
USA | Nashville, TN, Pincus et al. [3] | 1973 | 60 | 26 | 0 | 0 | 0 | Na | Na | Ever used |
1980s | ||||||||||
Norway | Tromsø, Riise et al. [87] | Year of diagnosis 1979–1987 | 40 | 39 | 8 | 7 | 0 | 45 | Na | % of started DMARDs |
USA | Nashville, TN, Pincus et al. [41] | 1985 | 10 | 5 | 0 | 10 | 0 | 9 | 66 | 100% |
UK | GPRD database, Edwards et al. [88] | 1987 | 13 | 0 | 32 | 2 | 0 | 14 | 39 | 100% |
Finland | Jyväskylä Cohort 1983–1985, Sokka et al. [46] | 1988–1990 | 19 | 7 | 9 | 12 | 0 | 30 | 23 | 100% |
NL | Leiden, van Schaardenburg et al. [89] | 1989–1990 | 25 | 63 | 3 | 0 | 0 | 9 | Na | Ever used |
Early 1990s | ||||||||||
Norway | Tromsø, Riise et al. [87] | Year of diagnosis 1988–1996 | 12 | 29 | 24 | 40 | 0 | 48 | Na | % of started DMARDs |
Japan | Tokushima, Hamada et al. [90] | Enrollment 1980–1990 | 41 | 0 | 17 | 22 | 0 | >63 | 0 | aEver used |
Finland | Jyväskylä Cohort 1988–1999, Sokka et al. [46] | 1993–1994 | 24 | 0 | 15 | 18 | 0 | 14 | 29 | 100% |
Late 1990s | ||||||||||
Finland | Heinola, Jäntti et al. [65] | 1995–1996 | 16 | 13 | 19 | 12 | 0 | 40 | 100 | |
UK | London, Gordon et al. [91] | 1996 | 18 | 12 | 15 | 36 | 0 | 8 | 11 | 100% |
Norway | Oslo RA register, Kvien [92] | 1996–1997 | 47 | 35 | 35 | 49 | 0 | Na | 18 | Ever used |
Sweden | Malmö RA register, Söderlin et al. [93] | 1997 | Na | Na | Na | 24 | 0 | 28 | 48 | 100% |
USA | Western Consortium, Paulus et al. [80] | 1995–1998 | 0 | 31 | 12 | 57 | 0 | Na | Na | 100% |
Sweden | BARFOT, Forslind et al. [81] | 1997 | Na | Na | 15 | 33 | 0 | 19 | 33 | 100% |
UK | Bath, Minaur et al. [62] | 40-year follow-up | 46 | 70 | 3 | 4 | 0 | 34 | 20 | Ever used |
Sweden | 1999 | 5 | 26 | 11 | 15 | 0 | 43 | 25 | Ever used | |
Lithuania | Vilnius, Dadoniene et al. [96] | 1999 | 28 | 50 | 49 | 36 | 0 | 35 | 6 | Ever used |
Spain | EMECAR, Gonzalez-Alvaro [97] | 1999–2000 | 6 | 8 | 3 | 32 | 0 | b28 | 23 | 100% |
Early 2000s | ||||||||||
USA | Nashville, TN, Pincus et al. [41] | 2000 | 1 | 4 | 0 | 73 | 4 | 5 | 13 | 100% |
USA | ERATER Sokka and Pincus [69] | 2001 | 0 | 16 | 4 | 89 | 14 | 22 | Na | Ever used |
Finland | Jyvaskyla, Cohort 1995–1996, Sokka et al. [46] | 2000–2001 | 7 | 2 | 10 | 69 | 1 | 0 | 11 | 100% |
Germany | National database, Thiele et al. [98] | c2001 | 2 | 5 | 7 | 56 | 4 | 17 | 9 | 100% |
Norway | Norwegian DMARD register, Kvien et al. [99] | 2001 | Na | Na | 24 | 38 | 10 | 28 | – | 100% |
Sweden | Malmö RA register, Söderlin et al. [93] | 2002 | Na | Na | Na | 44 | 14 | 11 | 31 | 100% |
UK | GPRD database, Edwards et al. [88] | 2002 | 2 | 8 | 26 | 30 | 0 | 2 | 32 | 100% |
Norway | Norwegian DMARD register, Kvien et al. [99] | 2004 | Na | Na | 8 | 69 | 13 | 10 | – | 100% |
Late 2000s | ||||||||||
Japan | IORRA, Yamanaka et al. [100] | 2006 | Na | Na | Na | 59 | 3 | 27 | 11 | 100% |
UAE | Dubai, Badsha et al. [101] | 2006 | Na | Na | Na | 29 | 2 | 11 | 58 | 100% |
Limitations of available data concerning DMARDs
DMARDs in QUEST-RA
Country | Sites | Patients | Female (%) | Age (years) | Disease duration (years) | DMARD delay (months) | Education (years) | RF+ (%) | DAS 28 | HAQ | Taking now (%) | ||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Pred | MTX | Any biological | |||||||||||
Mean | Mean | Median | Median | Median | Median | ||||||||
Netherlands | 3 | 317 | 66.3 | 59.2 | 9.2 | 5.5 | 11.0 | 68.8 | 2.9 | 0.8 | 16.1 | 74.1 | 19.6 |
Greece | 3 | 300 | 75.7 | 57.9 | 11.8 | 7.0 | 12.0 | 52.1 | 3.1 | 0.3 | 70.7 | 71.3 | 47.0 |
Finland | 3 | 304 | 72.4 | 58.5 | 13.5 | 7.0 | 9.0 | 74.8 | 3.1 | 0.6 | 51.0 | 61.5 | 12.5 |
USA | 3 | 301 | 72.9 | 57.5 | 9.3 | 9.0 | 13.0 | 70.9 | 3.2 | 0.6 | 60.1 | 71.8 | 27.6 |
Denmark | 3 | 301 | 76.7 | 57.8 | 12.0 | 10.1 | 10.0 | 73.3 | 3.3 | 0.6 | 14.6 | 71.1 | 21.3 |
Spain | 3 | 302 | 73.5 | 59.8 | 10.6 | 14.0 | 10.0 | 72.5 | 3.4 | 0.9 | 46.7 | 56.3 | 23.2 |
France | 4 | 389 | 77.9 | 55.3 | 12.8 | 8.0 | 10.0 | 75.3 | 3.6 | 0.9 | 60.9 | 57.1 | 44.2 |
Sweden | 3 | 260 | 71.8 | 59.4 | 12.5 | 12.0 | 10.0 | 81.6 | 3.6 | 0.9 | 41.2 | 65.8 | 26.9 |
Ireland | 3 | 240 | 64.3 | 56.4 | 11.3 | 11.0 | 12.0 | 79.6 | 4.0 | 0.8 | 31.3 | 71.7 | 32.1 |
Turkey | 3 | 309 | 85.6 | 51.9 | 11.6 | 12.0 | 5.0 | 67.6 | 4.1 | 0.9 | 57.3 | 69.3 | 5.8 |
UK | 3 | 145 | 77.9 | 59.6 | 15.0 | 12.0 | 12.0 | 81.4 | 4.1 | 0.9 | 28.3 | 69.7 | 14.5 |
Germany | 3 | 225 | 83.6 | 58.8 | 13.4 | 15.0 | 10.0 | 60.9 | 4.3 | 0.8 | 26.7 | 45.8 | 22.7 |
Canada | 1 | 100 | 78.8 | 57.4 | 12.4 | 12.0 | 12.0 | 82.8 | 4.3 | 1.0 | 25.0 | 49.0 | 23.0 |
Italy | 4 | 336 | 78.2 | 61.0 | 10.5 | 9.0 | 8.0 | 71.4 | 4.5 | 1.1 | 51.8 | 53.3 | 12.5 |
Estonia | 3 | 168 | 85.5 | 55.8 | 11.8 | 12.0 | 12.0 | 68.1 | 4.7 | 1.1 | 40.5 | 53.6 | 0.6 |
Latvia | 1 | 61 | 80.3 | 52.4 | 13.4 | 23.0 | 12.5 | 81.7 | 5.1 | 1.4 | 55.7 | 75.4 | 27.9 |
Hungary | 3 | 153 | 87.4 | 57.9 | 12.6 | 12.0 | 12.0 | 92.8 | 5.2 | 1.4 | 38.6 | 62.7 | 12.4 |
Poland | 7 | 642 | 86.7 | 53.2 | 11.5 | 4.0 | 12.0 | 70.3 | 5.3 | 1.4 | 58.9 | 65.0 | 6.1 |
Lithuania | 2 | 300 | 82.9 | 54.1 | 10.7 | 13.0 | 13.0 | 78.4 | 5.6 | 1.4 | 80.7 | 55.7 | 9.3 |
Argentina | 2 | 246 | 90.2 | 51.4 | 9.9 | 13.0 | 9.0 | 90.5 | 5.6 | 1.0 | 63.4 | 48.8 | 2.8 |
Serbia | 1 | 100 | 88.0 | 59.2 | 10.1 | 11.1 | 8.0 | 71.4 | 6.1 | 1.6 | 54.0 | 54.0 | 0.0 |
Total | 61 | 5,499 | 78.6 | 56.7 | 11.5 | 10.0 | 11.0 | 73.2 | 4.1 | 1.0 | 48.6 | 62.5 | 19.0 |
DMARD | (%) |
---|---|
Prednisone | 72 |
Intramuscular gold | 23 |
Antimalarials | 42 |
Sulfasalazine | 46 |
Methotrexate | 86 |
Any biological agent | 24 |
Leflunomide | 22 |
Cyclosporin A | 9.6 |
Azathioprine | 7.5 |
D-penicillamine | 6.9 |