Treatment Comparison in Rheumatoid Arthritis: Head-to-Head Trials and Innovative Study Designs

Table 2

Summary of head-to-head trials in rheumatoid arthritis.

Reference	Study design	Drugs	Follow-up	Number of patients	Primary endpoint	Results
sDMARDs versus sDMARDs
Weinblatt et al., 1990 [106]	Randomized double-blind controlled	AUR versus MTX	36 wks	138 versus 142	TJC, SJC, PhGA, PtGA	MTX is more effective and better tolerated than AUR
Williams et al., 1992 [107]	Randomized double-blind controlled	AUR versus MTX versus AUR + MTX	48 wks	115 versus 114 versus 106	TJC, SJC, PhGA, PtGA	No differences
Jeurissen et al., 1991 [108, 109]	Randomized double-blind controlled	AZA versus MTX	48 wks	33 versus 31	Ritchie index, TJC, SJC, VAS pain, PtGA	MTX is more efficacious and more rapid than AZA
Willkens et al., 1995 [110]	Randomized double-blind controlled	AZA versus MTX versus AZA + MTX	48 wks	73 versus 67 versus 69	TJC, SJC, PhGA, PtGA, HAQ, mTSS	MTX is more efficacious than AZA. Trend toward decrease radiographic progression only in MTX
Drosos et al., 1998 [111]	Randomized open labeled trial	CSA versus MTX	104 wks	52 versus 51	TJC, SJC, VAS pain, Larsen score	No differences in efficacy and radiographic progression
Ferraccioli et al., 2002 [112]	Open randomized controlled	SSZ versus MTX versus CsA	24 wks	42 versus 42 versus 42	ACR50	MTX is more efficacious than CSA and SSZ
Hamilton et al., 2001 [113]	Randomized open labeled trial	GST versus MTX	48 wks	72 versus 69	Paulus response criteria	GST and low dose MTX showed equivalent efficacy, but toxicity was more common in GST
Rau et al., 2002 [114]	Randomized double-blind controlled	GST versus MTX	156 wks	87 versus 87	Ratingen score	No differences in clinical efficacy and radiographic progression
Strand et al., 1999 [116]	Randomized double-blind controlled	LFN versus Placebo versus MTX	52 wks	182 versus 118 versus 182	ACR20	No differences in the efficacy of MTX versu LFN
Emery et al., 2000 [119]	Randomized double-blind controlled	LFN versus MTX	52 wks	501 versus 498	TJC, SJC, PhGA, PtGA	MTX is more efficacious than LEF, with low 2-yrs radiographic progression
Bao et al., 2003 [120]	Open randomized controlled	LFN versus MTX	24 wks	291 versus 213	ACR20	LFN is as effective but safer than MTX
Haagsma et al., 1997 [121]	Randomized double-blind controlled	SSZ versus MTX versus SSZ + MTX	52 wks	34 versus 35 versus 36	DAS	No differences in efficacy and radiographic progression between MTX and SSZ
Dougados et al., 1999 [122]	Randomized double-blind controlled	SSZ versus MTX versus SSZ + MTX	52 wks	68 versus 69 versus 68	DAS	No differences in efficacy and radiographic progression between MTX and SSZ
Capell et al., 2007 [123]	Randomized double-blind controlled	SSZ versus MTX versus SSZ + MTX	52 wks	55 versus 54 versus 56	DAS	No differences in efficacy and radiographic progression between MTX and SSZ
sDMARDs versus bDMARDs
Bathon et al., 2000 [16]	Randomized double-blind controlled	ETN 25 mg versus ETN 10 mg versus MTX	52 wks	207 versus 208 versus 217	ACR-N AUC (24 wks), mTSS (52 wks)	ETN had a more rapid rate of improvement than MTX
Jones et al., 2010 [125]	Randomized double-blind controlled	TCZ versus MTX	24 wks	288 versus 284	ACR20	TCZ monotherapy is more efficacious than MTX
Klareskog et al., 2004 [29]	Randomized double-blind controlled	ETN + MTX versus ETN Versus MTX	52 wks	231 versus 223 versus 228	ACR-N AUC (24 wks), mTSS (52 wks)	Combination therapy and ETN are more efficacious than MTX (combo > ETN).
Breedveld et al., 2006 [14]	Randomized double-blind controlled	ADA + MTX versus ADA versus MTX	104 wks	268 versus 274 versus 257	ACR50, mTSS	Combination therapy was superior to both mono-therapies. No differences between ADA and MTX.
bDMARDs versus bDMARDs
Gabay et al., 2013 [127]	Randomized double-blind controlled	TCZ versus ADA	24 wks	163 versus 162	DAS28	TCZ is superior to ADA
Weinblatt et al., 2012 [128]	Randomized double-blind controlled	ABT versus ADA	52 wks	318 versus 328	ACR20, mTSS	ABT is noninferior to ADA

sDMARDs: synthetic disease modifying antirheumatic drugs; LFN: leflunomide; SSZ; sulfasalazine; TJC: tender joint count; SJC: swollen joint count; ACR: American College of Rheumatology; HAQ: Health Assessment Questionnaire; AZA: azathioprine; MTX: methotrexate; VAS: visual anagogic scale; GST: gold sodium thiomalate; AUR: auranofin; MRI: magnetic resonance imaging; LOCF: last observation carried forward; HRQOL: health related quality of life, SF-36: 36-item short form health survey, DAS: disease activity score; CsA: cyclosporine A; ETN: etanercept; ACR-N AUC: numeric index of the ACR response area under the curve; ADA: adalimumab; TCZ: tocilizumab; and ABT: abatacept.