Table 1

Randomised controlled trials included for review

Patients population	Trial name	References	RA classfication criteria	ClinicalTrials.gov number	Enrollment start date*	Active drug	Comparator drug	Number of patients per treatment arm comparator-active†
MTX naïve	US301/ULTRA	¹¹	1987	–	1995	LEF	PBO, MTX	118–182
	MN302‡	¹¹	1987	–	1994	LEF	MTX	487–498
	ERA	¹²	1987	–	May 1997	ETN	MTX	217–208
	ASPIRE§	¹³	1987	–	July 2000	IFX	MTX	282–363
	PREMIER¶	¹⁴	1987	–	December 2000	ADA	MTX	257–274
	COMET‡	¹⁵	1987	NCT00195494	October 2004	ETN	MTX	263–265
	GO-BEFORE§, ¶	¹⁶	1987	NCT00264537	December 2005	GOL	MTX	160–159
	IMAGE	¹⁷	1987	NCT00299104	January 2006	RTX	MTX	249–250
	OPTIMA‡, **	¹⁸	1987	NCT00420927	December 2006	ADA	MTX	517–515
	AGREE‡,§	¹⁹	1987	NCT00122382	2005*	ABA	MTX	253–256
	HOPEFUL 1	²⁰	1987	NCT00870467	March 2009	ADA	MTX	163–171
	FUNCTION	²¹	1987	NCT01007435	October 2009	TCZ	MTX	287–292
	PRIZE‡, **	²²	1987	NCT00913458	October 2009	ETN	PBO, MTX	65–65
	ORAL Start	²³	1987	NCT01039688	January 2010	TOF	MTX	186–397
	C-OPERA‡, **	²⁴	2010	NCT01451203	October 2011	CZP	MTX	157–159
	C-EARLY‡, **, ††	²⁵	2010	NCT01519791‡‡	January 2012	CZP	MTX	213–655
	RA-BEGIN§, ¶, ††	²⁶	2010	NCT01711359	January 2013	BAR	MTX	210–215
MTX IR	European IL-1Ra§§	²⁷	1987	–	–	ANA	PBO	116–121
	ATTRACT	²⁸	1987	–	March 1997	IFX	MTX	88–87
	DE-O19	²⁹	1987	–	February 2000	ADA	MTX	200–212
	AIM	³⁰	1987	NTC00048568	November 2002	ABA	MTX	219–433
	LITHE‡, ¶¶	³¹	1987	NCT00106535	December 2004	TCZ	MTX	393–399
	RAPID 1	³²	1987	NCT00152386	February 2005	CZP	MTX	199–393
	RAPID 2¶¶	³³	1987	NCT00175877	June 2005	CZP	MTX	127–246
	GO-FORWARD	^{34 35}	1987	NCT00264550	November 2005	GOL	MTX	133–133
	GO-FORTH	³⁶	1987	NCT00727987	May 2008	GOL	MTX	88–87
	CAMEO**	³⁷	1987	NCT00654368	June 2008	ETN	MTX	104–94
	J-RAPID¶¶	³⁸	1987	NCT00791999	November 2008	CZP	MTX	77–85
	ACT-RAY‡, ¶, **	³⁹	1987	NCT00810199	March 2009	TCZ	MTX	276–277
	ORAL-SCAN¶¶	⁴⁰	1987	NCT00847613	March 2009	TOF	PBO	79–321
	GO-FURTHER	⁴¹	1987	NCT00973479	September 2009	GOL	MTX	197–395
	AMPLE***	⁴²	1987	NCT00929864	October 2009	ABA	ADA	328–318
	DRIVE	⁴³	1987	JapicCTI-101 263	August 2010	DNM	MTX	88–87
	PLANETRA†††	⁴⁴	1987	NCT01217086	October 2010*	CPT13	IFX	304–302
	MOBILITY¶¶	⁴⁵	1987	NCT01061736	March 2011	SAR	MTX	398–400
	RA-BEAM ***	⁴⁶	2010	NCT01710358	November 2012	BAR	MTX	488–487
	SB4§§, †††	⁴⁷	2010	NCT01895309	June 2013*	SB4	ETN	297–299
	SB2§§, †††	⁴⁸	2010	NCT01936181	August 2013*	SB2	IFX	293–291
	RAJ4	⁴⁹	2010	NCT02305849	July 2014*	PEF	MTX	170–175
	SELECT-COMPARE ***	⁵⁰	2010	NCT02629159	December 2015*	UPA	MTX	651–651
DMARDs IR	MN301	¹¹	1987	–	1994	LEF	PBO, SSZ	91–134
	TEMPO¶	⁵¹	1987	–	October 2000	ETN	MTX	228–231
	SAMURAI	⁵²	1987	–	March 2003	TCZ	DMARDs	148–158
	GO-MONO	⁵³	1987	–	May 2008	GOL	PBO	105–102
	HIKARI‡	⁵⁴	1987	NCT00791921‡‡‡	November 2008	CZP	DMARDs§§§	114–116
	J-ETA§§	⁵⁵	1987	–	–	ETN	MTX	176–192
	BREVACTA¶¶	⁵⁶	1987	NCT01232569	March 2011	TCZ	DMARDs	219–437
	SURROUND-D	⁵⁷	2010	NCT01604343	July 2012	SIR	DMRADs	556–557
	RA-BUILD	⁵⁸	2010	NCT01721057	January 2013	BAR	DMARDs	228–229
TNFi IR	REFLEX	⁵⁹	1987	NCT00468546	July 2003	RTX	MTX	209–308
	ADMIRE**	⁶⁰	1987	NCT00808509	January 2009	ADA	MTX	16–17
	REASSURE	⁶¹	2010	NCT01377012	August 2011*	SEC	MTX	214–213

*If the patient’s enrollment date could not be confirmed in the paper, it was replaced by the trial start date from the ClinicalTrials.Gov site.
†If the trial had multiple arms, the active drug group including the largest population of patients was marked as active in the table.
‡If the trial had multiple investigation periods/phases, the data for period/phase-1 or double-blind period data were only recorded.
§This trial permitted MTX user who had not received it more than 3 weekly.
¶This trial included a comparative study between monotherapy and combination therapy.
**This trial included a withdrawal or tapering study of active drug.
††DMARD-naïve patients were included.
‡‡This trial had two periods. In the case of withdrawal study period, the clinical trial number is NCT01521923.
§§This was not a trial name.
¶¶This trial included biological DMARDs user.
***This trial included a head to head study.
†††This was a non-inferiority trial of biosimilar drug.
‡‡‡This trial had two periods. In the case of open-label period, the clinical trial number is NCT00791921.
§§§DMARDs, other than MTX and leflunomide, were defined as comparator drugs.
ABA, abatacept; ADA, adalimumab; ANA, anakinra; BAR, baricitinib; CT-P13, biosimilar of infliximab; CZP, certolizumab; DNM, denosumab; DMARDs, disease-modifying antirheumatic drugs; ETN, etanercept; GOL, golimumab; IFX, infliximab; IR, inadequate responder; LEF, leflunomide; MTX, methotrexate; NR, not reported; PBO, placebo; PEF, peficitinib; RA, rheumatoid arthritis; RTX, rituximab; SAR, sarilumab; SB2, biosimilar of infliximab; SB4, biosimilar of etanercept; SEC, secukinumab; SIR, sirukumab; TCZ, tocilizumab; TNF, tumor necrosis factor; TOF, tofacitinib; UPA, upadacitinib.