Table 2.
Characteristics of included trials
| Name of study | Type of study | Study phase | Population | Duration of enrollment | Intervention | Number of patients | Follow up duration | Countries | Number of centers | Treatment arms | Primary outcome | Secondary outcomes |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Burmester [18] | Double-blind | Phase 3 | RA with IR to TNF inhibitors | October, 2009 to March 2011 | Tofacitinib and placebo | 399 | 6 months | 13 countries including North America, Latin America and Europe | 82 | Tofacitinib 5 mg, 10 mg BID vs. placebo along with MTX | ACR 20, HAQ-DI | DAS28-ESR |
| Fleischman [20] | Double-blind | Phase 3/long term | RA with IR to MTX | NA | Upadactinib, placebo, adalimumab | 1629 | 48 weeks | 41 | 286 | Upadactinib 15 mg, adalimumab 40 mg, placebo | DAS28-CRP, ACR20, inhibition of radiographic progression | DAS28-CRP mean change of DAS28-CRP, HAQ DI, SF-36, PCS, FACIT-F, CDAI < 10 |
| Fleischman [19], RA-BEGIN | Double-blind | Phase 3 | RA with no or minimal csDMARDs and naive to bDMARDs | 01/13–08/14 | Barictinib, MTX or combination of Barictinib and MTX | 588 | 52 weeks | 18 counries | 198 | Baricitnib 4 mg, Baricitinib 4 mg + MTX | Noninferioritiy of baricitnib monotherapy to MTX monotherapy by ACR20 at 24 weeks | Superiority comparision by ACR 20, HAQ-DI, SDAI, DAS28-CRP, vdH-mTSS |
| Genovese [21] | Double-blind | Phase 2b | RA with IR to MTX | 03/14–07/15 | Upadacitinib, placebo | 300 | 12 weeks | 16 | 63 | Upadactinib 3 mg bid, 6 mg bid, 12 mg bid, 18 mg bid, 24 mg q day, placebo bid | ACR20 | ACR50, ACR70, DAS28-CRP, CDAI |
|
Van der Hejide [25] ORAL SCAN |
Double-blind | Phase 3 | Active RA with IR to MTX | NA | Tofacitinib vs. placebo | 797 | 24 months | NA | NA | Tofacitinib 5 mg, 10 mg BID vs. placebo | ACR20, ACR50, ACR70, mean changes in DAS28-ESR, CDAI, SDAI, HAQ-DI | NA |
| Kivitz [22] | Double blind | Phase 2b | Modearte to severe RA with IR to MTX | NA | Peficitinib | 378 | 12 weeks | (8) Usa, poland, hungary, Czech republic, Mexico, Bulgaria, Belgium, Colombia | 43 | Peficitinib 25, 50, 100, 150 mg | ACR20 using CRP at 12 weeks | ACR50, ACR70, DAS28-CRP, CDAI |
| Kremer [23] | Double blind | Phase 2b | RA with IR to MTX | 10/13–07/15 | Upadactinib, placebo, adalimumab | 276 | 12 weeks | 10 (North america, Europe, Australia) | 123 | Upadacitnib 3 mg, 6 mg, 12 mg, 18 mg | ACR20 | ACR50, ACR70, Low disease points/remission by DAS28-CRP, CDAI, Change in DAS28-CRP, ACR core set changes, MCID of HAQ DI |
| Li [24] | Double blind | Phase 3 | RA with IR to MTX | NA | Baricitinib, placebo | 290 | 52 weeks | 3 (China, Brazil, Argentina) | 30 | Baricitinib 4 mg | ACR 20 at 12 weeks | HAQ-DI, DAS28-CRP, remission and LDA, SDAI, CDAI, ACR50, ACR70 |
| Takeuchi [26] RAJ4 | Double blind | Phase 3 | RA pt with IR to MTX | July 2014-Nov 2017 | Peficitinib | 519 | 52 weeks | Japan | 161 | Peficitinib 100 mg, 150 mg | ACR20 at 12 weeks/ET, baseline change in mTSS at 28 weeks/ET | ACR20/50/70 response, DAS28-CRP, DAS28-ESR, CRP, ESR, PGA, TJC68, SJC66, CDAI, SDAI |
| Tanaka [27] | Double-blind | Phase 2b | pt with moderate to severe RA on MTX | 11/11–12/13 | Baricitinib, placebo | 145 | 12 weeks | Japan | 24 | Baricitinib 1 mg, 2 mg, 4 mg, 8 mg | ACR20 at 12 weeks/ET, baseline change in mTSS at 28 weeks/ET | ACR50, ACR70, ACR core components, DAS28-ESR, DAS28-CRP, SDAI, EULAR28 |
| Taylor [28] | Double-blind | Phase 3 | pt with RA on MTX | 11/12–09/14 | Baricitinib 4 mg, adalimumab 40q2wk | 1307 | 52 weeks | 26 | 281 | Baricitinib 4 mg, adalimumab 40q2wk | ACR20 at 12 weeks, | mTSS score at 24 weeks, HAQDI, DAS28-CRP, SDAI, PRO at week 12 |
|
Vollenhoven [29] ORAL standard study |
Double blind | Phase 3 | RA pt with IR to MTX | 01/09–02/11 | Tofacitinib, adalimumab, placebo | 717 | 12 months | Worldwide | 115 | Tofacitinib 5 mg, 10 mg twice daily, 40 mg of adalimumab q2wks, placeebo | ACR20 reduction in tender and swollen joints at 6 months, 3/5ACR components, HAQ-DI at 3 months, DAS28-ESR | ACR20, ACR50, ACR70 with respect to tender and swollen joints and HAQ-DI |
| Westhovens [30] DARWIN 1 | Double blind | Phase 2b | Active RA with insufficient response to MTX | July 2013 to May 2015 | Filgotinib vs. placebo in combination with MTX | 594 | 24 weeks | 21 (North and South America, Europe, Asia, Australia) | 106 | Filgotinib 50 mg, 100 mg, 200 mg once or twice daily vs. placebo | ACR20 at 12 weeks | ACR20, ACR50, ACR70, ACR-N, DAS28-CRP, LDA/remission, EULAR response, EULAR remission, CADI, SDAI |
ACR American college of rheumatology, CRP C-reactive protein, CDAI clinical disease activity index, DAS28 disease activity score 28, ESR erythrocyte sedimentation rate, EULAR European League Against Rheumatism, FACIT-F functional assessment of chronic illness therapy fatigue scale, HAQ-DI health assessment questionnaire disability index, IR inadequate response, LDA low disease activity, MCID minimum clinically important difference, MTX methotrexate, NA not available, PCS physical component score, PGA physician’s global assessment of disease activity, PRO patient reported outcomes, RA rheumatoid Arthritis, SF-36 short-form 36, SDAI simplified disease activity index, SJC swollen joint count, TNF-alpha tumor necrosis factor-alpha, TJC total joint count, vdH-mTSS van der Heijde-modified total sharp score