. 2016 Jun 10;7:11849. doi: 10.1038/ncomms11849

Table 2. Unique differentially methylated pathways between RA knee and hip FLS.

Unique RA-knee versus RA-hip pathways	-log (P-value)	Ratio	Drug targets	Drugs
IL-17A signalling in airway cells	1.98	0.08	IL-6, JAK1, JAK2, JAK3, p38 MAPK, IL-17A, NFkB, PI3K, MEK1/2	Tocilizumab^, sirukumab^†, MEDI5117^†, ALX-0061^†, sarilumab^†, olokizumab^†, tofacitinib^, baracitinib^†, peficitnib^†, ruxolitinib^†, INCB39110^†, CYT387^†, filgotinib^†, PF-956980^†, decernotinib^†, R-348^‡, PH-797804^‡, BMS-582949^‡, ARRY-371797^‡, dilmapimod^‡, VX-702^‡, pamapimod^‡, VX-745^‡, talmapimod^‡, AMG-548^‡, doramapimod^‡, secukinumab^†, ixekizumab^†, brodalumab^†, iguratimod^† (approved in China and Japan), CAL-263^†, duvelisib^‡, idelalisib^‡, ARRY-162^‡, PD98059^‡, AZD8055^‡
IL-22 signalling	1.87	0.13	JAK1, Tyk2, p38 MAPK, ERK1/2	Tofacitinib^*, baracitinib^†, peficitnib^†, ruxolitinib^†, INCB39110^†, CYT387^†, filgotinib^†, fezakinumab^‡, PH-797804^‡, BMS-582949^‡, ARRY-371797^‡, dilmapimod^‡, VX-702^‡, pamapimod^‡, VX-745^‡, talmapimod^‡, AMG-548^‡, doramapimod^‡, ARRY-162^‡, PD98059^‡, AZD8055^‡
Role of JAK family kinases in IL-6-type cytokine signalling	1.82	0.12	IL-6, JAK1, JAK2, Tyk2, p38 MAPK, ERK1/2	Tocilizumab^, sirukumab^†, MEDI5117^†, ALX-0061^†, sarilumab^†, olokizumab^†, tofacitinib^, baracitinib^†, peficitnib^†, ruxolitinib^†, INCB39110^†, CYT387^†, filgotinib^†, fezakinumab^‡, PH-797804^‡, BMS-582949^‡, ARRY-371797^‡, dilmapimod^‡, VX-702^‡, pamapimod^‡, VX-745^‡, talmapimod^‡, AMG-548^‡, doramapimod^‡, ARRY-162^‡, PD98059^‡, AZD8055^‡
p53 signalling	1.82	0.06	p38 MAPK, PI3K	PH-797804^‡, BMS-582949^‡, ARRY-371797^‡, dilmapimod^‡, VX-702^‡, pamapimod^‡, VX-745^‡, talmapimod^‡, AMG-548^‡, doramapimod^‡, CAL-263^†, duvelisib^‡, idelalisib^‡
IL-17 signalling	1.77	0.07	IL-6, COX2, JAK1, JAK2, p38 MAPK, PI3K, iNOS, MEK1/2, CRP, CXCL10	Tocilizumab^, sirukumab^†, MEDI5117^†, ALX-0061^†, sarilumab^†, olokizumab^†, NSAIDs^, tofacitinib^*, baracitinib^†, peficitnib^†, ruxolitinib^†, INCB39110^†, CYT387^†, filgotinib^†, PH-797804^‡, BMS-582949^‡, ARRY-371797^‡, dilmapimod^‡, VX-702^‡, pamapimod^‡, VX-745^‡, talmapimod^‡, AMG-548^‡, doramapimod^‡, CAL-263, duvelisib^‡, idelalisib^‡, GW274150 ^‡, ARRY-162^‡, PD98059^‡, AZD8055^‡, ISIS-CRP^‡, eldelumab^‡
2-Amino-3-carboxymuconate semialdehyde degradation to glutaryl-CoA	1.68	1.00	NA	NA
Retinoate biosynthesis I	1.55	0.07	NA	NA
Inhibition of angiogenesis by TSP1	1.53	0.09	p38 MAPK	PH-797804^‡, BMS-582949^‡, ARRY-371797^‡, dilmapimod^‡, VX-702^‡, pamapimod^‡, VX-745^‡, talmapimod^‡, AMG-548^‡, doramapimod^‡
TGF-β signalling	1.46	0.06	p38 MAPK, MEK1/2	PH-797804^‡, BMS-582949^‡, ARRY-371797^‡, dilmapimod^‡, VX-702^‡, pamapimod^‡, VX-745^‡, talmapimod^‡, AMG-548^‡, doramapimod^‡, ARRY-162^‡, PD98059^‡, AZD8055^‡
Acute phase response signalling	1.3	0.04	TNF, IL-1, GCR, IL-6, p38 MAPK, JAK2, CRP, C5a, mTOR, NFkB, PI3K, MEK1/2	Etanercept^, infliximab^, adalimumab^, certolizumab pegol^, golimumab^, SSR150106, anakinra^, canakinumab^†, GSK1827771^‡, corticosteroids^, tocilizumab^, sirukumab^†, MEDI5117^†, ALX-0061^†, sarilumab^†, olokizumab^†, PH-797804^‡, BMS-582949^‡, ARRY-371797^‡, dilmapimod^‡, VX-702^‡, pamapimod^‡, VX-745^‡, talmapimod^‡, AMG-548^‡, doramapimod^‡, baracitinib^†, ruxolitinib^†, CYT387^†, ISIS-CRP^‡, NN 8209^‡, NN 8210^‡, eculizumab^‡, MP-435^‡, temsirolimus^†, iguratimod^† (approved in China and Japan), CAL-263^†, duvelisib^‡, idelalisib^‡, ARRY-162^‡, PD98059^‡, AZD8055^‡
Death receptor signalling	1.3	0.03	TNF, NFkB	Etanercept^, infliximab^, adalimumab^, certolizumab pegol^, golimumab^*, SSR150106^†, iguratimod^† (approved in China and Japan)

FLS, fibroblast-like synoviocyte; NA, not applicable; RA, rheumatoid arthritis; NA, not applicable; Ratio, number of DMGs divided by the total number of genes in the pathway.

^*Currently approved in the USA for RA.

^†In clinical development at the time of publication.

^‡Discontinued.