JAK Inhibitors in Psoriatic Disease

Figures & data

Table 1 JAK Inhibitors in Psoriatic Disease

Drug; Trial	Trial Description/Duration	Patients	Efficacy	AEs; Discontinuation for AEs
Tofacitinib; NCT00678210^Citation65	Phase IIb, randomized placebo-controlled, dose-ranging study / 12 weeks	197 pts Randomization to: PBO: 50 Tofacitinib 2mg BID: 49 Tofacitinib 5mg BID: 49 Tofacitinib 15mg BID: 49	At week 12, PASI75 response rates were significantly higher for all tofacitinib groups: 25.0% (2mg; p<0.001), 40.8% (5mg; p<00001) and 66.7% (15mg; p<0.0001), compared with placebo (2.0%)	Therapy-arm group: 115 (58.4%); 9 (4.6%) Placebo: 30 (60.0%); 3 (6.0%) Most frequent AEs: upper respiratory tract infection, nasopharyngitis and headache.
Tofacitinib; OPT Pivotal 1^Citation66	Phase II, randomized placebo-controlled / 16 weeks	900 pts Randomization to: PBO: 177 Tofacitinib 5mg BID: 360 Tofacitinib 10mg BID: 363	At week 16, PGA response* rates in tofacitinib 5mg group and 10mg group were 152 (41.9%) and 213 (59.2%), respectively, significantly higher than placebo: 16 (9.0%) (<0.001 vs placebo in both groups) PASI75 response rates were significantly higher for all tofacitinib groups: 145 (39.9%; 5mg; p<0.001), 213 (59.2% (10mg; p<001), compared with placebo (11, 6.2%)	Therapy-arm group: 494 (54.9%); 33 (3.7%) Placebo: 90 (50.8%); 11 (6.2%) Most frequent AEs: nasopharyngitis and upper respiratory tract infection
Tofacitinib; OPT Pivotal 2^Citation66	Phase II, randomized placebo-controlled / 16 weeks	951 pts Randomization to: PBO: 196; Tofacitinib 5mg BID: 382 Tofacitinib 10mg BID: 381	At week 16, PGA response* rates in tofacitinib 5mg group and 10mg group were 173 (46.0%) and 221 (59.1%), respectively, significantly higher than placebo: 21 (10.9%) (P < 0.001 vs placebo in both groups) PASI75 response rates were significantly higher for all tofacitinib groups: 173 (46.0%; 5mg; p<0.001), 223 (59.6% (10mg; p<001), compared with placebo (22, 11.4%).	Therapy-arm group: 518 (54.5%); 30 (3.1%) Placebo: 93 (47.4%); 6 (3.1%) Most frequent AEs: nasopharyngitis and upper respiratory tract infection.
Tofacitinib; NCT01241591^Citation67	Phase II, randomised, multicentre, double-dummy, placebo-controlled, non-inferiority trial / 12 weeks	1101 pts Randomization to PBO: 107; Tofacitinib 5mg BID: 329; Tofacitinib 10mg BID: 330; Etanercept 50mg twice weekly: 335	At week 12, the proportions of PGA responders were 155 (47.1%), 225 (68.2%), 222 (66.3%) and 16 (15.0%) in the tofacitinib 5mg group, tofacitinib 10mg group, etanercept group, and placebo group, respectively PASI75 response was reached by 130 (39.5%), 210 (63.6%), 197 (58.8%) and 6 (5.6%) subjects of the same groups, respectively. For both coprimary endpoints, tofacitinib 10mg BID was non-inferior to etanercept and was superior to placebo, whereas tofacitinib 5mg BID did not meet the non-inferiority criteria versus etanercept but met the superiority criteria versus placebo.	Therapy-arm group: 625 (56.8%); 28 (2.5%) Placebo: 55 (51.4%); 4 (3.7%) Etanercept 50mg twice weekly: 192 (57.3%); 11 (3.3%) Most frequent AEs: nasopharyngitis and upper respiratory tract infection
Itacitinib; NCT01634087^Citation68	Phase II, randomized, double-blind, placebo-controlled, dose-escalation study / 4 weeks	50 pts Randomization to PBO: 12 Itacitinib 100mg QD: 9 Itacitinib 200mg QD: 9 Itacitinib 200mg BID: 9 Itacitinib 600mg QD: 11	At week 4, a mean percentage reduction from baseline in sPGA of 22.2%, 29.4%, 35.2% 42.4% and 12.5% for 100mg QD (p =0.270 vs placebo), 200mg QD (p = 0.118), 200mg BID (p = 0.053), 600mg QD (p = 0.003) and placebo cohort was observed, respectively	Therapy-arm group: 23 (46.0%); 0 Placebo: 4 (33.3%); 0 Most frequent AEs: nasopharyngitis, increased aspartate aminotransferase, headache and hypertriglyceridemia
Abrocitinib; NCT02201524^Citation69	Phase II, randomized, double-blind, placebo-controlled study / 4 weeks	59 pts Randomization to PBO: 14 Abrocitinib 200mg QD: 15 Abrocitinib 400mg QD: 16 Abrocitinib 200mg BID: 14	At week 4, PASI75 was reached by 17%, 17%, 50% and 60% of patients receiving placebo, abrocitinib 200mg QD, abrocitinib 400mg QD and 200mg BID, respectively	Therapy-arm group: 26 (44.1%); 3 (5.1%) Placebo: 3 (21.4%); 0 Most frequent AEs: nausea and headache
Solcitinib; NCT01782664^Citation70	Phase IIa, randomized, placebo-controlled study / 12 weeks	60 pts Randomization to: PBO: 15 Solcitinib 100mg BID: 15 Solcitinib 200mg BID: 15 Solcitinib 400mg BID: 14	At week 12, PASI 75 response was 0% in the placebo group compared with 13%, 25% and 57% in the 100mg, 200mg and 400mg solcitinib BID cohort, respectively	Total AEs: NR Discontinuation for AEs: NR Most frequent AEs: headache, nasopharyngitis, nausea, diarrhoea, fatigue and upper abdominal pain
Baricitinib; NCT01490632^Citation71	Phase IIb, randomized, double-blind, multicountry, placebo-controlled, dose-ranging study / 12 weeks	271 pts Randomization to: PBO: 34 Baricitinib 2mg QD: 32 Baricitinib 4mg QD: 72 Baricitinib 8mg QD: 64; Baricitinib10mg QD: 69	At week 12, all baricitinib treated groups showed greater mean changes from baseline in their PASI scores (p<0.05) and (except 2mg) a higher rate of PASI50 than the placebo group Moreover, statistically significant PASI90 responses were achieved in the 8mg and 10mg groups at 8 and 12 weeks	Therapy-arm group: 146 (53.9%); 10 (3.7%) Placebo: 15 (44.1%); 0 (0%) Most frequent AEs: nasopharyngitis, infections
Peficitinib; NCT01096862^Citation72	Phase IIa, randomized, double-blind, placebo-controlled, sequential dose-escalation study / 6 weeks	124 pts Randomization to: PBO: 29 Peficitinib 10mg BID: 19 Peficitinib 25mg BID: 21 Peficitinib 60mg BID: 19 Peficitinib 100mg BID: 17 Peficitinib 50mg QD: 19	At week 6, PASI75 response was achieved by 5 (17.2%), 12 (63.2%), 10 (47.6%), 13 (68.4%), 13 (76.5%), 13 (76.5%), 9 (47.4%) patients receiving placebo, peficitinib 10mg BID, peficitinib 25mg BID, peficitinib 60mg BID, peficitinib 100mg BID, and peficitinib 50mg QD, respectively	Therapy-arm group: 55 (44.3%); 3 (2.4%) Placebo: 11 (37.9%); 0 Most frequent AEs: nasopharyngitis, diarrhoea, acne, back pain, and contact dermatitis
Deucravacitinib; NCT02931838^Citation73	Phase II, randomized, double-blind trial / 12 weeks	237 pts Randomization to: PBO: 45 Deucravacitinib 3mg QD: 44 Deucravacitinib 3mg BID: 44 Deucravacitinib 3mg BID: 45 Deucravacitinib 6mg BID: 45 Deucravacitinib 12mg QD: 44.	At week 12, PASI75 was achieved by 3 (6.7%), 4 (9.1%), 17 (38.6%), 31 (68.9%), 30 (66.7%) and 33 (75.0%) patients, respectively, with a statistical significance in the 3mg QD, 3mg BID, 6mg BID, and 12mg QD cohort (p<0.001 vs placebo for all)	Therapy-arm group: 172 (64.4%); 10 (3.7%) Placebo: 23 (51.1%); 2 (4.4%) Most frequent AEs: nasopharyngitis, headache, diarrhoea
Deucravacitinib; POETYK PSO-1^Citation74	Phase II, randomized, double-blind, placebo-controlled / 16 weeks	666 pts Randomization to: PBO: 166 Deucravacitinib 6mg QD: 332 Apremilast 30mg BID: 168	At week 16, 194 (58.4%) patients reached PASI75 in the deucravacitinib group compared with 21 (12.7%) in the placebo cohort (p<0.0001) and 59 (35.1%) in the apremilast group (p<0.0001)	Therapy-arm group: 339 (50.9%); 23 (3.5%) Placebo: 70 (42.2%); 7 (4.2%) Apremilast 30mg BID: 93 (55.4%); 10 (6.0%) Most frequent AEs: nasopharyngitis, headache, diarrhoea, upper respiratory tract infection
Deucravacitinib; POETYK PSO-2^Citation75	Phase II, randomized, double-blind, placebo-controlled / 16 weeks	1020 pts Randomization to: PBO: 255 Deucravacitinib 6mg QD: 511 Apremilast 30mg BID: 254	At week 16, 271 (53.0%) patients reached PASI75 at week 16 (primary outcome) in the deucravacitinib group compared with 24 (9.4%) in the placebo cohort (p<0.0001) and 101 (39.8%) in the apremilast group (p=0.0004)	Therapy-arm group: 581 (57.0%); 35 (3.4%) Placebo: 138 (54.1%); 9 (3.5%) Apremilast 30mg BID: 150 (59.1%); 12 (4.7%) Most frequent AEs: nasopharyngitis, headache, diarrhoea, upper respiratory tract infection
Brepocitinib; NCT02969018^Citation76	Phase IIa, randomized, double-blind, placebo-controlled trial / 4 weeks	212 pts Randomization to PBO: 23 Brepocitinib 30mg QD: 84 Brepocitinib 60mg QD: 105 At week 12: Brepocitinib 60 to 30mg QD: 25 Brepocitinib 60 to 10mg QD: 29 Brepocitinib 60 to 100mg QW: 26 Brepocitinib 60 to PBO: 25 Brepocitinib 30mg QD: 29 Brepocitinib 30 to 10mg QD: 25 Brepocitinib 30 to 100mg QW: 30 PBO: 23	At week 4, PASI reductions were similar in both the brepocitinib 60mg and 30mg induction dose groups. At week 12, PASI reductions were observed in all active treatment groups and were statistically significant compared with placebo in the 60 to 30mg QD treatment group, 60mg QD to 100mg once weekly treatment group, 30mg QD treatment group, 30- to 10mg QD treatment group, and 30mg QD to 100mg once weekly treatment group	Therapy-arm group: 149 (70.3%); 13 (6.1%) Placebo: 13 (56.5%); 0 Most frequent AEs: nasopharyngitis, upper respiratory tract infection
Ropsacitinib; NCT03895372^Citation77	Phase IIb, randomized, double-blind, placebo controlled, parallel-group study / 16 weeks	178 pts Randomization to: PBO: 45 Ropsacitinib 50mg QD: 22 Ropsacitinib 100mg QD: 23 Ropsacitinib 200mg QD: 45 Ropsacitinib 400mg QD: 43	At week 16, a significantly greater proportion of participants achieved PASI90 (risk difference percentage) in the 200mg and 400mg groups (33.0%, p = 0.0004 and 46.5%, p<0.0001, respectively) versus placebo	Therapy-arm group: 109 (61.2%); 9 (5.1%) Placebo group: 23 (51.1%); 1 (2.2%) Most frequent AEs: nasopharyngitis, upper respiratory tract infection, and higher blood pressure

Abbreviations: AE, adverse event; BSA, body surface area; Pt, patient; QD, once a day; BID, two times a day; QW, once a week; PBO, placebo.

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