Tofacitinib versus etanercept or placebo in patients with moderate to severe chronic plaque psoriasis: patient-reported outcomes from a Phase 3 study

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1 DOI: /jdv.1372 JEADV ORIGINAL ARTICLE Tofacitiib versus etaercept or placebo i patiets with moderate to severe chroic plaque psoriasis: patiet-reported outcomes from a Phase 3 study F. Valezuela, 1, C. Paul, 2 L. Mallbris, 3, H. Ta, 4 J. Papacharalambous, 4 H. Valdez, 5 C. Mamolo 4 1 Departmet of Dermatology, Faculty of Medicie, Uiversity of Chile ad Probity Medical Research, Satiago, Chile 2 Toulouse Uiversity ad Larrey Hospital, Toulouse, Frace 3 Pfizer Ic, Collegeville, PA, USA 4 Pfizer Ic, Groto, CT, USA 5 Pfizer Ic, New York, NY, USA Correspodece: F. Valezuela. fvalezuela.cl@gmail.com Abstract Backgroud Tofacitiib is a oral Jaus kiase ihibitor that is beig ivestigated for psoriasis. Psoriasis impacts o physical ad psychological well-beig; improvemets i health-related quality of life (HRQoL) with etaercept i psoriasis are well documeted. Objective To evaluate HRQoL with tofacitiib, vs. placebo or etaercept, i the Phase 3, radomized, placebocotrolled, o-iferiority, Oral-treatmet Psoriasis Trial (OPT) Compare Study (NCT ). Methods Adults with moderate to severe chroic plaque psoriasis were radomized 3:3:3:1 to tofacitiib 1 or 5 mg twice daily (BID), etaercept 5 mg twice weekly or placebo, for 12 weeks. Patiet-reported outcomes (PROs) icluded Dermatology Life Quality Idex (DLQI), Itch Severity Item ad Patiet Global Assessmet of psoriasis. Results At baselie, 83.4% (911/192) of patiets had a DLQI score ragig betwee 6 ad 3, idicatig a substatial burde of disease. By 12, 47.3%, 43.6% ad 3.9% of patiets i the tofacitiib 1 mg BID, etaercept ad tofacitiib 5 mg BID groups, respectively, had a DLQI score of or 1 (o effect of psoriasis o QoL) vs. 7.8% for placebo (all P <.1). Tofacitiib sigificatly reduced itch vs. placebo (P <.5 both doses) ad etaercept (P <.1 both doses) withi 1 day of startig treatmet. Furthermore, reductios i itch were greater with tofacitiib 1 mg BID, vs. etaercept, at s 2 12 (all time poits P <.5). At 2, a Itch Severity Item score of little or o itch was more frequet with tofacitiib 1 mg (68.6%) vs. etaercept (57.4%) ad placebo (12.2%), ad the PtGA respose rate was sigificatly greater with tofacitiib 1 mg vs. placebo (P <.5). Coclusio Oral tofacitiib provided sigificat improvemets across multiple PROs by 12. Improvemets with tofacitiib 1 mg BID were comparable to etaercept, ad improvemets i itch were greater ad more rapid with tofacitiib 1 mg BID. Received: 23 October 215; Accepted: 8 March 216 Coflicts of iterest F.V. has bee a pricipal ivestigator, member of a scietific advisory board or speaker for AbbVie, Jasse, Eli-Lilly, Merck, Novartis ad Pfizer Ic. C.P. has bee a cosultat or ivestigator for AbbVie, Amge, Boehriger, Celgee, Eli-Lilly, Jasse-Cilag, Novartis ad Pfizer Ic. H.T., J.P., H.V. ad C.M. are employees ad stockholders of Pfizer Ic. L.M. was a employee ad stockholder of Pfizer Ic at the time of the aalysis. Fudig sources This work was supported by Pfizer Ic. Itroductio Moderate to severe plaque psoriasis has a recogized impact o the physical ad emotioal well-beig of patiets. 1 Some existig treatmets for plaque psoriasis ca achieve a 75% Affiliatio at the time of the aalysis. reductio i Psoriasis Area Severity Idex (PASI75 respose) i over half of patiets. 2 4 However, such cliical efficacy edpoits do ot reflect the complete patiet experiece. For example, itch is a major symptom of psoriasis ad is kow to egatively impact the health-related quality of life (HRQoL). 5,6 I additio, JEADV 216, 3, The Authors. Joural of the Europea Academy of Dermatology ad Veereology published by Joh Wiley & Sos Ltd o behalf of Europea Academy of Dermatology ad Veereology. This is a ope access article uder the terms of the Creative Commos Attributio-NoCommercial-NoDerivs Licese, which permits use ad distributio i ay medium, provided the origial work is properly cited, the use is o-commercial ad o modificatios or adaptatios are made.

2 1754 Valezuela et al. patiets with psoriasis ofte suffer from impaired physical ad/ or metal health. 7,8 Thus, despite a variety of cliically efficacious therapeutic optios, treatmet dissatisfactio remais commo i patiets with psoriasis. 9 I order to improve the patiet experiece, a more holistic approach to outcomes assessmet is required, which ecompasses patiet-reported outcomes (PROs) as well as physicia efficacy assessmet. Thus, cliical evaluatio of treatmet efficacy i psoriasis should iclude measures that evaluate the totality of symptoms ad patiet perceptios. Etaercept, a biologic aget, has show improvemets i patiet-reported measures of HRQoL i psoriasis. 1 However, head-to-head studies that compare cliical efficacy ad PROs with a oral small-molecule aget vs. a biologic aget i the psoriasis settig are limited. 11,12 Tofacitiib is a oral Jaus kiase ihibitor that is beig ivestigated for psoriasis. I the Phase 3 Oral-treatmet Psoriasis Trial (OPT) Compare Study, tofacitiib 1 mg twice daily (BID) demostrated o-iferiority to etaercept 5 mg twice weekly (BIW) ad superiority to placebo, with regard to PASI75 ad Physicia Global Assessmet (PGA), at 12. No-iferiority to etaercept was ot demostrated for tofacitiib 5 mg BID. Both tofacitiib (5 ad 1 mg BID) ad etaercept were well tolerated. 13 Specific HRQoL data were collected durig the OPT Compare Study 13 ad are beig preseted here, separately from the primary efficacy results, to allow for a more detailed assessmet ad discussio. The objective of the preset aalysis was to examie the impact of tofacitiib (a orally admiistered small molecule) compared with etaercept (a established, frequetly used biologic) or placebo o PROs ad HRQoL i patiets with moderate to severe psoriasis, usig data from the Phase 3 OPT Compare Trial. Materials ad methods Study desig, patiets ad treatmet The study desig ad methods have bee described previously (cliicaltrials.gov; NCT ). 13 Briefly, the OPT Compare Study was a Phase 3, radomized, double-blid, double-dummy, placebo-cotrolled, active comparator study i adult patiets with moderate to severe chroic plaque psoriasis (duratio 12 moths) ad with a PASI score of 12 or higher, a PGA score of moderate or severe (o a five-poit severity scale of: clear ; 1 almost clear ; 2 mild ; 3 moderate ; 4 severe ) ad at least 1% affected body surface area. Patiets had failed to respod, had cotraidicatio or were itolerat to at least oe covetioal systemic psoriasis therapy. Patiets were radomized (3 : 3 : 3 : 1) to receive oral tofacitiib 5 or 1 mg BID, subcutaeous etaercept 5 mg BIW or placebo (matched dosig schedule) for 12 weeks, with a additioal 2- to 4-week follow-up period after the ed of the treatmet. Primary edpoits icluded the proportio of patiets achievig PASI75 at 12 ad the proportio of patiets achievig a PGA score of clear or almost clear at 12. PROs were evaluated as secodary edpoits. Assessmet of patiet-reported outcomes The Dermatology Life Quality Idex (DLQI) is a 1-item questioaire that assesses the impact of chroic ski coditios o HRQoL. Higher scores idicate greater impairmet. 14 The DLQI was measured at Day 1 (baselie), 4 ad 12. I additio to the PASI75 edpoit, a composite edpoit of PASI75 or 5 75% reductio from baselie i PASI (PASI5 75) ad DLQI score 5, used i psoriasis guidelies as a threshold to determie treatmet cotiuatio, 15 was also evaluated at 4 ad 12. Each patiet made a daily assessmet of itch severity usig the validated Itch Severity Item (ISI); 16 this was recorded i a diary each eveig (cocurret with the eveig dose of study drug) from 1 week before baselie to Day 15 postbaselie. Thereafter, ISI was assessed i the cliic at s 2, 4, 8 ad 12 (or the ed of treatmet). With the ISI, patiets rated the severity of itch due to psoriasis durig the previous 24 h usig a umeric ratig scale, where idicated o itch ad 1 idicated worst possible itch. Patiets evaluated their overall cutaeous disease usig the Patiet Global Assessmet of psoriasis (PtGA), which was assessed o Day 1 (baselie) ad at s 2, 4, 8 ad 12 (or the ed of treatmet) usig a sigle-item, five-poit scale. Category labels were the same as for the PGA: severe, moderate, mild, almost clear, ad clear (o psoriasis). PtGA respose was defied as clear or almost clear. The Short-Form Health Survey (SF-36) versio 2 acute form measures health status by assessig eight domais of fuctioal health ad well-beig: physical fuctioig, role limitatios due to physical health problems, bodily pai, geeral health perceptios, social fuctioig, metal health, role limitatios due to emotioal problems ad vitality. 8,17 Physical compoet summary (PCS) ad metal compoet summary (MCS) scores are calculated from the domai scores; higher scores idicate better HRQoL. Age- ad geder-matched ormative values were calculated for use as a bechmark compariso ad adjusted for a mea value of The SF-36 versio 2 acute form, with a 1-week recall period, was utilized ad admiistered at Day 1 (baselie) ad 12 (or the ed of treatmet). Statistical aalyses The full aalysis set (FAS) was used for all aalyses of PROs ad icluded all patiets who were radomized i the trial ad received at least 1 dose of radomized ivestigatioal drug (tofacitiib, etaercept or placebo). For cotiuous edpoits, the chage from baselie was aalyzed usig a mixed-effect, repeated-measures model. The least-squares (LS) mea JEADV 216, 3, The Authors. Joural of the Europea Academy of Dermatology ad Veereology published by Joh Wiley & Sos Ltd o behalf of Europea Academy of Dermatology ad Veereology.

3 PROs with tofacitiib, etaercept ad placebo 1755 differeces betwee tofacitiib ad etaercept, or placebo, ad the associated % cofidece itervals were derived from this model. Biary edpoits were aalyzed usig the ormal approximatio for the differece i biomial proportios betwee tofacitiib ad etaercept, or placebo, with missig values hadled by o-respoder imputatio. No adjustmets were made for multiple testig, ad omial P values were displayed. Results Baselie characteristics ad the results of the primary aalysis, icludig PASI75 respose, PGA respose ad cliically meaigful reductio i DLQI, have bee reported previously. 13 PRO measuremets at baselie idicated a substatial burde of psoriasis, with 67.1% of patiets (733/193) reportig a PtGA score of severe ad 29.6% (324/193) reportig a score of moderate (Table 1). I compariso, physicias geerally rated patiets disease less severely ad assiged a PGA score of severe to 16.9% of patiets ad a score of moderate to 81.6% of patiets. Similar to the PtGA data, baselie DLQI scores reflected a impact of psoriasis o HRQoL: 14.9% (163/192) of patiets had a DLQI score of 21 3 (extremely large effect), 45.7% (499/192) had a DLQI score of 11 2 (a very large effect), ad a further 22.8% (249/192) had a DLQI score of 6 1 (a moderate effect). 19 The mea (stadard error [SE]) baselie ISI for treatmet groups raged from 5.2 (.3) to 5.3 (.2); a ISI score > 1 at baselie was reported by 93.6% of patiets (9/125). Mea SF-36 PCS ad MCS scores for all treatmet groups were below the ormative mea value of 5: for the PCS ad for the MCS, idicatig impairmets i physical ad metal health. Table 1 Patiet-reported outcome measuremets at baselie DLQI, mea (SE) ISI, mea (SE) PtGA, (%) Almost clear Mild Moderate Severe SF-36, mea (SE) PCS MCS Tofacitiib 5 mg BID (N = 329) (.4) (.2) 328 (.) 11 (3.4) 16 (32.3) 211 (64.3) (.5) 42. (.6) Tofacitiib 1 mg BID (N = 33) (.4) (.2) (.3) 5 (1.5) 99 (3.2) 223 (68.) (.5) 41.2 (.6) Etaercept 5 mg BIW (N = 335) (.4) (.2) 33 1 (.3) 14 (4.2) (28.5) 221 (67.) (.5) 42. (.7) Placebo (N = 17) (.7) (.3) 17 (.) 4 (3.7) 25 (23.4) 78 (72.9) (1.) 39.8 (1.2) BID, twice daily; BIW, twice weekly; DLQI, Dermatology Life Quality Idex; ISI, Itch Severity Item; MCS, metal compoet summary; PCS, physical compoet summary; PtGA, Patiet Global Assessmet of psoriasis; SE, stadard error; SF-36, Short-Form Health Survey versio 2 (acute). DLQI At 12, mea (SE) DLQI scores were 3.5 (.3) with tofacitiib 1 mg BID, 3.8 (.3) with etaercept, 5.6 (.4) with tofacitiib 5 mg BID ad 1.3 (.8) with placebo, which represeted substatial reductios from baselie i active treatmet groups; a DLQI score of 2 5 idicates oly a small effect of psoriasis o patiets lives. 19 Shifts i DLQI score from baselie to 12 are illustrated i Fig. 1. Improvemets from baselie i LS mea DLQI scores were all statistically sigificat with tofacitiib (both doses) ad etaercept vs. placebo (all P <.1). I additio, 47.3% (151/319), 43.6% (142/326) ad 3.9% (98/317) of patiets i the tofacitiib 1 mg BID, etaercept 5 mg BIW ad tofacitiib 5 mg BID groups, respectively, met the more striget criterio of o effect of psoriasis o quality of life (DLQI score of or 1) at 12: P <.1 for all comparisos vs. placebo (8/12; 7.8%) (Fig. 2). Composite PASI75 or PASI5 75 respose with DLQI 5 At 12, the proportio of patiets who achieved PASI75 or PASI5 75 with a DLQI score 5 was 73.6% (243/33) with tofacitiib 1 mg BID, compared with 73.7% (247/335), 55.3% (182/329) ad 12.2% (13/17) for etaercept 5 mg BIW, tofacitiib 5 mg BID ad placebo, respectively. Improvemets with active treatmet were sigificat vs. placebo (P <.1 for all comparisos). Itch A rapid ad substatial decrease from baselie i itch (measured by ISI) was observed i patiets receivig tofacitiib 1 ad 5 mg BID (Fig. 3). Withi 1 day of startig treatmet, both tofacitiib doses demostrated statistically sigificat reductios from baselie i LS mea (SE) ISI score: 1. (.1) for both tofacitiib 5 ad 1 mg BID (both P <.5 vs. placebo). Sigificat improvemets i itch with active treatmet (vs. placebo) were maitaied through s 2, 4, 8 ad 12 (P <.1 for etaercept at 2 ad P <.1 for all other comparisos; Fig. 3). Reductios i itch with tofacitiib 1 mg BID were sigificatly larger vs. etaercept (P <.5 for all time poits; Fig. 3). Of those patiets with a ISI score > 1 at baselie, the proportio who achieved little or o itch (ISI 1) icreased steadily i all active treatmet groups over time, with the most rapid ad substatial improvemets observed with tofacitiib 1 mg BID, followed by tofacitiib 5 mg BID ad etaercept 5 mg BIW (Fig. 4). Furthermore, a greater proportio of patiets achieved little or o itch at 2 owards with tofacitiib 1 mg BID tha with etaercept 5 mg BIW (P <.5 at all subsequet time poits). At 12, the highest proportio of patiets with little or o itch was observed i the tofacitiib 1 mg BID group (68.6% [186/271]), followed by etaercept 5 mg BIW (57.4% [16/279]), tofacitiib 5 mg BID (55.6% [153/275]) ad placebo (12.2% [12/98]). JEADV 216, 3, The Authors. Joural of the Europea Academy of Dermatology ad Veereology published by Joh Wiley & Sos Ltd o behalf of Europea Academy of Dermatology ad Veereology.

4 1756 Valezuela et al. (a) No effect (score 1) (b) Small effect (score 2 5) (c) Moderate effect (score 6 1) Proportio of patiets i the treatmet group, % Baselie 12 Proportio of patiets i the treatmet group, % Baselie 12 Proportio of patiets i the treatmet group, % Baselie 12 (d) Very large effect (score 11 2) (e) Extremely large effect (score 21 3) Proportio of patiets i the treatmet group, % Baselie 12 Proportio of patiets i the treatmet group, % Baselie 12 Tofacitiib 5 mg BID Tofacitiib 1 mg BID Etaercept 5 mg BIW Placebo Figure 1 Proportio of patiets i DLQI categories at baselie ad 12, categorized accordig to the effect of the disease o patiets lives as per previously described classificatio 19 (FAS, observed cases). BID, twice daily; BIW, twice weekly; DLQI, Dermatology Life Quality Idex; FAS, full aalysis set. Proportio achievig DLQI 1 (SE) Tofacitiib 5 mg BID, N = 317 Tofacitiib 1 mg BID, N = 319 Etaercept 5 mg BIW, N = 326 Placebo, N = Figure 2 Proportio of patiets at baselie, 4 ad 12 with a DLQI score of 1, idicatig o effect of psoriasis o quality of life (FAS, NRI). P <.5, P <.1 vs. placebo. BID, twice daily; BIW, twice weekly; FAS, full aalysis set; DLQI, Dermatology Life Quality Idex; NRI, o-respoder imputatio; SE, stadard error. PtGA The PtGA respose rate i the tofacitiib 1 mg BID group was sigificatly greater vs. placebo at 2 (P <.5), idicatig a rapid oset of effect (Fig. 5). From 4 owards, the respose rate for all active treatmet groups was sigificatly greater tha with placebo (P <.1 for all comparisos). I additio, there was a higher proportio of respoders i the tofacitiib 1 mg BID group vs. etaercept 5 mg BIW group at ad 8 (P <.5 for both comparisos). By 12, the respose rates were similar i the tofacitiib 1 mg BID ad etaercept groups (51.8% ad 49.%, respectively) compared with 3.4% for tofacitiib 5 mg BID ad.9% for placebo. SF-36 PCS ad MCS scores Improvemets i PCS ad MCS scores were observed i all groups at 12 (Table 2). I active treatmet groups, mea PCS exceeded the mea age- ad geder-matched ormative value, whereas i the placebo group, they remaied below this value. Similarly, MCS scores i active treatmet groups approached ormative values, while correspodig values i the placebo group remaied low (data ot show). A highly sigificat improvemet from baselie i health status was observed for all eight domais ad scores of the SF-36 i all active treatmet groups at 12, compared with the placebo group (P <.1 for geeral health ad health trasitio score ; P <.1 for all other domais ad scores; Table 2). Discussio From a patiet perspective, the importace of PROs i psoriasis maagemet should ot be uderstated. Improvemets i PROs are ot oly associated with better HRQoL for the patiet 2 but also have a positive secodary impact o the lives of patiets relatives ad parters. 21 Nevertheless, studies o patiet perspectives suggest a discoect with physicias regardig the JEADV 216, 3, The Authors. Joural of the Europea Academy of Dermatology ad Veereology published by Joh Wiley & Sos Ltd o behalf of Europea Academy of Dermatology ad Veereology.

5 PROs with tofacitiib, etaercept ad placebo 1757 (a) (b) LS mea chage from baselie (SE) Day Tofacitiib 5 mg BID Tofacitiib 1 mg BID Etaercept 5 mg BIW Placebo Figure 3 LS mea chage i itch (measured by ISI) from (a) baselie to Day 15 (patiet diary etries) ad (b) from 2 to 12 (cliic assessmets) (FAS, observed cases). The last patiet diary etry was scheduled for the eveig before the 2 visit. However, ot all patiets completed the diary for the etirety of the iteded period. Also, the widow for the 2 visit was Day 15 3 days; hece, the 2 visit did ot ecessarily take place o Day 15 for all participats. The 2 assessmet was made for all patiets at the cliic, ad these differeces accout for the apparet differece i ISI values betwee Day 15 ad 2. Days 1 15: tofacitiib 5 mg BID N = 291, tofacitiib 1 mg BID N = 296, etaercept N = 29, placebo N = : tofacitiib 5 mg BID N =, tofacitiib 1 mg BID N = 36, etaercept N =, placebo N = 17. P <.5, P <.1, P <.1 vs. placebo. BID, twice daily; BIW, twice weekly; FAS, full aalysis set; ISI, itch severity item; LS, least squares; SE, stadard error. Proportio with ISI of or 1 (SE) 1 Tofacitiib 5 mg BID, N = 275 Tofacitiib 1 mg BID, N = Etaercept 5 mg BIW, N = Placebo, N = Figure 4 Proportio of patiets with a baselie ISI score > 1 who reported little or o itch (score of or 1) at a subsequet visit (FAS, NRI). P <.5, P <.1 vs. placebo. BID, twice daily; BIW, twice weekly; FAS, full aalysis set; ISI, itch severity item; NRI, o-respoder imputatio; SE, stadard error. Proportio with PtGA of or 1 (SE) 1 Tofacitiib 5 mg BID, N = 329 Tofacitiib 1 mg BID, N = 33 9 Etaercept 5 mg BIW, N = Placebo, N = Figure 5 Mea (SE) proportio of patiets with a PtGA score of clear or 1 almost clear (FAS, NRI). P <.5, P <.1 vs. placebo. BID, twice daily; BIW, twice weekly; FAS, full aalysis set; NRI, o-respoder imputatio; PtGA, Patiet Global Assessmet; SE, stadard error. extet of disease that patiets experiece. 22,23 Here, we foud that patiets rate their disease more severely tha physicias do, highlightig the eed for greater physicia patiet commuicatio i order to fully uderstad the patiet experiece. The Phase 3 OPT Compare Study i patiets with moderate to severe psoriasis was the first direct head-to-head compariso of the oral small-molecule tofacitiib with the biologic aget etaercept (the stadard-of-care treatmet i this settig). I this aalysis, sigificat improvemets i patiet-reported measures of disease severity ad improvemets across multiple domais of HRQoL were observed with tofacitiib by 12 ad ofte cosiderably earlier. Compared with etaercept, the magitude of improvemets i PROs with tofacitiib was comparable i patiets dosed with 5 mg BID ad greater i patiets dosed with 1 mg BID fidigs that complemet the observed primary efficacy outcomes. 13 It should be oted that the dose of JEADV 216, 3, The Authors. Joural of the Europea Academy of Dermatology ad Veereology published by Joh Wiley & Sos Ltd o behalf of Europea Academy of Dermatology ad Veereology.

6 1758 Valezuela et al. Table 2 LS mea chages from baselie i SF-36 PCS, MCS ad idividual domai scores, at 12 (FAS, observed cases) SF-36 domai score, mea chage (SE) Tofacitiib 5 mg BID Tofacitiib 1 mg BID Etaercept 5 mg BIW Placebo PCS MCS Physical fuctioig Role physical Bodily pai Geeral health Vitality Social fuctioig Role emotioal Metal health Health trasitio score (.4) (.4) (.4) 93.5 (.7) (.5) (.4) (.5) 4.1 (.4) (.5) 3.7 (.4) 93.7 (.9).3 (.7) (.4) (.5) 6.7 (.4) 9.3 (.5) 5.9 (.4) 8. (.5).9 (.7) 1.2 (.9) 2.7 (.4) (.4) (.4) 5.7 (.5) 4.5 (.4) 4.6 (.5) -.2 (.7).4 (.8) (.5) (.5) (.5) 9. (.5) 7.3 (.5) 7.5 (.5) 5.8 (.5).5 (.9) 1.2 (.9) 36.5 (<.1) 7.1 (.5) 33.6 (<.1) 5.9 (.5) 36.6 (<.1).5 (.9).2 (.1) P <.1, P <.1 vs. placebo. BID, twice daily; BIW, twice weekly; FAS, full aalysis set; LS, least squares; MCS, metal compoet score; PCS, physical compoet score; SE, stadard error; SF-36, Short-Form Health Survey versio 2 (acute). etaercept evaluated i the trial (5 mg BIW) is the highest dose approved by the US Food ad Drug Admiistratio ad Europea Medicies Agecy for the treatmet of psoriasis 24 ad may be give for up to 12 weeks. 25 The reliability ad validity of the DLQI i a psoriasis populatio has bee well documeted. 26 I additio, the miimally importat differece (MID) i DLQI has bee estimated as a 5-poit chage from baselie, 27 which was achieved by 66.3% (tofacitiib 5 mg BID), 78.2% (tofacitiib 1 mg BID) ad 74.7% (etaercept) of patiets i this trial. 13 A recet reassessmet of the MID i DLQI led to the recommedatio that the MID should be lowered to 4, 28 which would mea that a eve greater proportio of patiets i this trial achieved a cliically sigificat improvemet i DLQI. I additio to PASI75 respoders, we also examied a composite edpoit defied by Europea cosesus guidelies for the treatmet goals of moderate to severe psoriasis. 15 These guidelies recommed that i patiets who achieve a improvemet i PASI score 5% but < 75%, treatmet should be cotiued if DLQI is 5 or modified if the DLQI score is > 5 at the ed of iductio therapy or durig maiteace therapy. I our study, more tha 7% of patiets receivig tofacitiib 1 mg BID or etaercept 5 mg BIW, ad more tha 5% of patiets receivig tofacitiib 5 mg BID, achieved this composite edpoit of PASI75 or PASI5 75 with DLQI 5. Itch is cosidered by patiets to be the most bothersome symptom of psoriasis 29 ad is more likely to cause absece from work ad reduced work productivity tha psoriasisrelated pai or scalig. 3 I the preset study, a rapid oset of treatmet effect o itch was observed as early as withi 1 day of startig treatmet; improvemets i itch were see earlier with tofacitiib 1 mg BID tha with etaercept. Give the cosiderable burde that itch represets for patiets with psoriasis, ad that itch relief ca ofte be slow eve with treatmet, this fidig idicates that tofacitiib may be associated with more effective ad quicker relief from itch compared with etaercept, which would be of great importace to patiets. Potetial limitatios of this study iclude its relatively short duratio of 12 weeks. Log-term studies of tofacitiib i moderate to severe psoriasis are ogoig; 1-year data show sustaied improvemets i DLQI ad itch (measured by ISI) with tofacitiib. 31 I coclusio, this study demostrates that tofacitiib is effective across a rage of sigs ad symptoms of moderate to severe plaque psoriasis, icludig PROs ad HRQoL. I geeral, improvemets i PROs ad HRQoL observed with tofacitiib 1 mg BID were comparable with etaercept. However, improvemets i itch were greater ad more rapid with tofacitiib 1 mg BID vs. etaercept, suggestig that tofacitiib may JEADV 216, 3, The Authors. Joural of the Europea Academy of Dermatology ad Veereology published by Joh Wiley & Sos Ltd o behalf of Europea Academy of Dermatology ad Veereology.

7 PROs with tofacitiib, etaercept ad placebo 1759 represet a potetial future treatmet optio for patiets with moderate to severe plaque psoriasis. Ackowledgmets The authors would like to thak the patiets who were ivolved i this study, as well as the A39218 ivestigators ad OPT Compare Study teams. This work was supported by Pfizer Ic. Medical writig support was provided by Claire Cridlad at Complete Medical Commuicatios ad was fuded by Pfizer Ic. Refereces 1 Lagley RG, Krueger GG, Griffiths CE. Psoriasis: epidemiology, cliical features, ad quality of life. A Rheum Dis 25; 64(Suppl 2): ii18 ii23. 2 Gordo KB, Lagley RG, Leoardi C et al. Cliical respose to adalimumab treatmet i patiets with moderate to severe psoriasis: doubleblid, radomized cotrolled trial ad ope-label extesio study. JAm Acad Dermatol 26; 55: Reich K, Nestle FO, Papp K et al. Ifliximab iductio ad maiteace therapy for moderate-to-severe psoriasis: a phase III, multicetre, double-blid trial. 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Joural of the Europea Academy of Dermatology ad Veereology published by Joh Wiley & Sos Ltd o behalf of Europea Academy of Dermatology ad Veereology.