Ixekizumab, an interleukin-17A specific monoclonal antibody, for the treatment of biologic-naive patients with active psoriatic arthritis: results from the 24-week randomised, double-blind, placebo-controlled and active (adalimumab)-controlled period of the phase III trial SPIRIT-P1 Effect of certolizumab pegol on signs and symptoms in patients with psoriatic arthritis: 24-week results of a Phase 3 double-blind randomised placebo-controlled study (RAPID-PsA) Secukinumab Inhibition of Interleukin-17A in Patients with Psoriatic Arthritis. Secukinumab Versus Adalimumab for Psoriatic Arthritis: Comparative Effectiveness up to 48 Weeks Using a Matching-Adjusted Indirect Comparison Infliximab improves signs and symptoms of psoriatic arthritis: results of the IMPACT 2 trial. Treatment of psoriatic arthritis in a phase 3 randomised, placebo-controlled trial with apremilast, an oral phosphodiesterase 4 inhibitor Etanercept in the treatment of psoriatic arthritis and psoriasis: a randomised trial Safety and efficacy of adalimumab in treatment of patients with psoriatic arthritis who had failed disease modifying antirheumatic drug therapy. Adalimumab for the treatment of patients with moderately to severely active psoriatic arthritis: results of a double-blind, randomized, placebo-controlled trial. Comparison of two etanercept regimens for treatment of psoriasis and psoriatic arthritis: PRESTA randomised double blind multicentre trial Secukinumab Improves Physical Function in Subjects With Plaque Psoriasis and Psoriatic Arthritis: Results from Two Randomized, Phase 3 Trials. Comparison of ustekinumab and etanercept for moderate-to-severe psoriasis. Efficacy and safety of the anti-IL-12/23 p40 monoclonal antibody, ustekinumab, in patients with active psoriatic arthritis despite conventional non-biological and biological anti-tumour necrosis factor therapy: 6-month and 1-year results of the phase 3, multicentre, double-blind, placebo-controlled, Oral apremilast in the treatment of active psoriatic arthritis: results of a multicenter, randomized, double-blind, placebo-controlled study. Efficacy and safety of ustekinumab in patients with active psoriatic arthritis: 1 year results of the phase 3, multicentre, double-blind, placebo-controlled PSUMMIT 1 trial Secukinumab is superior to ustekinumab in clearing skin of subjects with moderate‐to‐severe plaque psoriasis up to 1 year: Results from the CLEAR study Sustained benefits of infliximab therapy for dermatologic and articular manifestations of psoriatic arthritis: results from the infliximab multinational psoriatic arthritis controlled trial (IMPACT). Etanercept treatment of psoriatic arthritis: safety, efficacy, and effect on disease progression. Golimumab, a new human tumor necrosis factor alpha antibody, administered every four weeks as a subcutaneous injection in psoriatic arthritis: Twenty-four-week efficacy and safety results of a randomized, placebo-controlled study. A Phase III, Randomized, Controlled Trial of Apremilast in Patients with Psoriatic Arthritis: Results of the PALACE 2 Trial Secukinumab, a human anti-interleukin-17A monoclonal antibody, in patients with psoriatic arthritis (FUTURE 2): a randomised, double-blind, placebo-controlled, phase 3 trial
Objective To assess the safety and efficacy of ixekizumab , a monoclonal antibody that inhibits interleukin-17A , in a double-blind phase III trial enrolling patients with active psoriatic arthritis ( PsA ) . Methods Patients naive to biologic therapy with active PsA were r and omised to subcutaneous injections of placebo ( N=106 ) , adalimumab 40 mg once every 2 weeks ( active reference ; N=101 ) , ixekizumab 80 mg once every 2 weeks ( IXEQ2W ) ( N=103 ) , or ixekizumab 80 mg once every 4 weeks ( IXEQ4W ) ( N=107 ) . Both ixekizumab regimens included a 160-mg starting dose . The primary objective was to assess the superiority of IXEQ2W or IXEQ4W versus placebo as measured by the proportion of patients achieving an American College of Rheumatology 20 ( ACR20 ) response at week 24 . Results Significantly more patients treated with ixekizumab achieved an ACR20 response with IXEQ2W ( 62.1 % ) or IXEQ4W ( 57.9 % ) than placebo ( 30.2 % ) ( p≤0.001 ; non-responder imputation method ) . Disease activity and functional disability were significantly improved with both ixekizumab doses versus placebo at weeks 12 and 24 , and there was significantly less progression of structural damage at week 24 ( p≤0.01 ) . Clearance of plaque psoriasis was greater with ixekizumab than placebo ( p≤0.001 ) . Efficacy results with adalimumab , the active reference arm , showed significant improvements versus placebo . Treatment-emergent adverse events were more frequent with ixekizumab ( 65.7–66.4 % ) and adalimumab ( 64.4 % ) than placebo ( 47.2 % ) ( p<0.05 ) . Conclusions In biologic-naive patients with active PsA  , ixekizumab treatment result ed in improvements in disease activity and physical function , as well as in the inhibition of structural damage progression . Overall , adverse events were more frequent in all active groups compared with placebo . Trial registration number NCT01695239 ; EudraCT2011 - 002326 - 49 ; Results Objectives To evaluate the efficacy and safety of certolizumab pegol ( CZP ) after 24 weeks in RAPID-PsA ( NCT01087788 ) , an ongoing Phase 3 trial in patients with psoriatic arthritis ( PsA ) . Methods Patients were r and omised 1:1:1 to placebo  , 200 mg CZP every 2 weeks ( Q2W ) or 400 mg CZP every 4 weeks ( Q4W ) . Patients could have had exposure to one previous tumour necrosis factor ( TNF ) inhibitor therapy . Primary endpoints were American College of Rheumatology 20 % ( ACR20 ) response at week 12 and modified Total Sharp Score change from baseline at week 24 . Secondary endpoints included ; Psoriatic Arthritis Response Criteria ( PsARC ) score , Health Assessment Question naire Disability Index ( HAQ-DI ) , Psoriasis Area and Severity Index , Leeds Enthesitis Index , Leeds Dactylitis Index , and Modified Nail Psoriasis Severity Index . Results Of 409 patients r and omised , 368 completed 24 weeks of treatment .  ACR20 response was significantly greater in CZP 200 mg Q2W and 400 mg Q4W-treated patients than placebo ( 58.0 % and 51.9 % vs 24.3 % ( p<0.001 ) ) at week 12 , with improvements observed by week 1 . There was a statistically significant improvement in physical function from baseline , measured by HAQ-DI in CZP patients compared with placebo ( −0.50 vs −0.19 , p<0.001 ) and more patients treated with CZP 200 mg Q2W and CZP 400 mg achieved an improvement in PsARC at week 24 than placebo ( 78.3 % and 77.0 % vs 33.1 % ( p<0.001 ) ) . Sustained improvements were observed in psoriatic skin involvement , enthesitis , dactylitis and nail disease . Higher ACR20 response with CZP was independent of prior TNF inhibitor exposure . No new safety signals were observed . Conclusions Rapid improvements in the signs and symptoms of PsA , including joints , skin , enthesitis , dactylitis and nail disease were observed across both CZP dosing regimens BACKGROUND In a phase 2 study , the inhibition of the interleukin-17A receptor improved signs and symptoms of psoriatic arthritis . We sought to evaluate the efficacy and safety of secukinumab , an anti-interleukin-17A monoclonal antibody , in such patients . METHODS In this double-blind , phase 3 study , 606 patients with psoriatic arthritis were r and omly assigned in a 1:1:1 ratio to receive intravenous secukinumab ( at a dose of 10 mg per kilogram ) at weeks 0 , 2 , and 4 , followed by subcutaneous secukinumab at a dose of either 150 mg or 75 mg every 4 weeks , or placebo . Patients in the placebo group were switched to subcutaneous secukinumab at a dose of 150 mg or 75 mg at week 16 or 24 , depending on clinical response . The primary end point was the proportion of patients with an American College of Rheumatology 20 ( ACR20 ) response at week 24 , defined as a 20 % improvement from baseline in the number of tender and swollen joints and at least three other important domains . RESULTS ACR20 response rates at week 24 were significantly higher in the group receiving secukinumab at doses of 150 mg ( 50.0 % ) and 75 mg ( 50.5 % ) than in those receiving placebo ( 17.3 % ) ( P<0.001 for both comparisons with placebo ) . Secondary end points , including the ACR50 response and joint structural damage , were significantly better in the secukinumab groups than in the placebo group . Improvements were sustained through 52 weeks . Infections , including c and ida , were more common in the secukinumab groups . Throughout the study ( mean secukinumab exposure , 438.5 days ; mean placebo exposure , 128.5 days ) , four patients in the secukinumab groups had a stroke ( 0.6 per 100 patient-years ; 95 % confidence interval [ CI ] , 0.2 to 1.5 ) , and two had a myocardial infa rct ion ( 0.3 per 100 patient-years ; 95 % CI , 0.0 to 1.0 ) , as compared with no patients in the placebo group . CONCLUSIONS Secukinumab was more effective than placebo in patients with psoriatic arthritis , which vali date s interleukin-17A as a therapeutic target . Infections were more common in the secukinumab groups than in the placebo group . The study was neither large enough nor long enough to evaluate uncommon serious adverse events or the risks associated with long-term use . ( Funded by Novartis Pharma ; Clinical Trials.gov number , NCT01392326 . ) Introduction Secukinumab and adalimumab are approved for adults with active psoriatic arthritis ( PsA ) . In the absence of direct r and omized controlled trial ( RCT ) data , matching-adjusted indirect comparison can estimate the comparative effectiveness in anti-tumor necrosis factor (TNF)-naïve population s. Methods Individual patient data from the FUTURE 2 RCT ( secukinumab vs. placebo ; N = 299 ) were adjusted to match baseline characteristics of the ADEPT RCT ( adalimumab vs. placebo ; N = 313 ) . Logistic regression determined adjustment weights for age , body weight , sex , race , methotrexate use , psoriasis affecting ≥ 3 % of body surface area , Psoriasis Area and Severity Index score , Health Assessment Question naire Disability Index score , presence of dactylitis and enthesitis , and previous anti-TNF therapy . Recalculated secukinumab outcomes were compared with adalimumab outcomes at weeks 12 ( placebo-adjusted ) , 16 , 24 , and 48 ( nonplacebo-adjusted ) . Results After matching , the effective sample size for FUTURE 2 was 101 . Week 12 American College of Rheumatology ( ACR ) response rates were not significantly different between secukinumab and adalimumab . Week 16 ACR 20 and 50 response rates were higher for secukinumab 150 mg than for adalimumab ( P = 0.017 , P = 0.033 ) , as was ACR 50 for secukinumab 300 mg ( P = 0.030 ) . Week 24 ACR 20 and 50 were higher for secukinumab 150 mg than for adalimumab ( P = 0.001 , P = 0.019 ) , as was ACR 20 for secukinumab 300 mg ( P = 0.048 ) . Week 48 ACR 20 was higher for secukinumab 150 and 300 mg than for adalimumab ( P = 0.002 , P = 0.027 ) , as was ACR 50 for secukinumab 300 mg ( P = 0.032 ) . Conclusions In our analysis , patients with PsA receiving secukinumab  were more likely to achieve higher ACR responses through 1 year ( weeks 16–48 ) than those treated with adalimumab . Although informative , these observations rely on a subgroup of patients from FUTURE 2 and thus should be considered interim until the ongoing head-to-head RCT EXCEED can vali date these findings . Funding Novartis Pharma AG OBJECTIVES To evaluate further in a phase III , double blind trial the efficacy of infliximab in patients with active psoriatic arthritis ( PsA ) , as observed in the smaller IMPACT trial . METHODS 200 patients with active PsA unresponsive to previous treatment were r and omised to infusions of infliximab 5 mg/kg or placebo at weeks 0 , 2 , 6 , 14 , and 22 . Patients with inadequate response entered early escape at week 16 . The primary measure of clinical response was ACR20 . Other measures included Psoriatic Arthritis Response Criteria ( PsARC ) , Psoriasis Area and Severity Index ( PASI ) , and dactylitis and enthesopathy assessment s. RESULTS At week 14 , 58 % of patients receiving infliximab and 11 % of those receiving placebo achieved an ACR20 response and 77 % of infliximab patients and 27 % of placebo patients achieved PsARC ( both p<0.001 ) . Among the 85 % of patients with at least 3 % body surface area psoriasis involvement at baseline , 53/83 ( 64 % ) patients receiving infliximab had at least 75 % improvement in PASI compared with 2/87 ( 2 % ) patients receiving placebo at week 14 ( p<0.001 ) . These therapeutic effects were maintained through the last evaluation ( week 24 ) . Fewer infliximab patients than placebo patients had dactylitis at week 14 ( 18 % v 30 % ; p = 0.025 ) and week 24 ( 12 % v 34 % ; p<0.001 ) . Fewer infliximab patients ( 22 % ) than placebo patients ( 34 % ) had active enthesopathy at week 14 ( p = 0.016 ) ; corresponding figures at week 24 were 20 % and 37 % ( p = 0.002 ) . Infliximab was generally well tolerated , with a similar incidence of adverse events in each group . CONCLUSIONS Infliximab 5 mg/kg through 24 weeks significantly improved active PsA , including dactylitis and enthesopathy , and associated psoriasis Objectives Apremilast , an oral phosphodiesterase 4 inhibitor , regulates inflammatory mediators . Psoriatic Arthritis Long-term Assessment of Clinical Efficacy 1 ( PALACE 1 ) compared apremilast with placebo in patients with active psoriatic arthritis despite prior traditional disease-modifying antirheumatic drug ( DMARD ) and /or biologic therapy . Methods In the 24-week , placebo-controlled phase of PALACE 1 , patients ( N=504 ) were r and omised ( 1:1:1 ) to placebo , apremilast 20 mg twice a day ( BID ) or apremilast 30 mg BID . At week 16 , patients without ≥20 % reduction in swollen and tender joint counts  were required to be re-r and omised equally to either apremilast dose if initially r and omised to placebo or remained on their initial apremilast dose . Patients on background concurrent DMARDs continued stable doses ( methotrexate , leflunomide and /or sulfasalazine ) . Primary outcome was the proportion of patients achieving 20 % improvement in modified American College of Rheumatology response criteria ( ACR20 ) at week 16 . Results At week 16 , significantly more apremilast 20 mg BID ( 31 % ) and 30 mg BID ( 40 % ) patients achieved ACR20  versus placebo ( 19 % ) ( p<0.001 ) . Significant improvements in key secondary measures ( physical function , psoriasis ) were evident with both apremilast doses versus placebo . Across outcome measures , the 30-mg group generally had higher and more consistent response rates , although statistical comparison was not conducted . The most common adverse events were gastrointestinal and generally occurred early , were self-limiting and infrequently led to discontinuation . No imbalance in major adverse cardiac events , serious or opportunistic infections , malignancies or laboratory abnormalities was observed . Conclusions Apremilast was effective in the treatment of psoriatic arthritis , improving signs and symptoms and physical function . Apremilast demonstrated an acceptable safety profile and was generally well tolerated . Clinical trial registration number NCT01172938 BACKGROUND Etanercept , a tumour-necrosis-factor inhibitor , has shown efficacy in the treatment of rheumatoid arthritis . Psoriatic arthritis and psoriasis are disease states in which tumour necrosis factor , a proinflammatory cytokine , is present in increased concentrations in joints and in the skin . Therefore , psoriatic arthritis and psoriasis may be appropriate therapeutic targets for etanercept . METHODS This r and omised , double-blind , placebo-controlled , 12 week study assessed the efficacy and safety of etanercept ( 25 mg twice-weekly subcutaneous injections ) or placebo in 60 patients with psoriatic arthritis and psoriasis . Psoriatic arthritis endpoints included the proportion of patients who met the Psoriatic Arthritis Response Criteria ( PsARC ) and who met the American College of Rheumatology preliminary criteria for improvement ( ACR20 ) . Psoriasis endpoints included improvement in the psoriasis area and severity index ( PASI ) and improvement in prospect ively-identified individual target lesions . FINDINGS In this 12 week study , 26 ( 87 % ) of etanercept-treated patients met the PsARC , compared with seven ( 23 % ) of placebo-controlled patients . The ARC20 was achieved by 22 ( 73 % ) of etanercept-treated patients compared with four ( 13 % ) of placebo-treated patients . Of the 19 patients in each treatment group who could be assessed for psoriasis ( > or = 3 % body surface area ) , five ( 26 % ) of etanercept-treated patients achieved a 75 % improvement in the PASI , compared with none of the placebo-treated patients ( p=0.015 ) . The median PASI improvement was 46 % in etanercept-treated patients versus 9 % in placebo-treated patients ; similarly , median target lesion improvements were 50 % and 0 , respectively . Etanercept was well tolerated . INTERPRETATION Etanercept offers patients with psoriatic arthritis and psoriasis a new therapeutic option for control of their disease OBJECTIVE To demonstrate the safety and efficacy of adalimumab for the treatment of active psoriatic arthritis ( PsA ) in patients with an inadequate response to disease modifying antirheumatic drugs ( DMARD ) . METHODS In a placebo controlled , double-blind , r and omized , multicenter study , patients were treated for 12 weeks with subcutaneous injections of adalimumab 40 mg every other week ( eow ) or placebo , followed by a period of open-label treatment with adalimumab 40 mg eow . The primary efficacy endpoint was the percentage of patients who met the American College of Rheumatology ( ACR20 ) core criteria at Week 12 . Secondary efficacy measures included the modified Psoriatic Arthritis Response Criteria ( PsARC ) and assessment s of disability , psoriatic lesions , and quality of life . For missing data , nonresponder imputation was used for ACR and PsARC scores and last observation carried forward for other measures . RESULTS A total of 100 patients received study drug ( 51  adalimumab  , 49 placebo )  . At Week 12 , an ACR20 response was achieved by 39 % of adalimumab patients versus 16 % of placebo patients ( p = 0.012 ) , and a PsARC response was achieved by 51 % with adalimumab versus 24 % with placebo ( p = 0.007 ) . At Week 12 , measures of skin lesions and disability were statistically significantly improved with adalimumab . After Week 12 , open-label adalimumab provided continued improvement for adalimumab patients and initiated rapid improvement for placebo patients , with ACR20 response rates of 65 % and 57 % , respectively , observed at Week 24 . Serious adverse events had similar frequencies during therapy with placebo ( 4.1 % ) , blinded adalimumab ( 2.0 % ) , and open-label adalimumab ( 3.1 % ) . No serious infections occurred during adalimumab therapy . CONCLUSION In this study of patients who had active PsA and a previous , inadequate response to DMARD therapy , adalimumab was well tolerated and significantly reduced the signs , symptoms , and disability of PsA during 12 weeks of blinded and 12 weeks of open-label therapy . Adalimumab also improved psoriasis in these patients OBJECTIVE Adalimumab , a fully human , anti-tumor necrosis factor monoclonal antibody , was evaluated for its safety and efficacy compared with placebo in the treatment of active psoriatic arthritis ( PsA ) . METHODS Patients with moderately to severely active PsA and a history of inadequate response to nonsteroidal antiinflammatory drugs were r and omized to receive 40 mg adalimumab or placebo subcutaneously every other week for 24 weeks . Study visits were at baseline , weeks 2 and 4 , and every 4 weeks thereafter . The primary efficacy end points were the American College of Rheumatology 20 % improvement ( ACR20 ) response at week 12 and the change in the modified total Sharp score of structural damage at week 24 . Secondary end points were measures of joint disease , disability , and quality of life in all patients , as well as the severity of skin disease in those patients with psoriasis involving at least 3 % of body surface area . RESULTS At week 12 , 58 % of the adalimumab-treated patients ( 87 of 151 ) achieved an ACR20 response , compared with 14 % of the placebo-treated patients ( 23 of 162 ) ( P < 0.001 ) . At week 24 , similar ACR20 response rates were maintained and the mean change in the modified total Sharp score was -0.2 in patients receiving adalimumab and 1.0 in those receiving placebo ( P < 0.001 ) . Among the 69 adalimumab-treated patients evaluated with the Psoriasis Area and Severity Index ( PASI ) , 59 % achieved a 75 % PASI improvement response at 24 weeks , compared with 1 % of the 69 placebo-treated patients evaluated ( P < 0.001 ) . Disability and quality of life measures were also significantly improved with adalimumab treatment compared with placebo . Adalimumab was generally safe and well-tolerated . CONCLUSION Adalimumab significantly improved joint and skin manifestations , inhibited structural changes on radiographs , lessened disability due to joint damage , and improved quality of life in patients with moderately to severely active Objectives To compare the efficacy over 12 weeks of two different etanercept regimens in treating the skin manifestations of psoriasis in patients who also have psoriatic arthritis and to evaluate efficacy and safety over an additional 12 weeks of open label etanercept treatment . Design R and omised double blind multicentre outpatient study . Setting 98 outpatient facilities in Europe , Latin America , and the Asia Pacific region . Participants 752 patients with both psoriasis ( evaluated by dermatologists ) and psoriatic arthritis ( evaluated by rheumatologists ) . Interventions During the blinded portion of the study , participants were r and omised to receive etanercept 50 mg twice weekly ( n=379 ) or 50 mg once weekly ( n=373 ) for 12 weeks by subcutaneous injection . All participants then received open label etanercept 50 mg once weekly for 12 additional weeks , while remaining blinded to the regimen . Main outcome measures The primary efficacy end point was the proportion of participants achieving “ clear ” or “ almost clear ” on the physician ’s global assessment of psoriasis at week 12 . Secondary efficacy analyses included psoriasis area and severity index , American College of Rheumatology responses , psoriatic arthritis response criteria , and improvement in joint and tendon disease manifestations . Results At week 12 , 46 % ( 176/379 ) of participants receiving etanercept 50 mg twice weekly achieved a physician ’s global assessment of psoriasis of “ clear ” or “ almost clear ” compared with 32 % ( 119/373 ) in the group treated with 50 mg once weekly ( P<0.001 ) . In contrast , an equally high percentage of participants in both groups achieved psoriatic arthritis response criteria ( 77 % ( 284/371 ) in the twice weekly/once weekly group versus 76 % ( 282/371 ) in the once weekly/once weekly group ) . Participants treated with 50 mg twice weekly/once weekly had greater mean reductions from baseline in the psoriasis area and severity index at week 12 compared with those who received 50 mg once weekly/once weekly ( 71 % v 62 % , P<0.001 ) , with less difference at week 24 ( 78 % v 74 % , P<0.110 ) . Joint and tendon disease manifestations improved from baseline in both groups to a similar extent . No new safety signals were seen in either etanercept treatment group , and no significant difference in the safety profiles was observed . Conclusions In participants with active psoriasis and psoriatic arthritis , initial treatment of the psoriasis with etanercept 50 mg twice weekly may allow for more rapid clearance of skin lesions than with 50 mg once weekly . A regimen of 50 mg once weekly seems to be appropriate for treatment of joint and tendon rheumatic symptoms . The choice of regimen should be determined by the clinical needs of the individual patient . Trial registration Clinical trials NCT00245960 BACKGROUND Interleukin (IL)-17A is a key cytokine in the pathogenesis of psoriatic disease of the skin and joints . In phase 3 trials , secukinumab , a fully human anti-IL-17A monoclonal antibody , demonstrated robust efficacy in psoriasis , with rapid onset , high response rates , and durable response . OBJECTIVE To evaluate the efficacy of secukinumab in subjects with psoriasis and concomitant psoriatic arthritis ( PsA ) with respect to psoriasis symptoms and physical function , we conducted pre-specified subanalyses of the phase 3 FIXTURE and ERASURE trials . METHODS The 52-week FIXTURE and ERASURE trials r and omized subjects with moderate-to-severe plaque psoriasis to subcutaneous secukinumab 300 or 150 mg ( Baseline , weeks 1 , 2 , 3 , every 4 weeks from week 4 until week 48 ) , etanercept 50 mg ( twice weekly through week 12 , once weekly thereafter through week 51 ; FIXTURE only ) , or placebo . In this analysis , changes in Health Assessment Question naire-Disability Index ( HAQ-DI ) and PASI 75 responses were assessed in sub population s with concomitant PsA ( n=196 , FIXTURE ; n=171 , ERASURE ) . RESULTS Physical functioning ( mean change from Baseline in HAQ-DI ) was greater with secukinumab 300 mg vs. placebo at week 12 in both trials ( FIXTURE , -0.41 vs. 0.02/P=0.0001 ; ERASURE , -0.35 vs. -0.08/P=0.0003 ) ; corresponding values were -0.29 for etanercept and -0.19 for secukinumab 150 mg in FIXTURE and -0.18 for secukinumab 150 mg in ERASURE . Greater responses were seen in subjects with greater Baseline disability ( HAQ-DI ≥05 ) . Week 12 PASI 75 responses were higher with secukinumab 300 mg/150 mg vs. placebo in FIXTURE ( 72%/59 % vs. 2 % ) and ERASURE ( 68%/70 % vs. 4 % ; all P<0.0001 ) and with secukinumab 300 mg vs. etanercept ( 72 % vs 39 % ; P=0.0084 ) . CONCLUSION Secukinumab 300 mg produced significant improvement in  psoriasis and physical functioning in subjects with concomitant PsA. Clinical Trials.gov numbers : NCT01358578 ( FIXTURE ) ; NCT01365455 ( ERASURE BACKGROUND Biologic agents offer a range of new therapeutic options for patients with psoriasis ; however , the relative benefit-risk profiles of such therapies are not well known . We compared two biologic agents , ustekinumab ( an interleukin-12 and interleukin-23 blocker ) and etanercept ( an inhibitor of tumor necrosis factor alpha ) , for the treatment of psoriasis . METHODS We r and omly assigned 903 patients with moderate-to-severe psoriasis to receive subcutaneous injections of either 45 or 90 mg of ustekinumab ( at weeks 0 and 4 ) or high-dose etanercept ( 50 mg twice weekly for 12 weeks ) . The primary end point was the proportion of patients with at least 75 % improvement in the psoriasis area- and -severity index ( PASI ) at week 12 ; a secondary end point was the proportion with cleared or minimal disease on the basis of the physician 's global assessment . Assessors were unaware of the treatment assignments . The efficacy and safety of a crossover from etanercept to ustekinumab were evaluated after week 12 . RESULTS There was at least 75 % improvement in the PASI at week 12 in 67.5 % of patients who received 45 mg of ustekinumab and 73.8 % of patients who received 90 mg , as compared with 56.8 % of those who received etanercept ( P=0.01 and P<0.001 , respectively ) . Similarly , 65.1 % of patients who received 45 mg of ustekinumab and 70.6 % of patients who received 90 mg of ustekinumab had cleared or minimal disease according to the physician 's global assessment , as compared with 49.0 % of those who received etanercept ( P<0.001 for both comparisons ) . Among patients who did not have a response to etanercept , 48.9 % had at least 75 % improvement in the PASI within 12 weeks after crossover to ustekinumab . One or more adverse events occurred through week 12 in 66.0 % of patients who received 45 mg of ustekinumab and 69.2 % of patients who received 90 mg of ustekinumab and in 70.0 % who received etanercept ; 1.9 % , 1.2 % , and 1.2 % , respectively , had serious adverse events . Safety patterns were similar before and after crossover from etanercept to ustekinumab . CONCLUSIONS The efficacy of ustekinumab at a dose of 45 or 90 mg was superior to that of high-dose etanercept over a 12-week period in patients with psoriasis . ( Clinical Trials.gov number , NCT00454584 . Objective Assess ustekinumab efficacy ( week 24/week 52 ) and safety ( week 16/week 24/week 60 ) in patients with active psoriatic arthritis ( PsA ) despite treatment with conventional and /or biological anti-tumour necrosis factor ( TNF ) agents . Methods In this phase 3 , multicentre , placebo-controlled trial , 312 adults with active PsA were r and omised ( stratified by site , weight ( ≤100 kg/>100 kg ) ,  methotrexate use )  to ustekinumab 45 mg or 90 mg at week 0 , week 4 , q12 weeks or placebo at week 0 , week 4 , week 16 and crossover to ustekinumab 45 mg at week 24 , week 28 and week 40 . At week 16 , patients with < 5 % improvement in tender/swollen joint counts  entered blinded early escape ( placebo→45 mg , 45 mg→90 mg , 90 mg→90 mg ) . The primary endpoint was ≥20 % improvement in American College of Rheumatology ( ACR20 ) criteria at week 24 . Secondary endpoints included week 24 Health Assessment Question naire-Disability Index ( HAQ-DI ) improvement , ACR50 , ACR70 and ≥75 % improvement in Psoriasis Area and Severity Index ( PASI75 ) . Efficacy was assessed in all patients , anti-TNF-naïve ( n=132 ) patients and anti-TNF-experienced ( n=180 ) patients . Results More ustekinumab-treated ( 43.8 % combined ) than placebo-treated ( 20.2 % ) patients achieved ACR20 at week 24 ( p<0.001 ) . Significant treatment differences were observed for week 24 HAQ-DI improvement ( p<0.001 ) , ACR50 ( p≤0.05 ) and PASI75 ( p<0.001 ) ; all benefits were sustained through week 52 . Among patients previously treated with ≥1 TNF inhibitor , sustained ustekinumab efficacy was also observed ( week 24 combined vs placebo : ACR20 35.6 % vs 14.5 % , PASI75 47.1 % vs 2.0 % , median HAQ-DI change −0.13 vs 0.0 ; week 52 ustekinumab-treated : ACR20 38.9 % , PASI75 43.4 % , median HAQ-DI change −0.13 ) . No unexpected adverse events were observed through week 60 . Conclusions The interleukin-12/23 inhibitor ustekinumab ( 45/90 mg q12 weeks ) yielded significant and sustained improvements in PsA signs/symptoms in a diverse population of patients with active PsA , including anti-TNF-experienced PsA patients OBJECTIVE To evaluate the efficacy and safety of apremilast , a novel , orally available small molecule that specifically targets phosphodiesterase 4 , in the treatment of active psoriatic arthritis ( PsA ) . METHODS This phase II , multicenter , r and omized , double-blind , placebo-controlled study included the following : a 12-week treatment phase , with patients receiving placebo , apremilast 20 mg twice per day , or apremilast 40 mg once per day ; a 12-week treatment-extension phase , with patients in the placebo group re-r and omized to receive apremilast ; and a 4-week observational phase after treatment cessation . The primary end point was the proportion of patients achieving the American College of Rheumatology criteria for 20 % improvement ( ACR20 ) at week 12 . Safety assessment s included adverse events ( AEs ) , physical examinations , vital signs , laboratory parameters , and electrocardiograms . RESULTS Of the 204 patients with PsA who were r and omized to a treatment group , 165 completed the treatment phase . At the end of the treatment phase ( week 12 ) , 43.5 % of patients receiving apremilast 20 mg twice per day ( P < 0.001 ) and 35.8 % of those receiving 40 mg once per day ( P = 0.002 ) achieved an ACR20 response , compared with 11.8 % of those receiving placebo . At the end of the treatment-extension phase ( week 24 ) , > 40 % of patients in each group ( patients receiving apremilast 20 mg twice per day , patients receiving apremilast 40 mg once per day , and patients in the placebo group re-r and omized to receive apremilast ) achieved the ACR20 level of improvement . Most patients in the treatment phase ( 84.3 % ) and treatment-extension phase ( 68.3 % ) reported ≥ 1 AE . Diarrhea , headache , nausea , fatigue , and nasopharyngitis were reported most frequently ; most events were mild or moderate . No clinical ly relevant laboratory or electrocardiographic abnormalities were reported . CONCLUSION Treatment with apremilast at a dosage of 20 mg twice per day or 40 mg once per day demonstrated efficacy in comparison with placebo and was generally well tolerated in patients with active PsA. The balance of efficacy , tolerability , and safety supports further study of apremilast in BACKGROUND Many patients with psoriasis develop psoriatic arthritis , a chronic inflammatory disease that afflicts peripheral synovial , axial , and entheseal structures . The fully human monoclonal antibody ustekinumab is an efficacious treatment for moderate-to-severe plaque psoriasis . We did a r and omised , placebo-controlled , phase 3 trial to assess the safety and efficacy of ustekinumab in patients with active psoriatic arthritis . METHODS In this phase 3 , multicentre , double-blind , placebo-controlled trial at 104 sites in Europe , North America , and Asia-Pacific , adults with active psoriatic arthritis ( ≥5 tender and ≥5 swollen joints , C-reactive protein ≥3·0 mg/L ) were r and omly assigned ( 1:1:1 , by dynamic central r and omisation based on an algorithm implemented by an interactive voice-web response system ) to 45 mg ustekinumab , 90 mg ustekinumab , or placebo at week 0 , week 4 , and every 12 weeks thereafter . At week 16 , patients with less than 5 % improvement in both tender and swollen joint counts entered masked early-escape and were given 45 mg ustekinumab ( if in the placebo group ) or 90 mg ustekinumab ( if in the 45 mg group ) . At week 24 , all remaining patients in the placebo group received ustekinumab 45 mg , which they continued at week 28 and every 12 weeks thereafter . Our primary endpoint was 20 % or greater improvement in American College of Rheumatology ( ACR20 ) criteria at week 24 . This trial is registered with Clinical Trials.gov ( NCT01009086 ) and EudraCT ( 2009 - 012264 - 14 ) . FINDINGS Between Nov 30 , 2009 , and March 30 , 2011 , 615 patients were r and omly assigned-206 to placebo , 205 to 45 mg ustekinumab , and 204 to 90 mg ustekinumab . More ustekinumab-treated ( 87 of 205 [ 42·4 % ] in the 45 mg group and 101 of 204 [ 49·5 % ] in the 90 mg group ) than placebo-treated ( 47 of 206 [ 22·8 % ] ) patients achieved ACR20 at week 24 ( p<0·0001 for both comparisons ) ; responses were maintained at week 52 . At week 16 , proportions of patients with adverse events were similar in the ustekinumab and placebo groups ( 171 of 409 [ 41·8 % ] vs 86 of 205 [ 42·0 % ] ) . INTERPRETATION Ustekinumab significantly improved active psoriatic arthritis compared with placebo , and might offer an alternative therapeutic mechanism of action to approved biological treatments . FUNDING Janssen Research & Development Background : Secukinumab demonstrated superior efficacy to ustekinumab at week 4 and week 16 of the CLEAR study , with comparable safety , in subjects with moderate‐to‐severe plaque psoriasis . Objective : To compare the efficacy and safety of secukinumab and ustekinumab use over 52 weeks . Methods : Analysis of 52‐week data from CLEAR , a r and omized , double‐blind , phase 3b study . Results : Among 676 r and omized subjects , secukinumab demonstrated superiority to ustekinumab at week 52 in the proportion of subjects with ≥90 % improvement in Psoriasis Area and Severity Index ( PASI 90 ) ( 76 % vs 61 % [ P < .0001 ] ) ; PASI 100 responses were 46 % versus 36 % ( P = .0103 ) and Investigator 's Global Assessment responses of clear/almost clear skin were 80 % versus 65 % ( P < .0001 ) . Subjects on secukinumab  reported greater reductions in psoriasis‐related pain , itching , and scaling , and greater improvement across all quality ‐of‐life measures evaluated ( Dermatology Life Quality Index [ DLQI ] , EuroQoL 5‐Dimension Health Question naire , Work Productivity and Activity Impairment Question naire‐Psoriasis , and Health Assessment Question naire‐Disability Index ) . At week 52 , 72 % of subjects on secukinumab versus 59 % on ustekinumab ( P = .0008 ) reported no impact of skin disease on their lives ( DLQI 0/1 response ) . Safety and tolerability was comparable . Limitations : There was no placebo arm . Conclusion : In this head‐to‐head , double‐blind study , secukinumab demonstrated sustained superior efficacy in comparison with ustekinumab in clearing skin through week 52 , greater improvement in quality of life , and a favorable and comparable safety profile OBJECTIVE To investigate the efficacy and tolerability of infliximab therapy for the articular and dermatologic manifestations of active psoriatic arthritis ( PsA ) . METHODS One hundred four patients with PsA in whom prior therapy with at least 1 disease-modifying antirheumatic drug ( DMARD ) had failed were recruited into this investigator-initiated , multicenter , r and omized , double-blind , placebo-controlled clinical trial . During the initial blinded portion of the study , patients received infusions of infliximab ( 5 mg/kg ) or placebo at weeks 0 , 2 , 6 , and 14 . After week 16 , patients initially assigned to receive placebo crossed over to receive infliximab 5 mg/kg every 8 weeks through week 50 , while patients initially r and omized to infliximab continued to receive active treatment at the same dose through week 50 . The primary efficacy outcome was achievement of the American College of Rheumatology 20 % criteria for improvement in rheumatoid arthritis ( ACR20 ) at week 16 . Additional predefined clinical efficacy assessment s included the Psoriasis Area and Severity Index ( PASI ) score , the ACR50 and ACR70 criteria , the Disease Activity Score in 28 joints , the Health Assessment Question naire , ratings of enthesitis and dactylitis , and the Psoriatic Arthritis Response Criteria score . RESULTS The proportion of infliximab-treated patients who achieved an ACR20 response at week 16 ( 65 % ) was significantly higher than the proportion of placebo-treated patients who achieved this response ( 10 % ) . In addition , 46 % of infliximab-treated patients achieved an ACR50 response , and 29 % achieved an ACR70 response ; no placebo-treated patient achieved these end points . Among patients who had PASI scores of > /=2.5 at baseline , 68 % of infliximab-treated patients achieved improvement of > /=75 % in the PASI score at week 16 compared with none of the placebo-treated patients . Continued therapy with infliximab result ed in sustained improvement in articular and dermatologic manifestations of PsA through week 50 . The incidence of adverse events was similar between the treatment groups . CONCLUSION Therapy with infliximab at a dose of 5 mg/kg significantly improved the signs and symptoms of arthritis , psoriasis , dactylitis , and enthesitis in patients with active PsA that had been resistant to DMARD therapy . With continued infliximab treatment , benefits were sustained through 50 weeks . The benefit-to-risk ratio appeared favorable in this study population OBJECTIVE Etanercept has been shown to improve the articular and cutaneous manifestations of psoriatic arthritis ( PsA ) . In this study , we further evaluated the safety , efficacy , and effect on radiographic progression of etanercept in patients with PsA. METHODS Patients with PsA ( n = 205 ) were r and omized to receive placebo or 25 mg etanercept subcutaneously twice weekly for 24 weeks . Patients continued to receive blind-labeled therapy in a maintenance phase until all had completed the 24-week phase , then could receive open-label etanercept in a 48-week extension . Efficacy and safety were evaluated at 4 , 12 , and 24 weeks and at 12-week intervals thereafter . Radiographs of the h and s and wrists were assessed at baseline and 24 weeks , at entry to the open-label phase , and after 48 weeks in the study . RESULTS Etanercept significantly reduced the signs and symptoms of PsA and psoriasis . At 12 weeks , 59 % of etanercept patients met the American College of Rheumatology 20 % improvement criteria for joint response , compared with 15 % of placebo patients ( P < 0.0001 ) , and results were sustained at 24 and 48 weeks . At 24 weeks , 23 % of etanercept patients eligible for psoriasis evaluation achieved at least 75 % improvement in the Psoriasis Area and Severity Index , compared with 3 % of placebo patients ( P = 0.001 ) . Radiographic disease progression was inhibited in the etanercept group at 12 months ; the mean annualized rate of change in the modified total Sharp score was -0.03 unit , compared with + 1.00 unit in the placebo group ( P = 0.0001 ) . Etanercept was well tolerated . CONCLUSION Etanercept reduced joint symptoms , improved psoriatic lesions , inhibited radiographic progression , and was well tolerated in patients with OBJECTIVE To assess the efficacy and safety of golimumab in patients with active psoriatic arthritis ( PsA ) . METHODS Adult patients with PsA who had at least 3 swollen and 3 tender joints and active psoriasis were r and omly assigned to receive subcutaneous injections of placebo  ( n = 113 ) , golimumab 50 mg ( n = 146 ) , or golimumab 100 mg ( n = 146 ) every 4 weeks through week 20 . Efficacy assessment s through week 24 included the American College of Rheumatology 20 % improvement criteria ( ACR20 ) , the Psoriasis Area and Severity Index ( PASI ) in patients in whom at least 3 % of the body surface area was affected by psoriasis at baseline , the  Short Form 36 Health Survey ( SF-36 ) , the disability index of the Health Assessment Question naire ( HAQ ) , the Nail Psoriasis Severity Index ( NAPSI ) , the physician 's global assessment of psoriatic nail disease , and enthesitis ( using the PsA-modified Maastricht Ankylosing Spondylitis Enthesitis Score [ MASES ] index ) . RESULTS At week 14 , 48 % of all patients receiving golimumab , 51 % of patients receiving golimumab 50 mg , and 45 % of patients receiving golimumab 100 mg achieved an ACR20 response ( the primary end point ) , compared with 9 % of patients receiving placebo ( P < 0.001 for all comparisons ) . Among the 74 % of patients in whom at least 3 % of the body surface area was affected by psoriasis at baseline , 40 % of those in the golimumab 50 mg group and 58 % of those in the golimumab 100 mg group had at least 75 % improvement in the PASI at week 14 ( major secondary end point ) , compared with 3 % of placebo-treated patients ( P < 0.001 for both doses ) . Significant improvement was observed for other major secondary end points ( the HAQ and the SF-36 ) , the NAPSI , the physician 's global assessment of psoriatric nail disease , and the PsA-modified MASES index in each golimumab group compared with placebo . This efficacy was maintained through week 24 . Golimumab was generally well tolerated . CONCLUSION Treatment with golimumab at doses of 50 mg and 100 mg significantly improved active PsA and associated skin and nail psoriasis through week 24 Objective . Apremilast , an oral phosphodiesterase 4 inhibitor , downregulates intracellular inflammatory mediator synthesis by elevating cyclic adenosine monophosphate levels . The PALACE 2 trial evaluated apremilast efficacy and safety in patients with active psoriatic arthritis ( PsA ) despite prior conventional disease-modifying antirheumatic drugs and /or biologic therapy . Methods . Eligible patients were r and omized ( 1:1:1 ) to  placebo , apremilast 20 mg BID , or apremilast 30 mg BID . At Week 16 , patients with swollen and tender joint count improvement < 20 % entered early escape , with placebo patients rer and omized ( 1:1 ) to apremilast 20 mg BID or 30 mg BID while apremilast patients continued on their initial apremilast dose . At Week 24 , patients remaining on placebo were rer and omized to apremilast 20 mg BID or 30 mg BID . The primary endpoint was the proportion of patients achieving > 20 % improvement in American College of Rheumatology response criteria ( ACR20 ) at Week 16 . Results . In the intent-to-treat population ( N = 484 ) , ACR20 at Week 16 was achieved by more patients receiving apremilast 20 mg BID [ 37.4 % ( p = 0.0002 ) ] and 30 mg BID [ 32.1 % ( p = 0.0060 ) ] versus placebo ( 18.9 % ) . Clinical ly meaningful improvements in signs and symptoms of PsA , physical function , and psoriasis were observed with apremilast through Week 52 . The most common adverse events were diarrhea , nausea , headache , and upper respiratory tract infection . Diarrhea and nausea generally occurred early and usually resolved spontaneously with continued treatment . Laboratory abnormalities were infrequent and transient . Conclusion . Apremilast demonstrated clinical improvements in PsA for up to 52 weeks , including signs and symptoms , physical function , and psoriasis . No new safety signals were observed . Clinical Trials.gov identifier : NCT01212757 BACKGROUND Interleukin 17A is a proinflammatory cytokine that is implicated in the pathogenesis of psoriatic arthritis . We assessed the efficacy and safety of subcutaneous secukinumab , a human anti-interleukin-17A monoclonal antibody , in patients with psoriatic arthritis . METHODS In this phase 3 , double-blind , placebo-controlled study undertaken at 76 centres in Asia , Australia , Canada , Europe , and the USA , adults ( aged ≥18 years old ) with active psoriatic arthritis were r and omly allocated in a 1:1:1:1 ratio with computer-generated blocks to receive subcutaneous placebo or secukinumab 300 mg , 150 mg , or 75 mg once a week from baseline and then every 4 weeks from week 4 . Patients and investigators were masked to treatment assignment . The primary endpoint was the proportion of patients achieving at least 20 % improvement in the American College of Rheumatology response criteria ( ACR20 ) at week 24 . Analysis was by intention to treat . This study is registered with Clinical Trials.gov , number NCT01752634 . FINDINGS Between April 14 , and Nov 25 , 2013 , 397 patients were r and omly assigned to receive secukinumab 300 mg ( n=100 ) , 150 mg ( n=100 ) , 75 mg ( n=99 ) , or placebo ( n=98 ) . A significantly higher proportion of patients achieved an ACR20 at week 24 with secukinumab 300 mg ( 54 [ 54 % ] patients ; odds ratio versus placebo 6·81 , 95 % CI 3·42 - 13·56 ; p<0·0001 ) , 150 mg ( 51 [ 51 % ] patients ; 6·52 , 3·25 - 13·08 ; p<0·0001 ) , and 75 mg ( 29 [ 29 % ] patients ; 2·32 , 1·14 - 4·73 ; p=0·0399 ) versus placebo ( 15 [ 15 % ] patients ) . Up to week 16 , the most common adverse events were upper respiratory tract infections ( four [ 4 % ] , eight [ 8 % ] , ten [ 10 % ] , and seven [ 7 % ] with secukinumab 300 mg , 150 mg , 75 mg , and placebo , respectively ) and nasopharyngitis ( six [ 6 % ] , four [ 4 % ] , six [ 6 % ] , and eight [ 8 % ] , respectively ) . Serious adverse events were reported by five ( 5 % ) , one ( 1 % ) , and four ( 4 % ) patients in the secukinumab 300 mg , 150 mg , and 75 mg groups , respectively , compared with two ( 2 % ) in the placebo group . No deaths were reported . INTERPRETATION Subcutaneous secukinumab 300 mg and 150 mg improved the signs and symptoms of psoriatic arthritis , suggesting that secukinumab is a potential future treatment option for patients with this disorder . FUNDING Novartis
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