Showing papers by "Lluís Puig published in 2015"

Phase 3 Studies Comparing Brodalumab with Ustekinumab in Psoriasis

Abstract: BackgroundEarly clinical studies suggested that the anti–interleukin-17 receptor A monoclonal antibody brodalumab has efficacy in the treatment of psoriasis. MethodsIn two phase 3 studies (AMAGINE-2 and AMAGINE-3), patients with moderate-to-severe psoriasis were randomly assigned to receive brodalumab (210 mg or 140 mg every 2 weeks), ustekinumab (45 mg for patients with a body weight ≤100 kg and 90 mg for patients >100 kg), or placebo. At week 12, patients receiving brodalumab were randomly assigned again to receive a brodalumab maintenance dose of 210 mg every 2 weeks or 140 mg every 2 weeks, every 4 weeks, or every 8 weeks; patients receiving ustekinumab continued to receive ustekinumab every 12 weeks, and patients receiving placebo received 210 mg of brodalumab every 2 weeks. The primary aims were to evaluate the superiority of brodalumab over placebo at week 12 with respect to at least a 75% reduction in the psoriasis area-and-severity index score (PASI 75) and a static physician’s global assessment ...

Actinic keratosis with atypical basal cells (AK I) is the most common lesion associated with invasive squamous cell carcinoma of the skin

Abstract: Background Progression from actinic keratosis (AK) to invasive squamous cell carcinoma (iSCC) of the skin is thought to occur after the development of full thickness epidermal neoplasia, as in the classic pathway of cervical cancer. Nevertheless, cutaneous iSCC may also directly arise from a proliferation of atypical basaloid cells limited mostly to the epidermal basal layer (AK I), akin to what happens in the ‘differentiated pathway’ of iSCC of the vulva, oral cavity and other locations. Objective To evaluate the prevalence of classic and differentiated pathways in the development of cutaneous iSCC. Methods The epidermis adjacent to and overlying iSCC, assumed to be representative of pre-existing lesions, was histologically studied in 196 skin biopsy specimens showing iSCC. Results AK I, AK II and AK III lesions overlying iSCC were present in 63.8%, 17.9% and 18.4% of cases respectively. The corresponding percentages in the epidermis adjacent to iSCC were 77.9%, 6.6% and 8.3% respectively (stage could not be assessed in 8.1% of cases). Focal epidermal ulceration overlying iSCC was seen in 32% of AK I, 28.6% of AK II and 33.3% of AK III instances. Adnexal involvement by atypical keratinocytes (proliferative AK) was present more frequently in cases with overlying AK I (39/125, 31.2%) than with AK II (8/35, 22.9%) and AKII I (5/36, 13.9%). Conclusion Direct invasion from proliferating basaloid atypical keratinocytes limited to the epidermal basal layer (AK I), known as the differentiated pathway, was the most common form of progression to cutaneous iSCC in our series. On the other hand, stepwise progression from AK I to AK II and AK III (classic pathway) was seen to be operative in a substantial proportion of iSCC cases. All AK lesions, irrespective of intraepidermal neoplasia thickness, are therefore potentially invasive and tumour advance along adnexal structures might facilitate iSCC development from AK I lesions.

PASI90 response: the new standard in therapeutic efficacy for psoriasis

Abstract: In a non-life-threatening disease such as psoriasis, treatment goals should be referred to the improvement in severity and extent of the disease and their impact on patients' perceived health-related quality of life (HRQoL), usually measured by the Dermatology Life Quality Index (DLQI). The ultimate goal of therapy is blanching, and an improvement of 90% or better (PASI90 response) with respect to baseline Psoriasis Area and Severity Index (PASI) is considered as treatment success by the European Medicines Agency. PASI75 response has become accepted as a less stringent reasonable therapeutic goal, but absolute PASI values might provide a better benchmark, irrespective of baseline PASI. Anyway, objective measures of psoriasis involvement are clinically meaningful only if they correlate with significant improvements in DLQI, and especially with the achievement of a DLQI = 0-1 status, corresponding to lack of effect of the disease on patient's HRQoL. Even though PASI75 response meets therapeutic expectations in most patients, PASI90 response or better has a significantly higher impact on DLQI improvement and is associated with significantly higher DLQI = 0-1 response rates. The introduction of anti-IL17 drugs in clinical practice bears the promise of achieving PASI90 response or better in the majority of patients, and initial data suggest that the PASI90 benchmark provides better discriminatory value as regards achievement of DLQI = 0-1 response. Further research is required to confirm the value of absolute PASI cut-offs as a measure of therapeutic success independent of baseline and duration of treatment, and to develop newer, more practical and more accurate measures of psoriasis severity.

Physician perspectives in the management of psoriasis and psoriatic arthritis: results from the population-based Multinational Assessment of Psoriasis and Psoriatic Arthritis survey

Abstract: BACKGROUND: Available literature on psoriasis and psoriatic arthritis (PsA) demonstrates a tremendous burden of disease and suggests underdiagnosis and undertreatment. OBJECTIVE: To obtain real-world physician perspectives on the impact of psoriasis and PsA and its treatment on patients' daily lives, including perceptions of, and satisfaction with, current therapies. METHODS: The Multinational Assessment of Psoriasis and Psoriatic Arthritis (MAPP) surveyed dermatologists (n = 391) and rheumatologists (n = 390) in North America (Canada and the United States) and Europe (France, Germany, Italy, Spain and United Kingdom). RESULTS: Dermatologists classified 20.3% and 25.7% of their patients as having severe psoriasis and severe PsA respectively; rheumatologists indicated that 48.4% of their PsA patients had active disease. Of the psoriasis patients complaining of joint pain, only 33.0% had a diagnosis of PsA. An impact on daily activities or social/emotional well-being was recognized by 57.2% to 79.3% of physicians. In patients with moderate-to-severe psoriasis, dermatologists reported 74.9% were receiving topical therapy, 19.5% conventional oral therapy and 19.6% biologics. Dermatologists and rheumatologists reported similar rates of topical ( approximately 45%) and biologic ( approximately 30%) therapy utilization for their PsA patients; conventional oral therapy was more often prescribed by rheumatologists (63.4%) vs. dermatologists (35.2%). Reasons for not initiating or maintaining systemic therapies were related to concerns about long-term safety, tolerability, efficacy and costs (biologics). CONCLUSION: Physicians in North America and Europe caring for patients with psoriasis and PsA acknowledge unmet treatment needs, largely concerning long-term safety/tolerability and efficacy of currently available therapies; evidence suggests underdiagnosis of PsA and undertreatment of psoriasis among dermatologists.

Maintenance of Clinical Efficacy and Radiographic Benefit Through Two Years of Ustekinumab Therapy in Patients With Active Psoriatic Arthritis: Results From a Randomized, Placebo-Controlled Phase III Trial.

Abstract: Objective To evaluate the efficacy and safety of ustekinumab through 2 years in adult patients with active psoriatic arthritis (PsA). Methods A total of 615 adult patients with active PsA were randomized to placebo, ustekinumab 45 mg, or ustekinumab 90 mg, at weeks 0, 4, and every 12 weeks through week 88 (last dose). At week 16, patients with <5% improvement in both tender and swollen joint counts entered blinded early escape (placebo to 45 mg, 45 mg to 90 mg, and 90 mg to 90 mg). All remaining placebo patients crossed over to ustekinumab 45 mg at week 24. Clinical efficacy measures included American College of Rheumatology criteria for 20% improvement (ACR20), Disease Activity Score in 28 joints using the C-reactive protein level (DAS28-CRP), and ≥75% improvement in the Psoriasis Area and Severity Index (PASI75). Radiographic progression was evaluated using the modified Sharp/van der Heijde score (SHS). Results At week 100, ACR20, DAS28-CRP moderate/good response, and PASI75 rates ranged from 56.7–63.6%, 71.9–76.7%, and 63.9–72.5%, respectively, across the 3 treatment groups. In both ustekinumab groups, the median percent improvement in dactylitis and enthesitis was 100% at week 100. The mean changes in SHS score from week 52 to week 100 were similar to those observed from week 0 to week 52 in the ustekinumab groups. Through week 108, 70.7% and 9.7% of patients had an adverse event (AE) or serious AE, respectively. The rates and type of AEs were similar between the dose groups. Conclusion Clinical and radiographic benefits from ustekinumab treatment were maintained through week 100 in the PSUMMIT 1 study. No unexpected safety events were observed; the safety profile of ustekinumab in this population was similar to that previously observed in psoriasis patients treated with ustekinumab.

Systemic methotrexate for the treatment of psoriasis

Abstract: In the era of biologic therapies, methotrexate (MTX), a classic immunomodulator, is still the cornerstone of systemic treatment of psoriasis. MTX has been used for many years, achieving good responses with a good safety profile. However, only a few randomized clinical trials have been performed involving MTX, and most of the current evidence comes from pivotal studies of biologic drugs. The aim of this article is to make an extensive review of the MTX mechanism of action, pharmacokinetics, efficacy, safety and tolerability, especially focusing on the future perspective of this old drug and recent advances in the field of pharmacogenetics.

Early intervention in psoriasis and immune-mediated inflammatory diseases: A hypothesis paper

Abstract: Psoriasis is an immune-mediated inflammatory disease (IMID) which may have a major impact on a patient's life, especially when the disease is moderate to severe. There is evidence that treatment of psoriasis during the first years is conservative and frequently based on topical agents which rarely clear lesions. Treatment with systemic agents including biologics is often undertaken only when topical agents have proved unsuitable, even in patients with moderate to severe disease. However, there is evidence that in other IMIDs (rheumatoid arthritis and Crohn's disease), targeted systemic treatment given early in the treatment pathway may improve long-term patient outcomes. We hypothesize that a patient-centered therapeutic approach, undertaken early in the psoriasis treatment pathway ("early intervention") with the goal of complete clearance, may improve control of cutaneous symptoms and may also modify disease course and burden. Critical points to address when designing an early intervention study would include: the definition of psoriasis disease activity; patient selection; intervention selection; and dosing strategies.

Long-term efficacy, safety and drug survival of ustekinumab in a Spanish cohort of patients with moderate to severe plaque psoriasis.

Abstract: Objective: To investigate the efficacy and safety of ustekinumab in clinical practice and the influence of several variables on response rates as well as on drug

Association of the PDE3A-SLCO1C1 locus with the response to anti-TNF agents in psoriasis.

Abstract: Psoriasis is a prevalent autoimmune disease of the skin that causes significant psychological and physical disability. Tumor necrosis factor (TNF)-blocking agents have proven to be highly efficacious in the management of moderate-to-severe psoriasis. However, a significant percentage of patients do not respond to this treatment. Recently, variation at the PDE3A-SLCO1C1 (phosphodiesterase 3A-SoLute Carrier Organic anion transporter family member 1C1) locus has been robustly associated with anti-TNF response in rheumatoid arthritis. Using a cohort of 130 psoriasis patients treated with anti-TNF therapy, we sought to analyze the association of this locus with treatment response in psoriasis. We found a highly significant association between PDE3A-SLCO1C1 and the clinical response to TNF blockers (P=0.0031). Importantly, the allele that was previously associated with the lack of response to rheumatoid arthritis (G allele, single-nucleotide polymorphism rs3794271) was associated with a higher anti-TNF efficacy in psoriasis. The results of this study are an important step in the characterization of the pharmacogenetic profile associated with anti-TNF response in psoriasis.

A deletion at ADAMTS9-MAGI1 locus is associated with psoriatic arthritis risk

Abstract: Objective Copy number variants (CNVs) have been associated with the risk to develop multiple autoimmune diseases. Our objective was to identify CNVs associated with the risk to develop psoriatic arthritis (PsA) using a genome-wide analysis approach. Methods A total of 835 patients with PsA and 1498 healthy controls were genotyped for CNVs using the Illumina HumanHap610 BeadChip genotyping platform. Genomic CNVs were characterised using CNstream analysis software and analysed for association using the χ 2 test. The most significant genomic CNV associations with PsA risk were independently tested in a validation sample of 1133 patients with PsA and 1831 healthy controls. In order to test for the specificity of the variants with PsA aetiology, we also analysed the association to a cohort of 822 patients with purely cutaneous psoriasis (PsC). Results A total of 165 common CNVs were identified in the genome-wide analysis. We found a highly significant association of an intergenic deletion between ADAMTS9 and MAGI1 genes on chromosome 3p14.1 (p=0.00014). Using the independent patient and control cohort, we validated the association between ADAMTS9-MAGI1 deletion and PsA risk (p=0.032). Using next-generation sequencing, we characterised the 26 kb associated deletion. Finally, analysing the PsC cohort we found a lower frequency of the deletion compared with the PsA cohort (p=0.0088) and a similar frequency to that of healthy controls (p>0.3). Conclusions The present genome-wide scan for CNVs associated with PsA risk has identified a new deletion associated with disease risk and which is also differential from PsC risk.

Secukinumab (AIN457) for the treatment of psoriasis.

Abstract: Psoriasis is a chronic inflammatory disease with a multifactorial origin that appears in patients with genetic predisposition and is induced by environmental factors, and characterized by alterations in the innate and adaptive immunity. IL-17A is one of the specific cytokines involved in the pathogenesis of psoriasis and its inhibition is highly effective in the treatment of patients with moderate and severe psoriasis. Secukinumab is a monoclonal antibody that specifically binds to IL-17A and inhibits the interaction to its receptor, and it has demonstrated its efficacy and safety in the treatment of psoriasis. Phase II and III clinical trials indicate that > 80% of the patients receiving secukinumab achieve Psoriasis Area Severity Index (PASI) 75 at week 12. In the Phase III efficacy of response and safety of two fixed secukinumab regimens in psoriasis trial, PASI 75 rates were 81.6% with 300 mg secukinumab, 71.6% with 150 mg secukinumab and 4.5% with placebo, and responses were maintained up to 52 weeks in the majority of patients. In the Phase III Full Year Investigative Examination Of Secukinumab versus Etanercept Using Two Dosing Regimens To Determine Efficacy in Psoriasis study, the efficacy of secukinumab was compared to etanercept. The results indicate that both doses of secukinumab (150 and 300 mg) showed superior efficacy compared with etanercept throughout the study; PASI 75 rates at week 12 were 77.1% with 300 mg secukinumab, 67% with 150 mg of secukinumab, 44% with etanercept and 4.9% with placebo. PASI 90 and PASI 100 were 54 and 24% with secukinumab 300 mg and 21 and 4% with etanercept at week 12. At week 52, PASI 90 continued to be higher in the secukinumab group (65%) compared with the etanercept group (33%). Regarding safety, the most common side effects were nasopharyngitis and headache. The rate of infections was higher with secukinumab than placebo. This was especially the case for Candida infections, which were more common in the secukinumab group (4.7% with secukinumab 300 mg and 2.3% with secukinumab 150 mg), but all cases were resolved with conventional treatment. Secukinumab is a well-tolerated treatment that has demonstrated efficacy in treating moderate-to-severe plaque psoriasis. Nevertheless, long-term studies are necessary to confirm Phase II and Phase III data.

Efficacy of a fixed combination of calcipotriol/betamethasone dipropionate topical gel in adult patients with mild to moderate psoriasis: blinded interim analysis of a phase IV, multicenter, randomized, controlled, prospective study.

Abstract: BACKGROUND: Psoriasis is a common, chronic, inflammatory skin disease with the majority of individuals having limited disease, treated with topical medication. However, special attributes of topical treatments like galenic/cosmetic properties or an inconvenient treatment schedule may result in low preference for topical treatments. Hence, there is strong medical need for a topical medication, which is highly efficacious, easy-to-use and preferred by both physicians and patients. OBJECTIVE: Blinded interim analysis with the purpose to assess efficacy of (both from the physician's and patient's perspective) and the patients' preference with a highly efficacious and easy-to-use fixed combination of calcipotriol/betamethasone dipropionate topical gel after 8 weeks of once daily treatment in a large patient population. METHODS: In this phase IV, international, multicentre, randomized, controlled, prospective, parallel group study, adult patients with active, mild to moderate psoriasis despite previous topical psoriasis treatment, i.e. unsuccessful in the 8 weeks preceding study participation, are followed over 64 weeks. During the first 8 weeks the patients apply their medication once a day followed by a 56-weeks maintenance period according to SmPC. Blinded interim analysis of all patients included demographics, Physician's Global Assessment, the novel Patient's self Global Assessment (PsGA) and Patient Preference Questionnaire (PPQ). RESULTS: 1795 patients were analysed. At week 8, 36.5% of the physicians rated the patients' psoriasis as clear/almost clear. Similarly, based on the patients' self-assessment, 34.2% had a clear/almost clear score of PsGA in week 8. Analysis of the PPQ showed that the vast majority of the patients judged their 8-week treatment to be preferable compared with their previous treatments. CONCLUSION: Results of this blinded interim analysis indicate that the fixed combination of calcipotriol/betamethasone dipropionate gel is highly efficacious and preferred by the majority of analysed patients.

Improving patient outcomes in psoriasis: strategies to ensure treatment adherence

Abstract: Psoriasis is a frequent inflammatory disease with a chronic and relapsing course. Therefore, patients with psoriasis are likely to undergo different treatments for long periods of time. Traditionally, therapies used in psoriasis have been associated with poor levels of adherence due to the complexity of the regimens and the poor results obtained with the topical therapies. These poor outcomes are associated with high levels of frustration and anxiety, which decrease adherence and worsen the disease. With the recent introduction of highly efficacious biologic therapies, patients can achieve very good and prolonged responses. However, most patients with psoriasis have mild disease and may be treated with skin-directed therapies. Therefore, it is important to develop strategies to improve adherence in order to achieve better outcomes, and to improve the overall quality of life. Hence, acknowledging the causes of nonadherence is crucial for implementing these strategies. In this summary, we review the causes of nonadherence, and we provide behavioral strategies in order to improve adherence and, ultimately, the outcome of patients with psoriasis.

OP0174 Efficacy and Safety of Ustekinumab in Psoriatic Arthritis Patients with Spondylitis and Peripheral Joint Involvement: Results from a Phase 3, Multicenter, Double-Blind, Placebo-Controlled Study

Abstract: Background IL-23 may be implicated in spondylitis. A substantial number of pts with spondylitis and peripheral joint involvement were enrolled in PSUMMIT. Objectives We evaluated the efficacy of SC UST 45/90 mg in a subgroup of psoriatic arthritis (PsA) pts with physician diagnosed spondylitis and peripheral joint involvement through wk108, from PSUMMIT 1. Methods Adult PsA patients (n=615) with active disease (≥5 SJC and ≥5 TJC;CRP≥0.3mg/dL) despite DMARD and/or NSAIDs were randomized to UST45mg, 90mg, or PBO at wks 0, 4, and q12wks. Pts treated with prior anti-TNF agents were excluded. Stable concomitant MTX was permitted but not mandated. At wk16, pts with Results 186 randomized pts (70 PBO, 116 UST combined) had spondylitis with peripheral joint involvement at baseline (30% of overall population); mean baseline characteristics were similar to the overall population (age 45.6yrs, weight 82.8kg, PsA duration 6.3yrs, SJC/TJC 14.3/24.1, HAQ-DI 1.3; BASDAI 6.5, and 26% were HLAB27 positive. Mean baseline scores among pts with dactylitis (n=100), enthesitis (148), and skin disease (147) were 8.3, 5.6, and PASI 14.2, respectively. At wk24, greater proportions of combined UST45/90mg treated pts had improvements in dactylitis/enthesitis measurements, HAQ-DI and ACR20/50/70 responses than PBO (Table). Clinical improvements were generally maintained through wk100. A significantly higher proportion of UST-treated pts achieved BASDAI20/50/70 responses vs. PBO at wk24 (54.1%/27.9%/14.4% vs. 26.2%/13.1%/0.0%). Peripheral structural damage assessed by total vdH-S mean change from baseline also showed improvement in the UST groups vs PBO at wk24. Of the 135 patients with ≥3% BSA involvement and spondylitis with peripheral arthritis at baseline, PASI75 responses were also maintained through wk100. During the PBO-controlled period, the proportion of pts with AEs were comparable between the PBO and combined UST-treated groups (AEs 32.9% vs 24.1%; SAEs 1.4% vs 0.9%; discontinuations due to AEs 2.9% vs 0.9%; serious infections 14.3% vs 7.8%). Through 2yrs, safety observations were consistent with the overall PsA population. Conclusions In this post-hoc subgroup analysis, UST significantly improved signs and symptoms, and demonstrated improvements in BASDAI and peripheral radiographic progression compared with PBO through wk24; efficacy was maintained through wk100. UST was well-tolerated and demonstrated a safety profile similar to that observed in the overall PsA study population. Disclosure of Interest A. Kavanaugh Grant/research support from: AbbVie, Amgen, Janssen, and UCB., L. Puig Grant/research support from: AbbVie, Amgen, Boehringer, Celgene, Eli Lilly, Janssen, Leo-Pharma, Merck/Schering-Plough, Merck-Serono, Novartis, Pfizer, Sandoz, and VBL., A. Gottlieb Grant/research support from: Amgen, AbbVie, Celgene, Coronado, Eli Lilly, Janssen, Levia, Merck, and Pfizer., Consultant for: AbbVie, Actelion, Akros, Amgen, Astellas, Bristol Myers Squibb, Canfite, Catabasis, Celegene, CSL Behring Biotherapies for Life, Coronado, Dermipsor, Eli Lilly, GlaxoSmithKline, Incyte, Janssen, Karyopharm, Novartis, Novo Nordisk, Pfizer, Sanofi Aventix, UCB, Vertex, and Xenoport., C. Ritchlin Grant/research support from: Amgen, Janssen, and UCB., Consultant for: AbbVie, Amgen, Janssen, Regeneron, Roche, and UCB., Y. You Employee of: Janssen R&D, LLC., Y. Wang Employee of: Janssen R&D, LLC., A. Mendelsohn Employee of: Janssen R&D, LLC., M. Song Employee of: Janssen R&D, LLC., P. Rahman Grant/research support from: AbbVie, Amgen, Janssen, Pfizer, and Novartis., I. McInnes Grant/research support from: AbbVie, BMS, Janssen, Pfizer, Roche, Merck/Schering-Plough, and UCB.

Long-term (1 year) efficacy of etanercept in moderate-to-severe psoriasis. Results of a multicentric observational study in Spain

Abstract: Information on the long-term efficacy of etanercept (ETN) treatment of moderate-to-severe psoriasis according to the Summary of Product Characteristics (SmPC) is scarce. We report the efficacy results of an observational clinical trial including 202 patients treated for 12 months with ETN according to SmPC. Concomitant topical treatment was permitted throughout the study period. Efficacy assessment was done by intention-to-treat analysis with last observation carried forward. Mean%Body Surface Area (BSA) and Psoriasis Area and Severity Index (PASI) decreased from 39.0% and 22.2% at baseline to 7.9% and 4.4%, respectively, at 12 months. Throughout the study duration, PASI 50, PASI 75 and PASI 90 response rates ranged from 72.8% to 95.7%, 55.6% to 84.3%, and 36.1% to 62.2%, respectively. Body mass index and body weight had minor effects on treatment efficacy. ETN treatment according to the SmPC provided sustained improvement of psoriasis throughout one year.

A new score assessing the surgical wound of a TKA and its relation with pain, infection and functional outcome.

Abstract: The aim of this study was to describe a new score to measure the aspect of the TKA surgical wound and to correlate it with postoperative pain, infection and functional outcomes at 1 year of follow-up. This score, ranging from 0 to 10, assessed 5 parameters; swelling, haematoma, erythema, blood draining and blisters. 159 consecutive TKA were prospectively evaluated. Intra and inter-rate reliability was superior to 0.9. No differences were obtained comparing the aspect of the surgical wound with postoperative pain or functional outcomes. Incidence of deep infection is directly related with an increased score (p=0.0025).

THU0419 Integrated Safety of Ustekinumab in Psoriatic Arthritis: 2 Year Follow-Up from the Psoriatic Arthritis Clinical Development Program

Abstract: Objectives To report the safety of ustekinumab (UST) from the psoriatic arthritis (PsA) development program. Methods Safety data through up to 2yrs of follow-up were pooled from Ph3 for the analysis of overall safety endpoints. Data were pooled from Ph2 (n=146) and Ph3 for AEs of interest. In Ph3, adult PsA pts (PSUMMIT I [n=615], PSUMMIT II [n=312]) with active disease (≥5 SJC and ≥5 TJC; CRP≥0.3mg/dL [ULN 1.0 mg/dL]) despite DMARD and/or NSAID or previously treated with DMARD and/or NSAID, and prior anti-TNFα therapy (PSUMMIT II only) were randomized to UST45mg, 90mg, or PBO at wks 0, 4, and q12wks; at wk16, pts with Results 379 and 1018 pts were treated with PBO and UST, resp, for up to 2yrs (duration of follow-up: Ph2 36wks, PSUMMIT1 108wks, and PSUMMIT2 60wks) with 145 PY and 1403 PY overall for the PBO and UST grps, resp. At baseline, 96.8% were white, 52.2% male, mean age 47.6yrs (SD 11.8). Mean BMI was 30.9 kg/m 2 (SD 7.1), mean PsA and PsO duration was 7.2 yrs (SD 7.7) and 15.8yrs (SD 12.6), resp. Safety outcomes are detailed in Table 1. Event rates of overall AEs, infections, and SAEs, were comparable among PBO and UST during the PBO-controlled period; rates remained comparable through 2yrs of follow-up. Rates of AEs leading to d/c were higher in PBO. Overall AE rates were not impacted by baseline MTX or prior anti-TNF usage. 1 squamous cell carcinoma (90mg), 1 serious infection (PBO) and 1 MI (PBO) were reported during PBO-controlled period. With up to 2yrs of follow-up, rate of infections was similar in 90mg vs 45mg grps; serious infections were numerically greater in the 90mg vs 45 mg grp (2.1/100PY [95% CI:1.1,3.5] vs 0.5/100PY [95% CI: 0.1,1.3], resp), and included 2 pts in the 90mg grp with multiple events (most were single events without apparent trend). 4 non-melanoma skin cancers (NMSC)(0.64/100PY) occurred in the 90mg grp and no NMSCs occurred in the 45mg grp. 3 malignancies (0.4/100PY), other than NMSC, occurred in 45mg grp and none in 90mg grp. Major adverse cardiovascular event (MACE) rates were low and no dose effects were observed (1.15 vs 0.24 for 45mg and 90mg, resp). No cases of active TB or serious opportunistic infections, RPLS, demyelination, anaphylaxis or serum sickness-like reactions were reported. Conclusions Pooled safety data show that UST was well tolerated at both doses with up to 2yrs of follow-up without new safety signals. The safety profile of UST in the PsA clinical development program was generally comparable to that observed in the psoriasis population. Disclosure of Interest A. Kavanaugh Grant/research support from: AbbVie, Amgen, Janssen, and UCB., I. McInnes Grant/research support from: AbbVie, BMS, Janssen, Pfizer, Roche, Merck/Schering-Plough, and UCB., C. Ritchlin Grant/research support from: Amgen, Janssen, and UCB, Consultant for: AbbVie, Amgen, Janssen, Regeneron, Roche, and UCB., P. Rahman Grant/research support from: AbbVie, Amgen, Janssen, Pfizer, and Novartis., L. Puig Grant/research support from: AbbVie, Amgen, Boehringer, Celgene, Eli Lilly, Janssen, Leo-Pharma, Merck/Schering-Plough, Merck-Serono, Novartis, Pfizer, Sandoz, and VBL., A. Gottlieb Grant/research support from: Amgen, AbbVie, Celgene, Coronado, Eli Lilly, Janssen, Levia, Merck, and Pfizer, Consultant for: AbbVie, Actelion, Akros, Amgen, Astellas, Bristol Myers Squibb, Canfite, Catabasis, Celegene, CSL Behring Biotherapies for Life, Coronado, Dermipsor, Eli Lilly, GlaxoSmithKline, Incyte, Janssen, Karyopharm, Novartis, Novo Nordisk, Pfizer, Sanofi Aventix, UCB, Vertex, and Xenoport., M. Song Employee of: Janssen R&D, LLC., B. Randazzo Employee of: Janssen R&D, LLC., S. Li Employee of: Janssen R&D, LLC., Y. You Employee of: Janssen R&D, LLC., A. Mendelsohn Employee of: Janssen R&D, LLC.

SAT0563 Long Term Improvements in Physical Function are Associated with Improvements in Dactylitis, Enthesitis, Tender and Swollen Joint Counts, and Psoriasis Skin Involvement: Results from a Phase 3 Study of Ustekinumab in Psoriatic Arthritis Patients

Abstract: Objectives To evaluate the association of improvements in tender and swollen joint counts (TJC, SJC), psoriasis skin involvement, and dactylitis/enthesitis (in patients affected at baseline) with improvement in physical function using data from the ustekinumab (UST) PSUMMIT 1 trial in psoriatic arthritis (PsA) pts. Methods Adult PsA pts (n=615) with active disease (≥5 SJC and ≥5 TJC; CRP ≥0.3 mg/dL) despite DMARD and/or NSAIDs were randomized to UST45mg, 90mg, or PBO at wks 0, 4, and q12wks. Pts treated with prior anti-TNF agents were excluded. Stable concomitant MTX was permitted but not mandated. At wk16, pts with Results At baseline, mean (median) TJC and SJC values were 23.5 (20.0) and 13.5 (10.0), respectively. 441 (71.7%) and 296 (48.1%) patients had enthesitis or dactylits at baseline, respectively; 440 (71.7%) patients had >3% BSA psoriasis skin involvement. Improvements in TJC, SJC, dactylitis and enthesitis, and PASI scores were generally greater in HAQ responders compared with HAQ non-responders at both wk52 and wk100 (Table). Significant correlations were demonstrated between the HAQ change from baseline with percent change in outcomes parameters for all outcomes (Table) at wk52 and wk100. In addition, associations were observed at earlier time points at wk24/wk28 [TJC -0.39/-0.36; SJC -0.27/-0.20; enthesitis 0.30/0.28 (all p Conclusions Based on this post-hoc analysis of the PSUMMIT 1 population, improvements in physical function as measured by HAQ were associated with improvements in TJC, SJC, dactylitis and enthesitis, and these correlations were observed as early as week 24 and continued through week100. Improvement in skin disease was also associated with improvements in HAQ. Disclosure of Interest A. Kavanaugh Grant/research support from: AbbVie, Amgen, Janssen, and UCB., L. Puig Grant/research support from: AbbVie, Amgen, Boehringer, Celgene, Eli Lilly, Janssen, Leo-Pharma, Merck/Schering-Plough, Merck-Serono, Novartis, Pfizer, Sandoz, and VBL, A. Gottlieb Grant/research support from: Amgen, AbbVie, Celgene, Coronado, Eli Lilly, Janssen, Levia, Merck, and Pfizer., Consultant for: AbbVie, Actelion, Akros, Amgen, Astellas, Bristol Myers Squibb, Canfite, Catabasis, Celegene, CSL Behring Biotherapies for Life, Coronado, Dermipsor, Eli Lilly, GlaxoSmithKline, Incyte, Janssen, Karyopharm, Novartis, Novo Nordisk, Pfizer, Sanofi Aventix, UCB, Vertex, and Xenoport., C. Ritchlin Grant/research support from: Amgen, Janssen, and UCB, Consultant for: AbbVie, Amgen, Janssen, Regeneron, Roche, and UCB., S. Li Employee of: Janssen R&D, LLC., Y. You Employee of: Janssen R&D, LLC., A. Mendelsohn Employee of: Janssen R&D, LLC., M. Song Employee of: Janssen R&D, LLC., P. Rahman Grant/research support from: AbbVie, Amgen, Janssen, Pfizer, and Novartis., I. McInnes Grant/research support from: AbbVie, BMS, Janssen, Pfizer, Roche, Merck/Schering-Plough, and UCB

Chronic Ulceration and Fibrosis of the Forearm

Abstract: Awhiteman inhis30switha7-yearhistoryof severe,mechanical, lowbackpain and longstandingmental depressionwas referred to thedermatologydepartment for evaluationof an asymptomatic cutaneous ulcer that had developed over the past year. Physical examinationdisclosed a large anddeep, irregularly shaped, cutaneous ulcer on thedorsumof his right forearm.Necrotic tissueandmuscleexposurewasseenat thebaseof theulcer (Figure, A). Woody induration of skin on both forearms and on the abdominal region was also observed. Bilateral contracture of deltoid, triceps, and bicepsmuscles was noted. Active and passive range of motion was restricted at the shoulders and elbows. No signs of joint inflammation were seen. At the time of consultation, the patient was taking oral treatment with duloxetine hydrochloride, clonazepam, oxcarbazepine, fentanyl, sulpiride, zopiclone, omeprazolemagnesium, and baclofen. He also admitted to self-administering subcutaneous injectionsofmeperidine, 100mg4 timesperday, for thepast 3 years, at different sites, including the deltoid areas and abdomen. Growth from culture specimens taken from the ulcer was negative for bacteria, mycobacteria, and fungal organisms. His serum creatinine kinase level was raised (192 U/L; reference range, 0-174 U/L), but test results for complete blood cell count; erythrocyte sedimentation rate; antinuclear antibody, rheumatoid factor, aspartateaminotransferase,alanineaminotransaminase,andaldolase levels;andserumelectrophoresis were all within normal limits. A wedge biopsy from the indurated skin of the abdominal regionwas performed (Figure, B andC). (To convert creatinine kinase tomicrokatals per liter, multiply by 0.0167.) A

Doubtful Role of IL28B Polymorphism in Occult Hepatitis B Infection.

Abstract: Aims: To investigate the influence of IL28B polymorphism in occult hepatitis B infection (OBI) and whether IL28B genetic variants are associated with hepatitis B virus (HBV)-specific T-cell responses. Patients and Methods: The rs12979860 IL28B genotype was determined in 34 OBI blood donors, 22 spontaneous HBV resolvers, 36 inactive HBV carriers and 25 seronegative donors. T-cell responses to HBV recombinant proteins were assessed by interferon-γ enzyme-linked immunospot assay. Results: The frequency of the IL28B CC genotype among OBI patients was similar to that of inactive carriers [41 vs. 39%, respectively, p = 0.961; odds ratio (OR) = 1.10; 95% confidence interval (CI) = 0.42-2.86; p = 0.845]. The IL28B CC genotype was found more frequently in spontaneous resolvers, although the differences were not significant (45 vs. 39%, spontaneous resolvers and inactive carriers, respectively; p = 0.828; OR = 1.31; 95% CI = 0.45-3.83; p = 0.622). HBV-specific T-cell responses were detected in OBIs, and significantly stronger T-cell responses towards hepatitis B envelope antigen were observed in those with the IL28B CC genotype. In spontaneous resolvers and inactive carriers, IL28B CC did not correlate with the magnitude of T-cell responses. Conclusions: In OBI donors, IL28B CC correlates with the intensity of HBV-specific T-cell responses. In this study, IL28B CC is not statistically associated with OBI or with HBV clearance, but a larger number of cases is needed before completely ruling out its role in HBV infection.

Onychomadesis and Pyogenic Granulomas After Postoperative Upper-Limb Immobilization

Abstract: Se han descrito numerosas alteraciones ungueales secundarias a intervenciones quirurgicas, especialmente en relacion con inmovilizaciones prolongadas. Presentamos el caso de un paciente con onicomadesis y granulomas piogenicos tras la inmovilizacion con una escayola de la extremidad superior despues de una intervencion quirurgica. Se trata de un varon de 35 anos, alergico a la penicilina y derivados, sin otros antecedentes personales de interes, que acudio a consultas externas de dermatologia por presentar alteraciones ungueales de 2 meses de evolucion. A la exploracion fisica se objetivaron nodulos eritematosos de aspecto vascular en los pliegues ungueales proximales del 2. y 4. dedos de la mano izquierda, con desprendimiento total proximal de las laminas ungueales de los dedos 2. a 5. de esa misma mano (fig. 1). No presentaba lesiones contralaterales. No referia fiebre, dolor, aumento de sudoracion, parestesias, ni ninguna otra sintomatologia