Effects of Disease-Worsening Following Withdrawal of Etanercept or Methotrexate on Patient-Reported Outcomes in Patients With Rheumatoid Arthritis: Results From the SEAM-RA Trial.

BACKGROUND/OBJECTIVE: The effect of treatment withdrawal on patient-reported outcomes (PROs) in patients with rheumatoid arthritis (RA) whose disease is in sustained remission has not been well described. This analysis aimed to compare PRO changes in patients with RA following medication withdrawal and disease worsening. METHODS: SEAM-RA (Study of Etanercept and Methotrexate in Combination or as Monotherapy in Subjects With Rheumatoid Arthritis) was a phase 3, multicenter, randomized withdrawal, double-blind controlled study in patients with RA taking methotrexate plus etanercept and in remission (Simple Disease Activity Index ≤3.3). Patient's Global Assessment of Disease Activity, Patient's Assessment of Joint Pain, Health Assessment Questionnaire-Disability Index, and 36-Item Short-Form Health Survey were evaluated for 48 weeks following methotrexate or etanercept withdrawal. Treatment differences for patients with versus without disease worsening were evaluated using a 2-sample t test for continuous end points and log-rank test for time-to-event end points. RESULTS: Of 253 patients, 121 experienced disease worsening and 132 did not. All PRO scores were similar to those of a general population at baseline and deteriorated over time across the study population. The PtGA and Patient's Assessment of Joint Pain values deteriorated less in those on etanercept monotherapy compared with methotrexate monotherapy. More patients with versus without disease worsening experienced deterioration that was greater than the minimal clinically important difference (MCID) for all PROs tested. In patients with disease worsening, PtGA deterioration more than the MCID preceded Simple Disease Activity Index disease worsening. CONCLUSIONS: Etanercept monotherapy showed benefit over methotrexate in maintaining PRO scores. Patients with disease worsening experienced a more rapid worsening of PtGA beyond the MCID versus patients without disease worsening.Categories: autoinflammatory disease, biological therapy, DMARDs, rheumatoid arthritis.

Persistence on biologic DMARD monotherapy after achieving rheumatoid arthritis disease control on combination therapy: retrospective analysis of corrona registry data.

Biological disease-modifying antirheumatic drugs (bDMARDs) monotherapy may enhance adherence and decrease adverse events compared to combination therapy with conventional synthetic DMARDs (csDMARDs); however, persistence with bDMARD monotherapy has not been extensively studied. We explore persistence of etanercept monotherapy and monotherapy with other tumor necrosis factor inhibitors (TNFis) among patients first achieving remission/low disease activity (LDA) while on combination therapy with csDMARDs and a TNFi. Using Corrona registry data, the percentage of patients persistent with the index TNFi (etanercept versus other TNFis) over 6 and 12 months was determined. Factors influencing persistence and treatment patterns at 6 and 12 months were examined. Among 617 eligible patients, 56% of 182 patients on etanercept and 45% of 435 patients on other TNFis persisted with monotherapy at 6 months, 46% and 33%, respectively, at 12 months. Across first-line and subsequent biologic DMARDs, etanercept persistence was greater than other TNFi persistence by 10.8% (95% CI 2.1%, 19.6%) at 6 months and 11.4% (95% CI 0.9%, 21.9%) at 12 months. Patients on other TNFis were more likely to require reintroduction of csDMARD after 6 months (45% versus 35% for etanercept). Remission was the key predictor of persistence for both etanercept and other TNFi monotherapies. This retrospective, cohort study of registry data reflecting real-world practice indicates patients who achieve remission/LDA with combination csDMARD and TNFi therapy may successfully transition to TNFi monotherapy. Patients on etanercept monotherapy experienced greater persistence and less frequent reintroduction of a csDMARD than was observed for patients on other TNFi monotherapies.

Effect of IL-17 receptor A blockade with brodalumab in inflammatory diseases.

IL-17 cytokines are expressed by a variety of cells and mediate host defence against extracellular pathogens. IL-17 is upregulated at sites of inflammation and can synergize with other cytokines, such as TNF-α, to amplify the inflammatory response. Activation of these signalling pathways has been hypothesized to contribute to the underlying pathogenesis of several inflammatory diseases, including psoriasis, RA, PsA and asthma. Thus the IL-17 signalling pathway is an attractive target for the development of therapeutic agents to modulate aberrant inflammatory responses. This review of the clinical development of therapeutic agents that target IL-17 signalling pathways in inflammatory diseases focuses on brodalumab, a human anti-IL-17 receptor A mAb. The cumulative findings of early clinical studies with anti-IL-17 agents, including brodalumab, secukinumab and ixekizumab, provide strong evidence for the role of IL-17 signalling in the pathophysiology of certain inflammatory diseases and support the potential use of these agents in treating these diseases.

Long-term safety and efficacy of etanercept in children and adolescents with plaque psoriasis.

BACKGROUND: There are no systemic therapies approved in the United States to treat pediatric psoriasis. OBJECTIVE: We sought to evaluate long-term safety and efficacy of etanercept in children and adolescents with moderate to severe plaque psoriasis. METHODS: This 5-year, open-label extension study enrolled patients aged 4 to 17 years who had participated in a 48-week parent study. End points included occurrence of adverse events (AEs) and serious AEs including infections, and rates of 75% and 90% improvement in Psoriasis Area and Severity Index score and clear/almost clear on static physician global assessment. RESULTS: Of 182 patients enrolled, 181 received etanercept and 69 completed 264 weeks. Through week 264, 161 (89.0%) patients reported an AE, most commonly upper respiratory tract infection (37.6%), nasopharyngitis (26.0%), and headache (21.5%). Seven patients reported 8 serious AEs; only 1 (cellulitis) was considered treatment-related. No cases of opportunistic infections or malignancy were reported. Rates of 75% improvement in Psoriasis Area and Severity Index score (∼ 60%-70%) and 90% improvement in Psoriasis Area and Severity Index score (∼ 30%-40%) and static physician global assessment status clear/almost clear (∼ 40%-50%) were maintained through week 264. LIMITATIONS: The number of patients remaining on study at week 264 was small. CONCLUSION: Etanercept in pediatric patients was generally well tolerated and efficacy was maintained in those who remained in the study for up to 264 weeks.

Clinical meaningfulness of complete skin clearance in psoriasis.

BACKGROUND: New psoriasis therapies have increased the ability to achieve skin clearance. However, insufficient evidence exists on the impact of total skin clearance from the patient perspective. OBJECTIVE: We sought to determine if complete skin clearance is clinically meaningful compared with treatment responses without clearance. METHODS: Pooled data from 3 phase-III trials were used to compare results for patients with complete skin clearance (Psoriasis Area and Severity Index [PASI] 100 or static Physician Global Assessment score 0) with patients without complete skin clearance (PASI 75 to <100 or static Physician Global Assessment score 1) based on Psoriasis Symptom Inventory and Dermatology Life Quality Index. RESULTS: Percentages of patients with Psoriasis Symptom Inventory score 0 were 45% for those achieving PASI 100 and 8% for PASI 75 to <100 (P < .001). Respective percentages with Dermatology Life Quality Index score 0/1 were 80% and 55% (P < .001). PASI 100 resulted in incremental improvement over PASI 90 to <100 (incremental differences of 28% for Psoriasis Symptom Inventory score 0 and 18% for Dermatology Life Quality Index score 0). Similar results were observed for static Physician Global Assessment scores 0 versus 1. CONCLUSIONS: Complete skin clearance represents a clinically meaningful end point and outcome for patients, reflected in experiences of no psoriasis symptoms and no impairment on health-related quality of life.

Efficacy and safety of brodalumab in subpopulations of patients with difficult-to-treat moderate-to-severe plaque psoriasis.

BACKGROUND: Novel therapies are needed for difficult-to-treat populations of patients with psoriasis. OBJECTIVE: We sought to assess the efficacy and safety of the interleukin-17 Receptor A inhibitor brodalumab in patients with psoriasis with or without a self-reported history of psoriatic arthritis (PsA) and with or without a history of biologic use. METHODS: Subset analyses of a phase II, randomized, double-blind, placebo-controlled study of brodalumab in patients with moderate-to-severe plaque psoriasis were performed. Improvement from baseline in Psoriasis Area and Severity Index score of 75%, 90%, and 100% at week 12; static Physician Global Assessment (0/1) score; Dermatology Life Quality Index response; and Psoriasis Symptom Inventory response were evaluated within subgroups. RESULTS: Efficacy and quality-of-life measures were generally similar between subgroups of patients with or without a history of PsA and with or without a history of biologic use across brodalumab doses and were significantly higher among patients who received brodalumab 140 mg every 2 weeks or 210 mg every 2 weeks versus placebo. LIMITATIONS: Differences between subgroups were not compared statistically, PsA was self-reported, only skin involvement/symptoms were reported, and reasons for discontinuation of prior biologic were not captured. CONCLUSION: Brodalumab is efficacious in patients with psoriasis with or without a history of PsA or biologic use.

Safety and efficacy of brodalumab for psoriasis after 120 weeks of treatment.

BACKGROUND: Brodalumab (anti-interleukin-17-receptor antibody) was effective in treating moderate to severe psoriasis in a 12-week, dose-ranging, placebo-controlled trial. OBJECTIVE: We sought to evaluate efficacy and safety of long-term brodalumab treatment. METHODS: In this interim analysis at week 120 of an open-label extension study, patients received brodalumab 210 mg every 2 weeks. Protocol amendments reduced the dose (140 mg) in patients weighing 100 kg or less and subsequently increased the dose (210 mg) in patients with inadequate responses. Efficacy was measured by static physician global assessment and 75% or greater, 90% or greater, or 100% improvement in Psoriasis Area and Severity Index score (PASI-75, PASI-90, and PASI-100, respectively). RESULTS: Of 181 patients, 144 completed week 120. Static physician global assessment scores of clear/almost clear and clear were achieved by 90% and 63% of patients, respectively, at week 12 and by 72% and 51% at week 120. The PASI-75, PASI-90, and PASI-100 response rates at week 12 (95%/85%/63%) were sustained through week 120 (86%/70%/51%). Most commonly reported adverse events were nasopharyngitis (26.5%), upper respiratory tract infection (19.9%), arthralgia (16.0%), and back pain (11.0%). Four patients had grade-2 absolute neutrophil count. LIMITATIONS: There was no control group in this open-label extension. CONCLUSION: Brodalumab demonstrated sustained clinical response and an acceptable safety profile through 120 weeks in patients with moderate to severe psoriasis.

Treatment persistence and switching patterns of ABP 501 in European patients with inflammatory bowel disease.

Background: Approval of the adalimumab (ADA) biosimilar ABP 501 for inflammatory bowel disease (IBD) indications was based on the principle of extrapolation, without indication-specific clinical trial data. Objectives: To evaluate the real-world treatment patterns of ABP 501 in patients with IBD. Design: Retrospective analysis of pharmacy claims data from Germany and France. Methods: Continuously insured adult IBD patients who initiated ABP 501 between October 2018 and March 2020 were included. Treatment persistence, adherence, and post-ABP 501 switching patterns were evaluated for two mutually exclusive groups: ADA-naïve patients (i.e. no baseline use of ADA products) and ADA-experienced patients (i.e. previously treated with ADA products). Results: A total of 3362 German patients and 733 French patients were included, with 54.4% and 65.3% being ADA-naïve patients, respectively. Median persistence (95% CI) on ABP 501 was 10.9 months (9.8-11.6) in ADA-naïve patients and 14.2 months (12.7-15.2) in ADA-experienced patients in Germany; for the French cohort, ADA-naïve and -experienced patients had median persistence of 12.8 months (10.2-14.7) and 11.5 months (8.8-14.4), respectively. During the first 12 months of ABP 501 initiation, 53.7% of German patients and 51.0% of French patients were adherent to the therapy. About 20% of patients in both countries switched from ABP 501 to another targeted therapy. In the German cohort, ADA-naïve patients most frequently switched to non-tumor necrosis factor inhibitor biologics, but ADA-experienced patients most commonly switched to reference product (RP); in the French cohort, patients most often switched to RP regardless of prior exposure to ADA products. Conclusion: About 50% of patients persisted on and were adherent to ABP 501 therapy during the first 12 months after treatment initiation in two large European countries. Post-ABP 501, switching patterns varied between countries, indicating diversified treatment practices warranting further research on reason(s) for switching and potential overall treatment outcomes.

Treatment Persistence and Switching Patterns of Adalimumab Biosimilar ABP 501 in European Patients with Rheumatologic Diseases.

INTRODUCTION: ABP 501 was an adalimumab (ADA) biosimilar approved for treating immune-mediated inflammatory diseases (IMIDs) including rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS). In this retrospective study, we aimed to examine the treatment patterns of ABP 501 among patients with these IMIDs using German and French pharmacy claims databases. METHODS: Patients with RA, PsA, or AS who initiated ABP 501 between October 2018 and March 2020 and were observed continuously for ≥ 365 days both before and after ABP 501 initiation were included. Descriptive analyses of persistence and switch after ABP 501 discontinuation were conducted and reported for each disease cohort by prior use of ADA products (patients naïve to ADA or patients experienced with ADA). RESULTS: Median (95% confidence interval) persistence on ABP 501 was 9.4 (8.6-10.3), 10.2 (9.0-11.7), and 12.1 (11.0-13.1) months in German patients, and 11.7 (9.9-13.3), 7.1 (5.8-8.4), and 10.8 (9.6-11.9) months in French patients for RA, PsA, and AS, respectively. For patients who switched from ABP 501 to another targeted therapy during the first 12 months of follow-up, switching patterns varied between patients naïve to ADA and patients experienced with ADA in both Germany and France, with patients naïve to ADA switching most frequently to other targeted therapies including non-ADA tumor necrosis factor inhibitor (TNFi), non-TNFi biologic, or Janus Kinase inhibitor (JAKi) and patients experienced with ADA switching most frequently back to ADA reference product (RP). CONCLUSIONS: Across three rheumatologic diseases, about half of patients persisted on ABP 501 at the end of 12 months after treatment initiation in both Germany and France. Patients experienced with ADA were more likely to switch back to ADA RP, regardless of indication and country, suggesting a possible nocebo effect. Future studies are warranted to understand reasons of discontinuation and switching.

OX40 in the Pathogenesis of Atopic Dermatitis-A New Therapeutic Target.

Atopic dermatitis (AD) is a chronic, heterogeneous, inflammatory disease characterized by skin lesions, pruritus, and pain. Patients with moderate-to-severe AD experience chronic symptoms, intensified by unpredictable flares, and often have comorbidities and secondary complications, which can result in significant clinical burden that impacts the patient's overall quality of life. The complex interplay of immune dysregulation and skin barrier disruption drives AD pathogenesis, of which T-cell-dependent inflammation plays a critical role in patients with AD. Despite new targeted therapies, many patients with moderate-to-severe AD fail to achieve or sustain their individual treatment goals and/or may not be suitable for or tolerate these therapies. There remains a need for a novel, efficacious, well-tolerated therapeutic option that can deliver durable benefits across a heterogeneous AD patient population. Expression of OX40 [tumor necrosis factor receptor superfamily, member 4 (TNFRSF4)], a prominent T-cell co-stimulatory molecule, and its ligand [OX40L; tumor necrosis factor superfamily, member 4 (TNFSF4)] is increased in AD. As the OX40 pathway is critical for expansion, differentiation, and survival of effector and memory T cells, its targeting might be a promising therapeutic approach to provide sustained inhibition of pathogenic T cells and associated inflammation and broad disease control. Antibodies against OX40 [rocatinlimab (AMG 451/KHK4083) and telazorlimab (GBR 830)] or OX40L [amlitelimab (KY1005)] have shown promising results in early-phase clinical studies of moderate-to-severe AD, highlighting the importance of OX40 signaling as a new therapeutic target in AD.

A randomized study to evaluate the efficacy and safety of adding topical therapy to etanercept in patients with moderate to severe plaque psoriasis.

BACKGROUND: Few clinical trials have evaluated the combination of topical corticosteroids plus systemic therapies for psoriasis. OBJECTIVE: We sought to evaluate efficacy and safety of etanercept plus topical clobetasol propionate (CP) foam versus etanercept monotherapy for treatment of moderate to severe plaque psoriasis. METHODS: Adults with Psoriasis Area and Severity Index (PASI) score greater than or equal to 10 and psoriasis-affected body surface area greater than or equal to 10% were randomized to etanercept with CP as needed to clear (2 up-to-2-week courses, weeks 11-12 and 23-24) or etanercept alone (each arm at 50 mg twice weekly for 12 weeks followed by 50 mg once weekly for 12 weeks). RESULTS: A total of 592 patients enrolled (295 etanercept + CP arm; 297 etanercept arm). At week 12, significant differences were observed for response of 75% improvement in PASI score (primary end point, 65.2% vs 48.3% in the etanercept + CP vs etanercept arms, respectively; P < .001), response of 90% improvement in PASI score (29.7% vs 19.4%; P = .009), percentage PASI score improvement (76.5% vs 68.2%; P < .001), static physician global assessment of clear/almost clear (63.1% vs 47.3%; P < .001), and patient satisfaction with treatment (P = .006). Response of 75% improvement in PASI score and static physician global assessment of clear/almost clear were not significantly different between arms at week 24. Patient satisfaction with treatment (P = .001) and percentage improvement in PASI score (P = .031) were also greater in the etanercept + CP arm compared with etanercept only at week 24. Comparable numbers of adverse events occurred in each arm. LIMITATIONS: No placebo for CP foam was provided in the etanercept arm. CONCLUSIONS: Addition of CP to etanercept yielded increased efficacy compared with etanercept alone at week 12 without an increase in treatment-related adverse events.

Factors Associated With Maintenance of Remission Following Change From Combination Therapy to Monotherapy in Patients With Rheumatoid Arthritis.

OBJECTIVE: Some patients with rheumatoid arthritis (RA) who persist in remission may decide to stop their therapy. We evaluated baseline characteristics associated with remaining in remission or low disease activity (LDA) following medication withdrawal. METHODS: The Study of Etanercept and Methotrexate in Combination or as Monotherapy in Subjects With Rheumatoid Arthritis (SEAM-RA) was a phase III, multicenter, randomized withdrawal, double-blind, controlled study in patients with RA on methotrexate (MTX) + etanercept (ETN). If remission (Simplified Disease Activity Index [SDAI] ≤ 3.3) was sustained through a 24-week run-in period, patients then entered a 48-week double-blind period and were randomized 2:2:1 to receive MTX monotherapy, ETN monotherapy, or continue combination therapy. Multivariate logistic regression analysis was performed to identify baseline factors associated with remission or LDA at the end of both periods. RESULTS: Of 371 patients enrolled, 253 entered the double-blind period. After adjusting for other factors, covariates associated with achieving SDAI remission at the end of the run-in period included younger age, longer duration of MTX treatment, and less severe clinical disease variables. Covariates associated with maintaining remission/LDA at the end of the 48-week double-blind period included lower patient global assessment of disease activity (PtGA), lower C-reactive protein, rheumatoid factor (RF) negativity, longer RA duration in the MTX arm, shorter duration of ETN treatment, and lower magnesium. CONCLUSION: These findings indicate patients with overall lower disease activity are more likely to remain in SDAI remission/LDA after switching from combination therapy to monotherapy. RF-negative status and lower PtGA scores were strongly associated with increased likelihood of remaining in remission/LDA with MTX or ETN monotherapy. (SEAM-RA; ClinicalTrials.gov: NCT02373813).

Etanercept or Methotrexate Withdrawal in Rheumatoid Arthritis Patients in Sustained Remission.

OBJECTIVE: Patients with rheumatoid arthritis (RA) in whom remission is achieved following combination therapy with methotrexate plus etanercept face an ongoing medication burden. This study was undertaken to investigate whether sustained remission achieved on combination therapy can be maintained with either methotrexate or etanercept monotherapy, as assessed following discontinuation of one or the other medication from the combination. METHODS: Of the 371 adult patients with RA who received combination therapy with methotrexate plus etanercept, remission (defined as a Simplified Disease Activity Index [SDAI] score of ≤3.3) was sustained in 253 patients through a 24-week open-label period. These 253 patients then entered a 48-week, double-blind period and were randomized to receive either 1) methotrexate monotherapy (n = 101), 2) etanercept monotherapy (n = 101), or 3) methotrexate plus etanercept combination therapy (n = 51). Patients who subsequently experienced disease-worsening received rescue therapy with the combination regimen at the same dosages as used in the initial run-in period. The primary end point was the proportion of patients in whom SDAI-defined remission was maintained without disease-worsening at week 48 in the etanercept monotherapy group as compared to the methotrexate monotherapy group. Secondary end points included time to disease-worsening, and the proportion of patients in whom SDAI-defined remission was recaptured after initiation of rescue therapy. RESULTS: Baseline demographic and clinical characteristics of the RA patients were similar across the treatment groups. At week 48, SDAI-defined remission was maintained in significantly more patients in the etanercept monotherapy group than in the methotrexate monotherapy group (49.5% versus 28.7%; P = 0.004). Moreover, as a secondary end point, sustained SDAI-defined remission was achieved in significantly more patients who received combination therapy than in those who received methotrexate monotherapy (52.9% versus 28.7%; P = 0.006). Time to disease-worsening was shorter in those who received methotrexate monotherapy than in those who received etanercept monotherapy or those who received combination therapy (each P < 0.001 versus methotrexate monotherapy). Among the patients who received rescue therapy, SDAI-defined remission was recaptured in 70-80% in each treatment group. No new safety signals were reported. CONCLUSION: The efficacy of etanercept monotherapy was superior to that of methotrexate monotherapy and similar to that of combination therapy in maintaining remission in patients with RA. SDAI-defined remission was recaptured in most of the patients who were given rescue therapy. These data could inform decision-making when withdrawal of therapy is being considered to reduce treatment burden in patients with well-controlled RA.

Long-term etanercept in pediatric patients with plaque psoriasis.

BACKGROUND: No systemic therapies are approved by the US Food and Drug Administration for the treatment of psoriasis in children and adolescents. OBJECTIVE: We sought to evaluate the long-term safety and efficacy of etanercept in pediatric patients (aged 4-17 years) with moderate to severe plaque psoriasis. METHODS: Patients who completed or received substantial treatment benefit in a 48-week, randomized, double-blind, placebo-controlled study (N = 211) evaluating the efficacy and safety of once-weekly etanercept (0.8 mg/kg) were enrolled in this 264-week open-label extension study. The primary end point was the occurrence of adverse events. Secondary end points included Psoriasis Area and Severity Index 50%, 75%, and 90% responses compared with baseline; static Physician Global Assessment; and clear and clear/almost clear static Physician Global Assessment status. Results from a 96-week interim analysis are presented. RESULTS: Of 182 enrolled patients, 181 received treatment and 140 (76.9%) completed week 96. A total of 145 patients (80.1%) reported adverse events; 5 serious adverse events occurred in 3 patients, none of which were treatment related. Observed Psoriasis Area and Severity Index 50% (89%), 75% (61%), and 90% (30%) responses compared with baseline at week 96 were similar to those observed in the double-blind trial. The static Physician Global Assessment was maintained through week 96, when 47% of patients achieved clear/almost clear status. LIMITATIONS: This is an interim analysis from an open-label study. CONCLUSION: Extended treatment with etanercept in pediatric patients with moderate to severe plaque psoriasis was generally well tolerated, and efficacy was maintained through 96 weeks.

Maintenance of Sustained Low Disease Activity or Remission in Patients With Rheumatoid Arthritis Treated With Etanercept Monotherapy: Results from the Corrona Registry.

OBJECTIVE: The purpose of this study was to evaluate maintenance of remission/low disease activity (LDA) in patients with rheumatoid arthritis (RA) who achieved remission/LDA with etanercept (ETN) plus a conventional synthetic disease-modifying antirheumatic drug (csDMARD) and to compare patients who discontinued csDMARD to receive ETN monotherapy (Mono) with those remaining on combination therapy (Combo). METHODS: Patients from the Corrona RA registry between October 1, 2001, and August 31, 2017, were eligible. The index date for the Mono cohort was the csDMARD discontinuation date; the index visit for the Combo cohort was estimated from time between ETN initiation and csDMARD discontinuation in the Mono cohort. The main outcome calculated was maintenance of remission/LDA. Patients were censored if they switched to or added a biologic DMARD, discontinued ETN, when a csDMARD was reintroduced (Mono), or if methotrexate increased more than 5 mg/d (Combo). Trimming was used to balance demographic and clinical characteristics between groups. Cox regression models were adjusted for the remaining differences across groups. RESULTS: We identified 182 Mono and 403 Combo patients; 120 Mono and 207 Combo patients remained after trimming. Most patients (approximately 80%) were biologic medication-naive before initiating ETN. At 24 months postindex, modeled percentages of patients remaining in remission/LDA were 75% for Mono and 86% for Combo (overall adjusted P = 0.057). More patients were censored for therapy change in Mono than in Combo groups (37% versus 5%), largely due to reintroduction of csDMARDs in the Mono group. CONCLUSION: Many patients with RA who achieved remission/LDA on combination therapy maintained remission/LDA with ETN monotherapy for 2 years after csDMARD discontinuation. ETN monotherapy may be a viable option for patients who discontinue csDMARDs after achieving LDA/remission.

Randomized, double-blind, placebo-controlled evaluation of the efficacy of oral psoralen plus ultraviolet A for the treatment of plaque-type psoriasis using the Psoriasis Area Severity Index score (improvement of 75% or greater) at 12 weeks.

BACKGROUND: Psoralen plus ultraviolet A (PUVA) for the treatment of psoriasis has never been evaluated using the Psoriasis Area Severity Index (PASI) in a randomized, double-blind, placebo-controlled trial. The lack of such data limits our capacity to estimate PUVA's efficacy relative to other treatment options that are available today. OBJECTIVES: The purpose of this study was to evaluate the efficacy of PUVA therapy for patients with plaque-type psoriasis. METHODS: This study involved 40 patients with psoriasis; 30 received PUVA and 10 received UVA with placebo. PASI scores were assessed at baseline and every 4 weeks thereafter for 12 weeks. RESULTS: By nonresponder imputation, 60% (18 of 30) in the PUVA group achieved 75% or more improvement in PASI score after 12 weeks of treatment compared with 0% (0 of 10) in the UVA plus placebo group (P < .0001). Using intent to treat with last observation carried forward analysis, 63% (19 of 30) in the PUVA group achieved 75% or more improvement in PASI score compared with 0% (0 of 10) in the UVA plus placebo group (P < .0001). By per protocol analysis, 86% (18 of 21) in the PUVA group as compared with 0% (0 of 7) in the UVA plus placebo group reached 75% or more improvement in PASI score after 12 weeks (P < .0001). LIMITATIONS: The study was relatively small with only 40 patients enrolled and 28 patients who completed the protocol. Further studies that involve head-to-head comparison of PUVA with other treatment modalities are needed. Nonresponder imputation, last observation carried forward with intent to treat, and per protocol analyses each have separate advantages and limitations when determining clinical significance. CONCLUSIONS: This study supports the observation that PUVA is a highly efficacious treatment for chronic plaque psoriasis.

5% 5-Fluorouracil cream for treatment of verruca vulgaris in children.

Warts are a common pediatric skin disease. Most treatments show only modest benefit, and some are poorly tolerated because of pain. 5-fluorouracil interferes with deoxyribonucleic acid and ribonucleic acid synthesis, and is used to treat genital warts in adults. Efficacy, safety, and tolerability of topical 5% 5-fluorouracil for treatment of common warts were examined in an open-label pilot study with pediatric patients. Thirty-nine children who have at least two hand warts applied 5% 5-fluorouracil cream (Efudex, Valeant Pharmaceuticals International) once or twice daily, under occlusion for 6 weeks. Assessment of treatment response and side effects was performed at baseline, treatment completion, and 3- and 6-month follow-ups. Hematology measures, liver function tests, and medication blood levels were reassessed at treatment completion. Eighty-eight percent of treated warts improved after 6 weeks of treatment, and 41% of subjects had complete resolution of at least one wart. Treatment response did not differ between once or twice daily applications. Tolerability and patient satisfaction were excellent. No subject had clinically significant blood levels of 5-fluorouracil. At 6 month follow-up, 87% of complete responders had no wart recurrence. Topical 5% 5-fluorouracil is a safe, effective, and well-tolerated treatment for warts in children.

Decreased Injection Site Pain Associated with Phosphate-Free Etanercept Formulation in Rheumatoid Arthritis or Psoriatic Arthritis Patients: A Randomized Controlled Trial.

INTRODUCTION: Etanercept, a tumor necrosis factor inhibitor, is used to treat rheumatoid arthritis (RA) and psoriatic arthritis (PsA), and is administered via subcutaneous injection. Injection site pain (ISP) associated with subcutaneous administration may affect compliance or hinder initiation of prescribed medications. To improve the patient experience, a new phosphate-free formulation of etanercept was evaluated for reduced ISP associated with administration. METHODS: This phase 3b, multicenter, randomized, double-blind, cross-over study compared the prior formulation of etanercept to a phosphate-free formulation. Etanercept-naïve adults with RA or PsA indicated for treatment with etanercept were eligible. Patients were randomized (1:1) to receive both etanercept formulations (50 mg) in one of two crossover sequences: prior formulation followed by phosphate-free formulation (sequence AB) or phosphate-free formulation followed by prior formulation (sequence BA) at visits 1 week apart. Patients self-reported ISP using a fit-for-purpose 100-mm visual analog scale within 30 s after injection. Safety outcomes included incidence of treatment-emergent adverse events. Mixed-effects analysis of variance model was used to assess ISP, with treatment, study period, sequence, and disease indication as fixed-effect covariates and patient-within-sequence as random effect. RESULTS: A total of 111 patients enrolled (56 sequence AB; 55 sequence BA). Mean ISP score for prior formulation was 23.1 mm and for phosphate-free formulation was 19.1 mm (mean difference - 4 mm; 95% confidence interval: - 8.0, 0.0; P = 0.048). Patients with the highest ISP scores from the prior formulation (by quartile cut points) had the largest reduction in pain with phosphate-free formulation. Injection site reactions were few in number and similar between formulations; no new safety signals were observed. CONCLUSIONS: The new phosphate-free formulation of etanercept had statistically significantly lower mean pain scores than the prior formulation, with largest pain reductions observed among patients who reported highest pain with the prior formulation. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02986139. FUNDING: Amgen Inc, Thousand Oaks, CA USA.

Pharmacokinetics, Immunogenicity, and Efficacy of Etanercept in Pediatric Patients With Moderate to Severe Plaque Psoriasis.

Etanercept has been recently approved in the United States for the treatment of moderate to severe plaque psoriasis in patients aged 4-17 years. The objective of this study was to characterize etanercept pharmacokinetics, immunogenicity, and efficacy in pediatric patients. Data from a phase 3 study and open-label extension study were analyzed. Etanercept serum concentrations in pediatric patients receiving etanercept 0.8 mg/kg (maximum, 50 mg) weekly were compared with adult psoriasis patients and pediatric patients with juvenile idiopathic arthritis (JIA) who received etanercept 0.4 mg/kg twice weekly. The developments of antietanercept antibodies and efficacy based on the Psoriasis Area and Severity Index were evaluated. Steady-state trough etanercept concentrations were similar across visits from weeks 12-48, between patients aged 4-11 and 12-17 years, between pediatric and adult psoriasis patients, and between pediatric patients with psoriasis or JIA. Etanercept serum concentrations and safety profiles were similar in patients with (15.9%) and without antietanercept antibodies. Dosing used in the study provided similar exposures and efficacy across ranges of weight and body mass index. Pharmacokinetic, immunogenicity, and efficacy data support 0.8 mg/kg (maximum, 50 mg) weekly dosing of etanercept in patients aged 4-17 years.