Alex Mutebi

Improvement in Psoriasis Signs and Symptoms Assessed by the Psoriasis Symptom Inventory with Brodalumab Treatment in Patients with Psoriatic Arthritis

Objective. To evaluate the effect of brodalumab on psoriasis signs and symptoms assessed by the Psoriasis Symptom Inventory (PSI) in patients with psoriatic arthritis (PsA). Methods. This prespecified analysis of a phase II study (NCT01516957) evaluated patients with active PsA and psoriasis-affected body surface area ≥ 3%, randomized to brodalumab (140 or 280 mg) or placebo every 2 weeks (Q2W) for 12 weeks with loading dose at Week 1. At Week 12, patients entering an open-label extension received brodalumab 280 mg Q2W. The PSI measures 8 psoriasis signs and symptoms: itch, redness, scaling, burning, stinging, cracking, flaking, and pain. PSI response is defined as total PSI ≤ 8 (range 0–32), each item ≤ 1 (range 0–4). PSI scores were assessed at weeks 12 and 24. Results. There were 107 eligible patients. At Week 12, mean improvement in PSI scores was 7.8, 11.2, and 1.5 in brodalumab 140 mg, 280 mg, and placebo groups, respectively; by Week 24, improvement was 10.2, 12.4, and 11.7. At Week 12, 75.0%, 81.8%, and 16.7% of patients receiving brodalumab 140 mg, 280 mg, and placebo, respectively, achieved PSI response; improvement was sustained through Week 24, when 83.9% of prior placebo recipients achieved response. At Week 12, 25.0%, 36.4%, and 2.8% of patients receiving brodalumab 140 mg, 280 mg, and placebo, respectively, achieved PSI 0. Percentages improved through Week 24: 40.0% brodalumab 140 mg, 42.9% brodalumab 280 mg, and 48.4% placebo. Conclusion. Significantly more brodalumab-treated patients with PsA achieved patient-reported improvements in psoriasis signs and symptoms than did those receiving placebo. Improvements were comparable between brodalumab groups.

Cost-effectiveness of sequenced treatment of rheumatoid arthritis with targeted immune modulators

Abstract Aims: To determine the cost-effectiveness of treatment sequences of biologic disease-modifying anti-rheumatic drugs or Janus kinase/STAT pathway inhibitors (collectively referred to as bDMARDs) vs conventional DMARDs (cDMARDs) from the US societal perspective for treatment of patients with moderately to severely active rheumatoid arthritis (RA) with inadequate responses to cDMARDs. Materials and methods: An individual patient simulation model was developed that assesses the impact of treatments on disease based on clinical trial data and real-world evidence. Treatment strategies included sequences starting with etanercept, adalimumab, certolizumab, or abatacept. Each of these treatment strategies was compared with cDMARDs. Incremental cost, incremental quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs) were calculated for each treatment sequence relative to cDMARDs. The cost-effectiveness of each strategy was determined using a US willingness-to-pay (WTP) threshold of

Reliability and Validity of the Psoriasis Symptom Inventory in Patients With Psoriatic Arthritis.

150,000/QALY. Results: For the base-case scenario, bDMARD treatment sequences were associated with greater treatment benefit (i.e. more QALYs), lower lost productivity costs, and greater treatment-related costs than cDMARDs. The expected ICERs for bDMARD sequences ranged from ∼

Measurement Properties of the Psoriasis Symptom Inventory Electronic Daily Diary in Patients with Moderate to Severe Plaque Psoriasis.

126,000 to

Rebound in Measures of Disease Activity and Symptoms in Corrona Registry Patients with Psoriatic Arthritis Who Discontinue Tumor Necrosis Factor Inhibitor Therapy after Achieving Low Disease Activity

140,000 per QALY gained, which is below the US-specific WTP. Alternative scenarios examining the effects of homogeneous patients, dose increases, increased costs of hospitalization for severely physically impaired patients, and a lower baseline Health Assessment Questionnaire (HAQ) Disability Index score resulted in similar ICERs. Conclusions: bDMARD treatment sequences are cost-effective from a US societal perspective.

THU0423 Time To Rebound in Joint Symptoms Following Discontinuation of TNFI Therapy after Achieving Low Disease Activity or Remission in Psoriatic Arthritis Patients Enrolled in The US Corrona Registry

To evaluate the measurement properties of the Psoriasis Symptom Inventory (PSI) in psoriatic arthritis (PsA).

AB0755 Reliability and Construct Validity of the Psoriasis Symptom Inventory in Subjects with Psoriatic Arthritis

OBJECTIVES The Psoriasis Symptom Inventory (PSI) is a patient-reported outcome instrument that measures the severity of psoriasis signs and symptoms. This study evaluated measurement properties of the PSI in patients with moderate to severe plaque psoriasis. METHODS This secondary analysis used pooled data from a phase 3 brodalumab clinical trial (AMAGINE-1). Outcome measures included the PSI, Psoriasis Area and Severity Index (PASI), static Physicians Global Assessment (sPGA), psoriasis-affected body surface area, 36-item Short-Form Health Survey version 2, and the Dermatology Life Quality Index (DLQI). The PSI was evaluated for dimensionality, item performance, reliability (internal consistency and test-retest), construct validity, ability to detect change, and agreement between PSI response and response measures based on the PASI, sPGA, and DLQI. RESULTS Results supported unidimensionality, good item fit, ordered responses, and PSI scoring. The PSI demonstrated reliability: baseline Cronbachs alpha ≥ 0.92 and intraclass correlation coefficients ≥ 0.95. Correlations between PSI total score and DLQI item 1 (r = 0.86), DLQI symptoms and feelings (r = 0.87), and 36-item Short-Form Health Survey version 2 bodily pain (r = -0.61) supported convergent validity. PSI scores differed significantly (P < 0.001) among severity groups based on the PASI (< 12/≥ 12), sPGA (0-1/2-3/4-5), body surface area (< 5%/5%-10%/> 10%), and DLQI (≤ 5/> 5) at weeks 8 and 12. At week 12, the PSI detected significant changes in severity based on PASI responses (< 50/50- < 75/≥ 75) and sPGA (0-1/≥ 2), and showed good agreement (k ≥ 0.66) between PSI response and PASI, sPGA, and DLQI responses. CONCLUSION The PSI demonstrated excellent validity, reliability, and ability to detect change in the severity of psoriasis signs and symptoms.

Impact of prior biologic use on persistence of treatment in patients with psoriatic arthritis enrolled in the US Corrona registry

Objective. Rebound may occur in patients with psoriatic arthritis (PsA) who discontinue TNF inhibitor (TNFi) therapy in low disease activity (LDA). Methods. Using physician and patient reports, we quantified rebound following TNFi discontinuation [defined as Clinical Disease Activity Index (CDAI) score > 10 or TNFi restart] and time to rebound in adults with PsA in LDA (CDAI score ≤ 10) at TNFi discontinuation. Results. Rebound occurred in 73% (69/94) of patients soon after discontinuation (median time to rebound 8.0 mos, 95% CI 6.0–12.0). Conclusion. Rebound occurred frequently in patients with PsA after TNFi discontinuation. TNFi discontinuation after achieving LDA should be carefully considered.

Factors Associated With A History Of Failure And Switching Migraine Prophylaxis Treatment: An Analysis Of Clinical Practice Data From The United States, Germany, France, And Japan

Background The treatment goal for patients (pts) with psoriatic arthritis (PsA) is to suppress disease activity. Little is known about clinical outcomes in pts who stop TNFi therapy after achieving low disease activity (LDA) during routine care. Objectives We evaluated time to rebound (i.e., increase in joint symptoms after therapy discontinuation) in pts with PsA who achieved LDA prior to stopping TNFi therapy as well as changes in measures of disease activity at the first visit following TNFi discontinuation. Methods In the Corrona registry, we identified pts with PsA who initiated a TNFi (adalimumab, etanercept, infliximab, golimumab), achieved LDA based on Clinical Disease Activity Index (CDAI) ≤10 on TNFi therapy, discontinued TNFi altogether while still in LDA (persistence on conventional disease modifying medication was allowed) and had at least 1 follow-up visit while off TNFi. Demographic and clinical characteristics were assessed at discontinuation date (index date). To assess time to rebound, pts were followed until earliest of the following events: rebound of symptoms (CDAI >10), initiation of another biologic/small molecule or last follow-up visit. Kaplan-Meier curves were generated for time to rebound (CDAI >10). To assess impact of TNFi discontinuation, change in disease activity measures including CDAI, modified Health Assessment Questionnaire (mHAQ), pt and physician global assessments, and pt pain were assessed between discontinuation and first post-index visit. Results There were 94 pts (57% female, 51% biologic-experienced at TNFi initiation) who met study criteria. At TNFi discontinuation, mean (standard deviation [SD]) age and disease duration were 52.6 (12.7) and 9.8 (7.4) years, respectively. Over time, 67 (73%) pts had a rebound in symptoms, with median time to rebound of 8 months (95% CI 6–12). At first post-index visit, there was a significant mean increase in all measures of disease activity except mHAQ (Table).Table 1. Disease activity measures at index (TNFi discontinuation), first post-index visit, and change during interval Disease activity measure Index: Follow-up visit: Mean change (SD) p-value Mean (SD) Mean (SD) CDAI 4.3 (3.1) 7.5 (7.7) −3.2 (6.9) <0.0001 mHAQ 0.24 (0.35) 0.27 (0.38) −0.03 (0.26) 0.328 Physician Global 9.9 (10) 14.7 (14.9) −4.8 (15.4) 0.003 Pt. Global 23.2 (21.4) 29.6 (25.6) −6.5 (23.7) 0.01 Pt. Pain 26.4 (24.9) 32.1 (26.7) −5.6 (20.7) 0.01 Conclusions Rebound of symptoms in PsA patients occurred frequently with the majority of patients having worsening of disease activity by the next visit after TNFi discontinuation. These results suggest careful consideration before stopping these agents after achievement of low disease activity. Acknowledgement This study is sponsored by Corrona, LLC. The Corrona RA registry has been supported through contracted subscriptions in the last two years by AbbVie, Amgen, BMS, Crescendo, Genentech, Horizon Pharma USA, Janssen, Eli Lilly, Novartis, Pfizer, and UCB. Disclosure of Interest L. Harrold Grant/research support from: Pfizer and Astra Zeneca, Consultant for: Genentech and Pfizer, Employee of: Corrona, LLC, B. Stolshek Shareholder of: Amgen, Inc., Employee of: Amgen, Inc., S. Rebello Employee of: Corrona, LLC, D. Collier Shareholder of: Amgen, Inc., Employee of: Amgen, Inc., A. Mutebi Employee of: Amgen, Inc., S. Wade Consultant for: Amgen, Inc., W. Malley Employee of: Corrona, LLC, Paid instructor for: Lamar University, J. Greenberg Shareholder of: Corrona, LLC, Consultant for: AstraZeneca, Celgene, Genentech, Janssen, Novartis and Pfizer, Employee of: Corrona, LLC, C. Etzel Consultant for: Merck, Employee of: Corrona, LLC

The Use Of Migraine Prophylaxis Treatment: Analysis Of Clinical Practice Data From The United States, Germany, France, And Japan

Background The Psoriasis Symptom Inventory (PSI) is an 8-item patient-reported outcome measure of psoriasis symptom severity. Data from a Phase 2 study of Brodalumab in subjects with plaque psoriasis demonstrated that the PSI has good reliability, validity, and ability to detect change.1 Psoriasis related symptoms are an important component of psoriatic arthritis (PsA). However, the measurement properties of the PSI have not been evaluated in the PsA population. Objectives To evaluate the reliability and construct validity of the PSI in subjects with PsA. Methods This was a secondary analysis of pooled data from treatment arms of a Phase 2 clinical trial (NCT01516957) evaluating the efficacy of Brodalumab, an anti-IL-17 R monoclonal antibody in subjects with PsA. Confirmatory factor analysis (CFA) and Rasch analysis were used to assess the dimensionality of the PSI. Item evaluation and internal consistency (Cronbachs α) were conducted on baseline PSI data. Test-retest reliability was assessed using intraclass correlation coefficients (ICC) between PSI scores at week 2 and week 4 in stable subjects (i.e., -1≤ change ≤1 on the subject global assessment of disease [SGA]). Construct validity was evaluated based on correlations between PSI scores and body surface area (BSA) affected by psoriasis, and selected domains of the SF-36. Known groups validity was explored based on BSA severity categories (<5%, 5-10%, >10%) using analysis of variance. Ability to detect change was explored using t-tests comparing mean PSI scores in subjects reporting ≥30% versus <30% improvement from baseline to week 12 on the SGA. Results The analysis sample included 154 subjects; 93.5% White, 63.0% females, mean (SD) age was 52.2 (11.47) years. Mean (SD) duration of PsA and BSA at baseline was 8.8 (7.84) years and 10.4% (15.61%) respectively. At baseline, 12% of subjects had no skin involvement and 63% had ≤5% skin involvement. Mean (SD) PSI total score at baseline was 12.2 (7.89). CFA and Rasch analysis supported unidimensionality. Rasch analysis also indicated good item fit and correctly ordered categories. The PSI had excellent internal consistency (α=0.95) and good test-retest reliability (ICC=0.70 for total scores and ranging from 0.67 to 0.81 for items). Convergent validity was supported by moderate correlations with BSA (r=0.50). Discriminant validity was supported by small correlations (r<-0.3) for SF-36 domains of mental health and role emotions. Known groups validity was supported by significantly lower mean PSI scores (p<0.001) between subjects with BSA<5% compared to those with BSA>10%). Mean change in PSI score was significantly greater (p<0.001) in subjects with ≥30% SGA improvement than subjects with <30% SGA improvement. Conclusions This study provides evidence that the PSI is unidimensional, with excellent internal consistency, good test-retest reliability, construct validity, and ability to detect change in subjects with PsA. Based on the findings, the PSI is a robust yet simple and practical measure of psoriasis-related symptoms for use in PsA clinical trials. References Revicki DA et al. Reliability and validity of the psoriasis symptom inventory in patients with moderate-to-severe psoriasis. J Dermatolog Treat. 2013:Epub 1-7. Disclosure of Interest P. Mease Grant/research support: Received Research grants from Abbvie, Amgen, BiogenIdec, BMS, Celgene, GlaxoSmithKline, Janssen, Lilly, Merck, Norvatis, Pfizer, UCB, Vertex., Consultant for: Received consulting fees from Abbvie, Amgen, BiogenIdec, BMS, Celgene, GlaxoSmithKline, Janssen, Lilly, Merck, Norvatis, Pfizer, UCB, Vertex., Speakers bureau: Received speaker honoraria from Abbvie, Amgen, BiogenIdec, BMS, Celgene, GlaxoSmithKline, Janssen, Lilly, Merck, Norvatis, Pfizer, UCB, Vertex., M. Genovese Grant/research support: Received research grants from Amgen Inc., A. Mutebi Shareholder of: Amgen Inc., Employee of: Amgen Inc., H. Wilson Consultant for: Received consulting fees from Amgen Inc., D. Revicki Consultant for: Received consulting fees from Amgen Inc., N. Erondu Shareholder of: Amgen Inc., Employee of: Amgen Inc., A. Nirula Shareholder of: Amgen Inc., Employee of: Amgen Inc., J. Feng Shareholder of: Amgen Inc., Employee of: Amgen Inc., H. Viswanathan Shareholder of: Amgen Inc., Employee of: Amgen Inc. DOI 10.1136/annrheumdis-2014-eular.3778