This 78-week (18-month) study conducted in 479 postmenopausal women with osteoporosis evaluated the efficacy, pharmacodynamics, pharmacokinetics, safety, and immunogenicity of candidate biosimilar CT-P41 relative to US reference denosumab. CT-P41 had equivalent efficacy and pharmacodynamics to US-denosumab, with similar pharmacokinetics and comparable safety and immunogenicity profiles. To demonstrate equivalence of candidate biosimilar CT-P41 and US reference denosumab (US-denosumab) in postmenopausal women with osteoporosis. This 78-week (18-month), double-blind, randomized, active-controlled Phase 3 study (NCT04757376) comprised two treatment periods (TPs). In TPI, patients (N = 479) were randomized 1:1 to 60 mg subcutaneous CT-P41 or US-denosumab. At Week 52, those who had received CT-P41 in TPI continued to do so. Those who had received US-denosumab were randomized (1:1) to continue treatment or switch to CT-P41 in TPII. The primary efficacy endpoint was percent change from baseline in lumbar spine bone mineral density at Week 52. Efficacy equivalence was concluded if associated 95

Background In PALACE psoriatic arthritis (PsA) studies, the Bath Ankylosing Spondylitis Disease Activity Index score (BASDAI) was used as an exploratory measure in a subset of patients (pts) considered by investigators to have axial involvement, although PsA spondylitis was not confirmed by imaging. Objectives Report the impact of apremilast 30 mg BID (APR) treatment on BASDAI over 156 wks using pooled PALACE 1–3 data of pts with active PsA despite prior conventional DMARDs and/or biologics. Methods APR treatment outcomes were evaluated in a subset of pts with baseline (BL) BASDAI ≥4 (“subset”) over 156 wks. Results BL BASDAI ≥4 was reported for 454/1493 (30%) pts. Mean PsA duration was similar between the subset and rest of the PALACE 1–3 population (n=1039); mean BL psoriasis body surface area (BSA) and percentage of pts with BSA ≥3% were slightly higher. The subset had higher mean BL values vs the rest of PALACE 1–3 pts for C-reactive protein (1.12 vs 0.93), pain VAS (63.6 vs 53.8 mm), pt9s global assessment of disease activity (62.2 vs 53.5 mm), and physician9s global assessment of disease activity (PhGA; 59.0 vs 53.0 mm) and markedly worse mean HAQ-DI (1.41 vs 1.08), SF-36v2 Physical Functioning (30.6 vs 35.8), and FACIT-F (25.7 vs 31.8) scores. Despite disease activity differences, BL concomitant oral DMARDs were similar in both groups: 1 DMARD in 61.0% (subset) vs 57.8% (rest of PALACE 1–3 pts); methotrexate was the most common DMARD. In the subset, 73.6% had been treated with only oral DMARDs prestudy (44.9% with only 1); 25.1% had prior biologic use. Mean BL BASDAI in the subset was 6.6 with APR and 6.4 with placebo (PBO). Mean BL BASDAI question 2 score, referring directly to spinal and hip pain, was 6.7. APR resulted in greater mean improvement in BASDAI vs PBO at Wk 16 (−1.53 vs −0.91; P=0.0173) and Wk 24 (Table). As early as Wk 16, a 19% mean decrease in the question 2 score was seen with APR vs an increase with PBO. Other disease measures significantly improved early in treatment, including HAQ-DI, fatigue, PhGA, and mPsARC (Table). Long-term improvement was seen across measures, with mean BASDAI reductions of 2.18 at Wk 52 and 2.19 at Wk 156 (Table) and question 2 reductions of 1.94 and 2.28, respectively; treatment resulted in a shift toward lower BASDAI across the subset, with a significant proportion reaching BASDAI <4. Conclusions In this post hoc analysis of pooled data, pts reporting BASDAI ≥4 at BL appear to experience greater disease burden, including disability, pain, and fatigue; effective treatment strategies may not have been available. APR treatment resulted in long-term improvements in BASDAI and other measures in pts with clinically suspected axial disease. Disclosure of Interest P. Mease Grant/research support from: Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Genentech, Janssen, Eli Lilly, Novartis, Pfizer, Roche, UCB, Consultant for: Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Genentech, Janssen, Eli Lilly, Novartis, Pfizer, Roche, UCB, Speakers bureau: Abbott, Amgen, Biogen Idec, BMS, Genentech, Janssen, Eli Lilly, Pfizer, UCB, H. Marzo-Ortega: None declared, A. Poder: None declared, F. Van den Bosch Consultant for: AbbVie, Celgene Corporation, Merck, Pfizer, UCB, Janssen, J. Wollenhaupt Grant/research support from: Abbott, BMS, MSD, Pfizer, UCB, Consultant for: Abbott, BMS, MSD, Pfizer, UCB, E. Lespessailles Grant/research support from: Amgen, Eli Lilly, Novartis, Servier, Speakers bureau: Amgen, Eli Lilly, Novartis, Servier, M. McIlraith Employee of: Celgene Corporation, L. Teng Employee of: Celgene Corporation, S. Hall Consultant for: Boehringer Ingelheim, MSD, Roche, Schering-Plough, Servier, Wyeth, Paid instructor for: Amgen, AstraZeneca, Boehringer Ingelheim, Centocor, GSK, MSD, Pfizer, Sanofi Aventis, Sanofi Pasteur, Schering-Plough, Serono, Wyeth, Speakers bureau: Boehringer Ingelheim, GSK, MSD, Pfizer, Roche, Sanofi Aventis, Schering-Plough, Wyeth

Background In the PALACE psoriatic arthritis (PsA) trials, the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score was obtained as an exploratory measure in a subset of patients (pts) considered by investigators to have axial involvement, although PsA spondylitis was not confirmed by more objective measures such as MRI. Objectives Assess the impact of apremilast 30 mg BID (APR) on BASDAI over 52 wks using PALACE 1 (NCT01172938), 2 (NCT01212757), and 3 (NCT01212770) pooled data of pts with active PsA despite prior conventional DMARDs and/or biologics. Methods APR was evaluated in a subset of pts with baseline (BL) BASDAI ≥4 (“subset”) over 16, 24, and 52 wks. Results BL BASDAI ≥4 was reported in 454/1493 (30%) pts. Mean PsA duration was similar between the subset and the rest of the PALACE 1–3 population (BL BASDAI <4: n=1039). Slightly higher percentages of the subset had a history of palmoplantar, nail, scalp, or plaque psoriasis; mean BL psoriasis BSA and % with BSA ≥3% were slightly increased. The subset had higher mean BL values for CRP (1.12 vs 0.93), pain VAS (63.6 vs 53.8), pt's global disease assessment (62.2 vs 53.5), and physician's global disease assessment (PhGA) (59.0 vs 53.0) and markedly worse mean HAQ-DI (1.41 vs 1.08), SF-36v2 PF (30.6 vs 35.8), and FACIT-F (25.7 vs 31.8); TJC was higher (25.1 vs 19.1) and SJC (12.4 vs 10.9) was less differentiated. DAS-28 scores were comparable. Despite disease activity differences, BL concomitant oral DMARDs were similar in both groups: 1 in 61.0% and 2 in 5.5% (subset) vs 1 in 57.8% and 2 in 6.4% (rest of PALACE 1–3 population); MTX was the most common DMARD. In the subset, 73.6% had only been treated with oral DMARDs pre-study and 44.9% with only 1 DMARD; 25.1% had prior biologic use and 9% prior biologic failure, slightly higher percentages vs the other group. Small increases in BL NSAID and analgesic use were noted in the subset. Mean BL BASDAI scores in the subset were 6.6 in APR and 6.4 in placebo (PBO)pts. APR resulted in a greater mean decrease in BASDAI score vs PBO at Wk 16 (−1.53 vs −0.91; P=0.0173) and Wk 24 (−1.64 vs −0.74; P=0.0002); other disease measures significantly improved, including marked HAQ-DI, PhGA, and fatigue improvements (Table). Long-term improvement was seen across measures, with mean Wk 52 BASDAI reduction of −2.18 (Table) and mean HAQ-DI improvement of −0.464. Conclusions In this post-hoc analysis, pts reporting BASDAI ≥4 appear to have added disease burden, with greater disability, pain, fatigue, and global disease ratings; this may not be captured by some disease activity measures, and effective treatment strategies may not have been available. APR resulted in long-term improvements in BASDAI scores and other measures. Further evaluation objectively assessing presence of inflammatory spine disease in PsA and its response to APR is warranted. Disclosure of Interest P. Mease Grant/research support from: AbbVie Amgen, BiodenIdec, Bristol-Myers Squibb, Celgene, Genentech, Janssen, GlaxoSmithKline, Lilly, Merck, Novartix, Pfizer, UCB, Speakers bureau: AbbVie, Amgen, BiogenIdec, Bristol-Myers Squibb, Genentech, Janssen GlaxoSmithKline, Lilly, Pfizer, UCB, H. Marzo-Ortega: None declared, A. Poder: None declared, F. Van den Bosch Grant/research support from: AbbVie, Celgene Corporation, Janssen, Merck, Pfizer Inc, UCB, J. Wollenhaupt Consultant for: Abbott Laboratories, Bristol-Myers Squibb, MSD, Pfizer, and UCB, E. Lespessailles Grant/research support from: Novartis, Lilly, Servier, Amgen; Speaker's Bureau: Novartis and Lilly, M. McIlraith Employee of: Celgene Corporation, L. Teng Employee of: Celgene Corporation, S. Hall Grant/research support from: Amgen, AstraZeneca, Boehringer Ingelheim, Centocor, GlaxoSmithKline, MSD, Pfizer, Sanofi Aventis, Sanofi Pasteur, Schering-Plough, Serono, and Wyeth, Speakers bureau: Boehringer Ingelheim, GlaxoSmithKline, MSD, Pfizer, Roche, Sanofi Aventis, Schering-Plough, and Wyeth

Background Fatigue, a common symptom affecting individuals with psoriatic arthritis (PsA), is associated with decreased quality of life and loss of work productivity.1 The 2014 OMERACT PsA Working Group identified fatigue measurement as an important outcome to consider including in PsA core assessments.2 The PALACE 1 (NCT01172938), 2 (NCT01212757), and 3 (NCT01212770) studies compared apremilast (APR) efficacy/safety, including fatigue level, with placebo (PBO) in patients (pts) with active PsA despite prior conventional DMARDs and/or biologics. Objectives Report APR treatment impact on fatigue over 104 wks in a pooled analysis of the PALACE 1–3 studies. Methods Pts were randomized (1:1:1) to PBO, APR 30 mg BID (APR30), or APR 20 mg BID (APR20) stratified by baseline DMARD use. The PBO-controlled phase continued to Wk 24, with a Wk 16 early escape option. At Wk 24, all remaining PBO pts were re-randomized to APR30 or APR20. Double-blind APR treatment continued to Wk 52; pts could then continue to receive open-label APR up to an additional 4 years. Fatigue was assessed using FACIT-F v4 and SF-36v2 Vitality domain (VT).3 Total FACIT-F scores range from 0–52; lower scores denote higher fatigue levels. As a point of reference, mean fatigue scores of 40.1–43.6 in the general population,4,5 35.8 in PsA pts,6 and 23.9 in anemic cancer pts5 have been reported, and FACIT-F MCID in PsA has not been determined; this analysis used FACIT-F MCID in rheumatoid arthritis pts (3–4).7 SF-36v2 VT, a subscale of SF-36v2, measures physical and mental impact of fatigue on individuals.8 Scores are norm-based; group values <47 represent a below-average range vs the general population.9 Results Baseline mean FACIT-F (29.4–30.9) and SF-36v2 VT (40.6–40.8) scores were below population norms. Long-term improvement in fatigue was seen in APR pts at Wks 52 and 104 (mean FACIT-F=35.0), marking a shift toward population FACIT-F norms (Table). APR30 mean change was 5.6, with 50.9% of pts achieving FACIT-F MCID. Similarly, improvements in SF-36v2 VT scores were observed at Wks 52 and 104 with $≈ $60% of pts achieving MCID. Over 104 wks, most AEs were mild/moderate; in general, no increase was seen in AE incidence/severity with longer term exposure. Conclusions APR-treated pts experienced improvements in fatigue, as measured by FACIT-F and SF-36 VT scores. Over 104 wks, clinically meaningful improvements were maintained. APR demonstrated an acceptable safety profile and was generally well tolerated up to 104 wks. References Swain. Clin Sci (Lond). 2000;99:1–8. Tillett. J Rheumatol. 2015;42:2198–2203. Yellen. J Pain Symptom Manage. 1997;13:63–74. Webster. Health Qual Life Outcomes. 2003;179. Cella. Cancer. 2002;94:528–38. Chandran. Ann Rheum Dis. 2007;66:936–9. Cella. J Rheumatol. 2005;32:811–9. Ware. Med Care. 1992;30:473–83. Advantages of norm-based scoring. In Ware, ed. User9s Manual for the SF-36v2 Health Survey. 2nd ed. Lincoln, RI: QualityMetric Incorporated; 2007. Disclosure of Interest A. Kavanaugh Grant/research support from: Abbott, Amgen, Astra-Zeneca, Bristol-Myers Squibb, Celgene Corporation, Centocor-Janssen, Pfizer Inc, Roche, and UCB, Consultant for: Abbott, Amgen, Astra-Zeneca, Bristol-Myers Squibb, Celgene Corporation, Centocor-Janssen, Pfizer Inc, Roche, and UCB, D. Gladman Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, Celgene Corporation, Janssen, Pfizer Inc, Novartis, and UCB, Consultant for: AbbVie, Amgen, Bristol-Myers Squibb, Celgene Corporation, Janssen, Pfizer Inc, Novartis, and UCB, C. Edwards Grant/research support from: Celgene Corporation, Pfizer Inc, Roche, and Samsung, Consultant for: Celgene Corporation, Pfizer Inc, Roche, and Samsung, Speakers bureau: Abbott, Glaxo-SmithKline, Pfizer Inc, and Roche, A. Poder Grant/research support from: Celgene Corporation, F. Lioté: None declared, P. Bird Grant/research support from: Celgene Corporation, G. Schett Grant/research support from: Abbott, Celgene Corporation, Roche, UCB, Consultant for: Abbott, Celgene Corporation, Roche, UCB, D. Nguyen Employee of: Celgene Corporation, L. Teng Employee of: Celgene Corporation, P. Mease Grant/research support from: Abbott, Amgen, Biogen Idec, Bristol-Myers Squibb, Genentech, Janssen, Eli Lilly, Pfizer Inc, and UCB, Consultant for: Abbott, Amgen, Biogen Idec, Bristol-Myers Squibb, Genentech, Janssen, Eli Lilly, Pfizer Inc, and UCB, Speakers bureau: Abbott, Amgen, Biogen Idec, Bristol-Myers Squibb, Genentech, Janssen, Eli Lilly, Pfizer Inc, and UCB

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 randomized (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 rerandomized (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 rerandomized 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%). Clinically 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. ClinicalTrials.gov identifier: NCT01212757.