1. Highlights From San Francisco 2015
CCO Independent Conference Coverage* of the 2015 American College of Rheumatology/Association of Rheumatology Health Professionals Annual Meeting, November 7 – 11, 2015
*CCO is an independent medical education company that provides state-of-the-art medical information to healthcare professionals through conference coverage and other educational programs.
Jointly provided by Boston University School of Medicine and Clinical Care Options
This program is supported by independent educational grants from Celgene and UCB, Inc.

2. About These Slides
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3. Faculty
Vinod Chandran, MBBS, MD, DM, PhD Assistant Professor Consultant Rheumatologist Division of Rheumatology Department of Medicine University of Toronto University Health Network Toronto, Canada
Stanley B. Cohen, MD Clinical Professor Department of Internal Medicine University of Texas Southwestern Medical School Co-Director Division of Rheumatology Presbyterian Hospital Co-Medical Director Metroplex Clinical Research Center Dallas, Texas
This slide lists the faculty who were involved in the production of these slides.

4. Disclosures
Vinod Chandran, MBBS, MD, DM, PhD, has disclosed that he has received consulting fees from AbbVie, Amgen, Celgene, Janssen, Novartis, and UCB and funds for research support from AbbVie. Stanley B. Cohen, MD, has disclosed that he has received consulting fees and/or funds for research support from Amgen, Biogen, Bristol-Myers Squibb, Centocor/Janssen, Genentech, Johnson & Johnson, Pfizer, Merck, and Roche.
This slide lists the disclosure information of the faculty and staff involved in the development of these slides.

5. Treatment Studies in Rheumatoid Arthritis

6. RA-BEAM: Baricitinib for Biologic-Naive RA Pts With Inadequate Response to MTX
Randomized, double-blind, active- and placebo-controlled phase III trial
Baricitinib: oral Janus kinase (JAK) inhibitor
Wk 12: 1˚ endpoint of ACR20 BARI vs PBO
Randomized 3:3:2
Wk 24
Wk 52
Baricitinib 4 mg QD + MTX (n = 487)
Biologic-naive RA pts with inadequate response to MTX
(N = 1305)
Adalimumab 40 mg Q2W + MTX (n = 330)
Placebo QD + MTX
(n = 488)
Baricitinib 4 mg QD + MTX
BARI, baricitinib; CDAI, clinical disease activity index; DAS28-CRP, disease activity score in 28 joints calculated with C-reactive protein; mTSS, modified total Sharp score; MTX, methotrexate; PBO, placebo; Q2W, every 2 weeks; QD, every day; RA, rheumatoid arthritis; RF, rheumatoid factor; SJC, swollen joint count; TJC, tender joint count.
After 16 wks, inadequate responders switched to baricitinib 4 mg QD
Pts well matched at baseline
Duration of RA: yrs
RF positive: 90% to 92%
mTSS:
Mean SJC (of 66): 15-16
Mean TJC (of 68): 23
Mean CDAI score: 38
DAS28-CRP:
Slide credit: clinicaloptions.com
1. Taylor PC, et al. ACR/ARHP Abstract 2L.

7. RA-BEAM: Efficacy Results
Significant improvements also observed for baricitinib groups:
vs PBO: SDAI, CDAI, DAS28- CRP/ESR (all at 12/24 wks), mTSS (at 24/52 wks), pt- reported parameters
vs ADA: SDAI, CDAI, DAS28- CRP (all at 12/52 wks), pt- reported parameters
Outcome, %
BARI 4 mg (n = 487)
ADA (n = 330)
PBO
(n = 488)
ACR20
Wk 12
70*§
61* 40
Wk 24
74*§
66* 37
Wk 52
71‡ 62 NA
ACR50
45*‡
35* 17
51*
45* 19
56‡ 47
ACR70
19*§
13* 5
30*§
22* 8 31
ACR20, American College of Rheumatology ≥ 20% improvement criteria; ACR50, American College of Rheumatology ≥ 50% improvement criteria; ACR70, American College of Rheumatology ≥ 70% improvement criteria; ADA, adalimumab; CDAI, clinical disease activity index; DAS28-CRP, disease activity score in 28 joints using C‐reactive protein; DAS28-ESR, disease activity score in 28 joints calculated with erythrocyte sedimentation rate; mTSS, modified total Sharp score; NA, not applicable; PBO, placebo; SDAI, simple disease activity index.
Nonresponder imputation (NRI) analysis.
*P < .001 vs PBO. ‡P = .01 vs ADA. §P = .05 vs ADA.
Slide credit: clinicaloptions.com
1. Taylor PC, et al. ACR/ARHP Abstract 2L.

8. RA-BEAM: Safety Results
Wks 0-24
Wks 0-52
Outcome, n (%)
BARI 4 mg (n = 487)
ADA (n = 330)
PBO
(n = 488)
SAEs
23 (5)
6 (2)
22 (5)
38 (8)
13 (4)
Serious infections
5 (1)
2 (< 1)
7 (1)
10 (2)
5 (2)
AEs leading to DC
24 (5)
7 (2)
17 (3)
36 (7)
AEs leading to TI
48 (10)
29 (9)
45 (9)
72 (15)
38 (12)
TEAEs
347 (71)
224 (68)
295 (60)
384 (79)
253 (77)
Infections
176 (36)
110 (33)
134 (27)
233 (48)
145 (44)
Malignancies
3 (< 1)
Herpes zoster
4 (1)
11 (2)
Lymphoproliferative disorder
1 (< 1)
MACE
ADA, adalimumab; AE, adverse event; ALT, alanine aminotransferase; BARI, baricitinib; DC, discontinuation; Hb, hemoglobin; HDL, high density lipoprotein; LDL, low density lipoprotein; MACE, major adverse cardiovascular events; PBO, placebo; SAE, serious adverse event; TEAE, treatment-emergent adverse event; TI, temporary interruption.
Baricitinib treatment also decreased neutrophils vs PBO treatment
ALT, creatinine, LDL, and HDL levels also increased with baricitinib treatment vs PBO
Slide credit: clinicaloptions.com
1. Taylor PC, et al. ACR/ARHP Abstract 2L.

9. RA-BEGIN: BARI ± MTX for Treating DMARD-Naive/Limited RA Pts
Randomized, active-controlled phase III trial
ACR20, %* (Wk 24/Wk 52)
Randomized 4:3:4
Wk 24*
Wk 52
Baricitinib 4 mg QD + MTX QW (n = 215)
78†/73†
RA pts with no or ≤ 3 doses MTX and no prior non-MTX csDMARD or biologic use
(N = 584)
Baricitinib 4 mg QD (n = 159)
77‡/73†
MTX QW
(n = 210)
62/56
After 24 wks, inadequate responders switched to baricitinib 4 mg QD. *Primary endpoint: noninferiority (≤ 12% margin) of ACR20 for BARI 4 mg vs MTX at Wk 24. †P ≤ .001 vs MTX. ‡P = .01 vs MTX.
ACR20, American College of Rheumatology ≥ 20% improvement criteria; ACR50, American College of Rheumatology ≥ 50% improvement criteria; ACR70, American College of Rheumatology ≥ 70% improvement criteria; AE, adverse event; BARI, baricitinib; CDAI, clinical disease activity index; csDMARD, conventional synthetic disease-modifying antirheumatic drug; mTSS, modified total Sharp score; MTX, methotrexate; QW, every week; RA, rheumatoid arthritis; SAE, serious adverse event; SDAI, simple disease activity index; TEAE, treatment-emergent adverse event.
Baseline mean RA duration: yrs
BARI and BARI + MTX associated with significant improvements in ACR50/70, SDAI, CDAI vs MTX at Wks 24/52; BARI + MTX significantly improved mTSS at Wks 24/52
SAEs, TEAEs, herpes zoster incidence similar between groups; BARI + MTX associated with increased AEs leading to discontinuation, nonserious infections
Slide credit: clinicaloptions.com
2. Fleischmann R, et al. ACR/ARHP Abstract 1045.

10. TARGET: Sarilumab + csDMARDs for RA Pts With IR/Intolerance to TNFis
Randomized, double-blind, placebo-controlled phase III trial
Sarilumab: human monoclonal antibody directed against the interleukin-6 (IL-6) receptor
Wk 24
Sarilumab 200 mg SC Q2W + csDMARDs
(n = 184)
Pts with active moderate to severe RA and IR/ intolerance to TNFis and on stable csDMARD ≥ 12 wks prior to study
(N = 546)
Sarilumab 150 mg SC Q2W + csDMARDs
(n = 181)
Placebo SC Q2W + csDMARDs
(n = 181)
Rescue therapy eligibility at Wk 12 (SAR 200 mg Q2W): < 20% improvement in SJC or TJC for 2 consecutive assessments. csDMARDS = methotrexate, leflunomide, sulfasalazine, or hydroxychloroquine.
csDMARDs, conventional synthetic disease-modifying antirheumatic drugs; DAS28-CRP, disease activity score in 28 joints using C‐reactive protein; IR, inadequate responder; Q2W, every 2 weeks; RA, rheumatoid arthritis; SC, subcutaneous; SJC, swollen joint count; TJC, tender joint count; TNFi, tumor necrosis factor inhibitor.
Baseline characteristics:
RA duration: yrs; > 1 prior TNFi: 20.6% to 25.4%
Mean DAS28-CRP: ; mean TJC (/68): ; mean SJC (/66):
Slide credit: clinicaloptions.com
4. Fleischmann R, et al. ACR/ARHP Abstract 970.

11. TARGET: Key Results Outcome SAR 200 mg + csD (n = 184)
PBO + csD
(n = 181)
Wk 24 ACR20, %*
60.9†
55.8†
33.7
Wk 24 ACR50, %
40.8†
37.0†
18.2
Wk 24 ACR70, %
16.3§
19.9‡
7.2
Wk 12 HAQ-DI score, mean change*
-0.5¶
-0.5‖
-0.3
TEAE, n (%)
120 (65.2)
119 (65.7)
90 (49.7)
DC for TEAE, n (%)
17 (9.2)
14 (7.7)
8 (4.4)
ACR20, American College of Rheumatology ≥ 20% improvement criteria; ACR50, American College of Rheumatology ≥ 50% improvement criteria; ACR70, American College of Rheumatology ≥ 70% improvement criteria; CDAI, clinical disease activity index; csD, conventional synthetic disease-modifying antirheumatic drug; DAS28-CRP, disease activity score in 28 joints calculated with erythrocyte sedimentation rate; DC, discontinuation; HAQ-DI, Health Assessment Questionnaire Disability Index; PBO; placebo; TEAE, treatment-emergent adverse event.
*Coprimary endpoint. †P < vs PBO. ‡P = vs PBO. §P = vs PBO. ‖P = vs PBO. ¶P = vs PBO.
Sarilumab treatment also improved CDAI, DAS28-CRP, and HAQ-DI at Wk 24 vs PBO
Infections and infestations were the most commonly reported TEAE in all groups
Slide credit: clinicaloptions.com
4. Fleischmann R, et al. ACR/ARHP Abstract 970.

12. C-EARLY: Certolizumab Pegol + MTX for Early, DMARD-Naive RA
Randomized, double-blind, placebo-controlled phase III trial
Certolizumab pegol: tumor necrosis factor (TNF) blocker
Randomized 3:1
Wk 52
Certolizumab Pegol 200 mg SC Q2W* + MTX†
(n = 660)
DMARD-naive pts with active RA of < 1 yr duration and poor prognostic factors
(N = 879)
Placebo SC Q2W + MTX†
(n = 219)
*A loading dose of certolizumab pegol was given at Wks 0, 2, and 4 (CZP 400 mg + MTX). †MTX: started 10 mg/wk, increased up to 25 mg/wk by Wk 8. Pts could be withdrawn from the study at Wk 20 (worsening/no improvement) or 24 (insufficient improvement).
CZP, certolizumab pegol; DAS28-ESR, disease activity score in 28 joints calculated with erythrocyte sedimentation rate; DMARD, disease-modifying antirheumatic drug; MTX, methotrexate; Q2W, every 2 weeks; RA, rheumatoid arthritis; RF, rheumatoid factor; SC, subcutaneous; SJC, swollen joint count; TJC, tender joint count.
Pts well matched at baseline:
RF positive: 97%
Mean DAS28-ESR: ; mean TJC (/28): ; mean SJC (/28):
Slide credit: clinicaloptions.com
5. Weinblatt M, et al. ACR/ARHP Abstract 968.

13. C-EARLY: Key Results
Outcome
CZP + MTX
(n = 655)
PBO + MTX
(n = 213)
sREM,* %
28.9†
15.0
sLDA,‡ %
43.8†
28.6
Wk 52 ACR50, %
61.8§
52.6
TEAE, n (%)‖
525 (79.7)
158 (72.8)
DC for TEAE, n (%)‖
57 (8.6)
20 (9.2)
TEAEs leading to death, n (%)‖
2 (0.3)
1 (0.5)
*Primary endpoint: sustained remission (DAS28-ESR < 2.6 at Wk 40 sustained to Wk 52). †P < .001 vs PBO. ‡Sustained low disease activity (DAS28-ESR ≤ 3.2 at Wk 40 sustained to Wk 52). §P = .023 vs PBO. ‖Safety population: CZP, n = 659; PBO = 217.
ACR50, American College of Rheumatology ≥ 50% improvement criteria; CZP, certolizumab pegol; DAS28-ESR, disease activity score in 28 joints calculated with erythrocyte sedimentation rate; DC, discontinuation; HAQ-DI, Health Assessment Questionnaire Disability Index; mTSS, modified total Sharp score; MTX, methotrexate; PBO, placebo; sLDA, sustained low disease activity; sREM, sustained remission; TEAE, treatment-emergent adverse event.
Certolizumab pegol treatment was also associated with significant improvements in van der Heijde mTSS and HAQ-DI at Wk 52 vs PBO
Slide credit: clinicaloptions.com
5. Weinblatt M, et al. ACR/ARHP Abstract 968.

14. BALANCE I: ABT-494 for RA Pts With IR/Intolerance to TNFis
Randomized, double-blind, placebo-controlled phase IIb trial
ABT-494: oral JAK1 inhibitor
Primary endpoint: ACR20 at Wk 12
Baseline characteristics:
Mean duration from RA diagnosis: yrs
Prior treatment ≥ 2 prior TNFis: 24% to 31%
Mean TJC (/68): 26-30
Mean SJC (/66): 17-19
Mean DAS28-CRP:
Wk 12
ABT mg BID
(n = 55)
Active RA pts stably treated with MTX and with prior IR/intolerance to ≥ 1 TNFi
(N = 276)
ABT mg BID
(n = 55)
ACR20, American College of Rheumatology ≥ 20% improvement criteria; BID, twice daily; DAS28-CRP, disease activity score in 28 joints using C‐reactive protein; IR, inadequate response; SJC, swollen joint count; TJC, tender joint count; RA, rheumatoid arthritis; TNFi, tumor necrosis factor inhibitor.
ABT mg BID
(n = 55)
ABT mg BID
(n = 55)
Placebo BID
(n = 56)
Slide credit: clinicaloptions.com
6. Kremer JM, et al. ACR/ARHP Abstract 14L.

15. BALANCE I: Efficacy Results
Outcome, Wk 12
ABT-494
PBO (n = 56)
3 mg
(n = 55)
6 mg
12 mg
18 mg
ACR20, %
53*
58†
71‡
67‡ 34
ACR50, % 24
35*
42†
38† 16
ACR70, % 13
26†
22† 4
DAS28-CRP, ∆ from BL
-1.9†
-2.2‡
-2.3‡
-2.5‡
-1.1
CDAI ≤ 10, % 27 31 40 25
CDAI ≤ 2.8, % 9 11 7
ACR20, American College of Rheumatology ≥ 20% improvement criteria; ACR50, American College of Rheumatology ≥ 50% improvement criteria; ACR70, American College of Rheumatology ≥ 70% improvement criteria; CDAI, clinical disease activity index; DAS28-CRP, disease activity score in 28 joints using C‐reactive protein; PBO, placebo.
Nonresponder imputation analysis. *P < .05; †P < .01; ‡P < .001 vs PBO.
Slide credit: clinicaloptions.com
6. Kremer JM, et al. ACR/ARHP Abstract 14L.

16. BALANCE I: Safety Results
Outcome, Wk 12
ABT-494
PBO (n = 56)
3 mg (n = 55)
6 mg (n = 55)
12 mg (n = 55)
18 mg (n = 55)
AE, n (%)
26 (47)
31 (56)
37 (67)
39 (71)
25 (45)
SAE, n (%)
2 (4)
1 (2)
DC for AEs,* n (%)
6 (11)
3 (6)
Infection,† n (%)
11 (20)
12 (22)
22 (40)
21 (38)
13 (23)
Serious infection, n (%)
Herpes zoster, n (%)
LDL-C/HDL-C ratio
1.94
2.03
2.07
1.84
1.85
NK cells, % ∆ from BL
-16
-18‡
-28‡
-43‡ 16
AE, adverse event; BL, baseline; DC, discontinuation; Hb, hemoglobin; HDL-C, high density lipoprotein cholesterol; LDL-C, low density lipoprotein cholesterol; NK, natural killer; PBO, placebo; SAE, serious adverse event.
*No deaths occurred during the study. †Only 1 serious infection occurred (PBO group). ‡P < .001 vs PBO.
Mean Hb levels within normal range for all groups during the study; however, ABT mg or 6 mg treatment was associated with an increase in Hb levels from BL vs PBO
Slide credit: clinicaloptions.com
6. Kremer JM, et al. ACR/ARHP Abstract 14L.

17. ABP 501 (ADA Biosimilar) vs ADA for Treating Moderate to Severe RA
Randomized, double-blind, active-controlled phase III trial
Pts well matched at baseline
Mean RA duration: 9.4 yrs; prior biologic use: 26.9% to 28.2%
Mean DAS28-CRP: 5.7; mean TJC: ; mean SJC:
Baseline oral corticosteroid use: 49.6% to 50.8%
Wk 22
Adalimumab-naive adult pts with active moderate to severe RA on stable MTX; ineligible if treatment with ≥ 2 prior biologics
(N = 526)
ABP mg SC Q2W (n = 264)
Follow-up to Wk 24
Adalimumab 40 mg SC Q2W
(n = 262)
ADA, adalimumab; DAS28-CRP, disease activity score in 28 joints using C‐reactive protein; MTX, methotrexate; Q2W, every 2 weeks; RA, rheumatoid arthritis; SC, subcutaneous; SJC, swollen joint count; TJC, tender joint count.
Slide credit: clinicaloptions.com
12. Cohen SB, et al. ACR/ARHP Abstract 2054.

18. ABP 501 vs ADA: Key Results
Clinical equivalence in efficacy was demonstrated between ABP 501 and ADA (primary endpoint analysis)
Wk 24 Results, %
ABP 501 (n = 264)
ADA (n = 262)
ACR20*
74.6†
72.4
ACR50
49.2
52.0
ACR70
26.0
22.9
Any AE
50.0
54.6
Treatment-related SAE
1.5
0.4
DC for AE
2.7
0.8
Any injection-site reaction
2.3
5.0
Binding antibodies‡
38.3
38.2
Neutralizing antibodies‡
9.1
11.1
ACR20, American College of Rheumatology ≥ 20% improvement criteria; ACR50, American College of Rheumatology ≥ 50% improvement criteria; ACR70, American College of Rheumatology ≥ 70% improvement criteria; ADA, adalimumab; AE, adverse event; ; DC, discontinuation; SAE, serious adverse event; TEAE, treatment-emergent adverse event.
*Primary endpoint = risk ratio of ACR20 (ABP 501 vs ADA) at week 24. †Risk ratio: 1.04 (90% CI: ). ‡Any time post baseline.
Slide credit: clinicaloptions.com
12. Cohen SB, et al. ACR/ARHP Abstract 2054.

19. Treatment Studies in Spondyloarthritis

20. Biologic-naive adult pts with ≥ 6 mos active PsA
SPIRIT P1: Ixekizumab vs Adalimumab for Biologic-Naive Pts With Active PsA
Randomized, double-blind, active- and placebo-controlled phase III trial
Ixekizumab: monoclonal antibody to cytokine IL-17A
Wk 24
Ixekizumab 80 mg SC Q2W
(n = 103)
Ixekizumab 80 mg SC Q4W
(n = 107)
Biologic-naive adult pts with ≥ 6 mos active PsA
(N = 417)
Adalimumab 40 mg SC Q2W
(n = 101)
ADA, adalimumab; IR, inadequate responder; IXE, ixekizumab; MTX, methotrexate; PsA, psoriatic arthritis; Q2W, every 2 weeks; Q4W, every 4 weeks; SC, subcutaneous.
Placebo†
(n = 106)
Study not powered for direct comparisons between IXE and ADA groups. Pts in IXE arms received 160-mg IXE starting dose (2 injections). After 16 wks, IRs rescued with IXE 80 mg Q2W or Q4W.
Baseline, time from PsA diagnosis: yrs; current MTX use: 51.5% to %
Slide credit: clinicaloptions.com
14. Mease PJ, et al. ACR/ARHP Abstract 977.

21. SPIRIT P1: Efficacy Results
Wk 24 Outcomes
IXE Q2W (n = 103)
IXE Q4W (n = 107)
ADA (n = 101)
PBO (n = 106)
ACR20,* %
62†
58†
57† 30
ACR50, %
47†
40†
39† 15
ACR70, %
34†
23†
26† 6
PASI 75,‖ %
80†
71†
54† 10
PASI 100,‖ %
53†
43†
24‡ 3
HAQ-DI, ∆ from BL
-0.50†
-0.44†
-0.37‡
-0.18
mTSS, ∆ from BL
0.08†
0.17‡
0.10†
0.49
LEI, % pts LEI score 0¶ 33 19
LDI, % pts LDI-B score 0#
70†
67† 52 31
ACR20, American College of Rheumatology ≥ 20% improvement criteria; ACR50, American College of Rheumatology ≥ 50% improvement criteria; ACR70, American College of Rheumatology ≥ 70% improvement criteria; ADA, adalimumab; BL, baseline; BSA, body surface area; HAQ-DI, Health Assessment Questionnaire Disability Index; IXE, ixekizumab; LDI, Leeds Dactylitis Index; LEI, Leeds Enthesitis Index; mTSS, modified total Sharp score; PASI, psoriasis area and severity index 75%/90%/100% response rate; PBO, placebo; Q2W, every 2 weeks; Q4W, every 4 weeks.
*Primary endpoint (IXE vs PBO). †P ≤ .001; ‡P ≤ .01. ‖Only pts with ≥3% BSA at BL: IXE Q2W/Q4W/ADA/PBO, n = 59/73/68/67. ¶Only pts with BL LEI score > 0: IXE Q2W/Q4W/ADA/PBO, n = 57/68/54/57. #Only pts with BL LDI-B score > 0: IXE Q2W/Q4W/ADA/PBO, n = 37/46/21/36.
Slide credit: clinicaloptions.com
14. Mease PJ, et al. ACR/ARHP Abstract 977.

22. SPIRIT P1: Safety Results
Outcome, n (%)
IXE Q2W (n = 102)
IXE Q4W (n = 107)
ADA (n = 101)
PBO (n = 106)
TEAEs
67 (65.7)*
71 (66.4)*
65 (64.4)
50 (47.2)
Severe
5 (4.9)
4 (3.7)
1 (1.0)
2 (1.9)
SAEs
3 (2.9)
6 (5.6)
5 (5.0)
DC due to AE
4 (3.9)
2 (2.0)
Infections of special interest
Herpes zoster (n = 1) Esophageal candida (n = 1)
Oral candida (n = 1)
Any infection
24 (23.5)
30 (28.0)
26 (25.7)
27 (25.5)
Any Candida infection
1 (0.9)
Active or reactivated TB
Depression
Cytopenias
4 (4.0)
6 (5.7)
Neutropenia
Cerebro-cardiovascular event
3 (3.0)
Malignancy
Crohn’s disease or UC
ADA, adalimumab; AE, adverse event; IXE, ixekizumab; DC, discontinuation; PBO, placebo; Q2W, every 2 weeks; Q4W, every 4 weeks; SAE, serious adverse event; TB, tuberculosis; TEAE, treatment-emergent adverse event; UC, ulcerative colitis.
*P ≤ .001 vs PBO.
Slide credit: clinicaloptions.com
14. Mease PJ, et al. ACR/ARHP Abstract 977.

23. PALACE 3: Apremilast for Treating PsA: 104-Wk Efficacy and Safety
Randomized, double-blind, placebo-controlled phase III trial
Apremilast: oral inhibitor of phosphodiesterase 4
Stratified by BL DMARD use, PS involvment
Wk 24
Wk 52
Apremilast 30 mg BID
(n = 167)
Adult pts with PsA ≥ 6 mos and IR to DMARDs
(N = 505)
Apremilast 20 mg BID
(n = 169)
Open-label extension†
Placebo*
(n = 169)
Randomized to APR 30 mg or 20 mg
*PBO pts with IR at Wk 16 could be rescued to APR 20 mg or 30 mg. †Up to 4 additional yrs.
ACR20, American College of Rheumatology ≥ 20% improvement criteria; ACR50, American College of Rheumatology ≥ 50% improvement criteria; ACR70, American College of Rheumatology ≥ 70% improvement criteria; AE, adverse event; APR, apremilast; BID, twice daily; DAS28-CRP, disease activity score in 28 joints using C‐reactive protein; DC, discontinuation; DMARD, disease-modifying antirheumatic drug; HAQ-DI, Health Assessment Questionnaire Disability Index; IR, inadequate response; MCID, minimal clinically important difference; PASI, Psoriasis Area and Severity Index; PsA, psoriatic arthritis; SAE, serious adverse event.
Sustained relief observed at Wks 52 and 104 for pts treated with apremilast mg or 30 mg in terms of pts with DAS28 < 2.6, ACR20/50/70, PASI 50/75, and HAQ-DI score exceeding MCID ≥ 0.30
Most AEs mild/moderate; fewer pts discontinued between Wks 52 and than between Wks 0 and 52
Slide credit: clinicaloptions.com
21. Edwards CJ, et al. ACR/ARHP Abstract Based on abstract data.

24. MEASURE 2: 52-Wk Results for Secukinumab in Active AS
Randomized, double-blind, placebo-controlled phase III trial
Secukinumab: human monoclonal antibody to IL-17A
Stratified by prior TNFi
Wk 16*
Wk 256‡
Secukinumab 150 mg SC (n = 72)
AS pts with IR/intolerance to NSAIDs; TNFi naive or IR/intolerant
(N = 219)
Secukinumab 75 mg SC (n = 73)
Placebo SC†
(n = 74)
AS, ankylosing spondylitis; BASDAI, Bath Ankylosing Spondylitis Disease Activity Index; IR, inadequate response; NSAID, nonsteroidal antiinflammatory drug; Q4W, every 4 weeks; SC, subcutaneous; TNFi, tumor necrosis factor inhibitor.
Dosing occurred at baseline and QW Wks 1-4, then Q4W. *Primary endpoint. †After Wk 16, pts randomized to secukinumab 75 or 150 mg SC Q4W. ‡Final injection.
Baseline characteristics:
Time since AS diagnosis: yrs; mean BASDAI total score: ; mean total back pain (0-100 mm): mm; TNFi naive: 60.8% to 61.6%
Slide credit: clinicaloptions.com
22. Braun J, et al. ACR/ARHP Abstract 974.

25. MEASURE 2: Key Results
SECU 150 mg (n = 72)
SECU 75 mg (n = 73)
PBO (n = 74)
Outcome
Wk 16
Wk 52
ASAS20, %
61.1*
73.8
41.1
63.9
28.4 NA
ASAS40, %
36.1*
57.4
26.0
41.0
10.8
BASDAI score
-2.19*
-2.85
-1.92
-2.47
-0.85
DC for AE, n (%)†
6 (5.7)
4 (3.8)
4 (5.4)
Any AE, events (per 100 SY)†
87 (214.1)
88 (211.7)
47 (443.2)
Serious AE, events (per 100 SY)†
8 (6.6)
9 (7.7)
3 (14.0)
AE, adverse event; ASAS, Assessment of Spondyloarthritis International Society criteria; ASQoL, Ankylosing Spondylitis Quality of Life; DC, discontinued; hsCRP, high-sensitivity C-reactive protein; NA, not applicable; PBO, placebo; SECU, secukinumab; SF-36 PCS, Short Form (36) Health Survey Physical Component Summary; SY, subject-years.
*P < .001; †Safety population: SECU 150 mg/75 mg/PBO, n = 106/105/74.
Sustained benefits of secukinumab treatment were also observed for ASAS5/6, ASQoL, SF-36 PCS, and hsCRP measures
Slide credit: clinicaloptions.com
22. Braun J, et al. ACR/ARHP Abstract 974.

26. Tofacitinib for Biologic-Naive AS Pts
Randomized, double-blind, placebo-controlled, dose-ranging phase II trial
Tofacitinib: oral JAK inhibitor
Wk 12
Tofacitinib 10 mg BID
(n = 52)
Tofacitinib 5 mg BID
(n = 52)
Biologic-naive adult AS pts with IR or intolerance to NSAIDs (N = 208)*
Follow-up to Wk 16
Tofacitinib 2 mg BID
(n = 52)
AS, ankylosing spondylitis; BASDAI, Bath Ankylosing Spondylitis Disease Activity Index; BID, twice daily; DMARD, disease-modifying antirheumatic drug; IR, inadequate response; NSAID, nonsteroidal antiinflammatory drug.
*One pt not treated due to tibia/fibia fracture between screening and baseline.
Placebo
(n = 51)
Baseline characteristics:
Mean disease duration: yrs; mean BASDAI total score:
Concomitant DMARDs: 27.5% to 44.2%
Slide credit: clinicaloptions.com
28. van der Heijde D, et al. ACR/ARHP Abstract 5L.

27. Tofacitinib for AS: Key Results
Wk 12, %
Tofacitinib
PBO (n = 51)
2 mg (n = 52)
5 mg (n = 52)
10 mg (n = 52)
ASAS20 response (Emax model)*
56.0
63.0
67.4
40.1
Difference vs PBO (95% CI)
15.8 ( )
22.9 ( )
27.3 ( ) --
ASAS20 (observed)
51.9
80.8†
55.8
41.2
BASDAI 50
46.2‡
42.3‡
23.5
DC for AE
1.9
5.9
TEAEs
44.2
53.8
43.1
SAEs
3.9
AE, adverse event; AS, ankylosing spondylitis; ASAS, Assessments in Ankylosing Spondylitis improvement; ASDAS, Ankylosing Spondylitis Disease Activity Score; BASDAI, Bath Ankylosing Spondylitis Disease Activity Index; DC, discontinuation; MRI, magnetic resonance imaging; PBO, placebo; SAE, serious adverse event; SPARCC, Spondyloarthritis Research Consortium of Canada score; TEAE, treatment-emergent adverse event.
*Primary endpoint. †P < .001 vs PBO. ‡P < .05 vs PBO.
Tofacitinib treatment also associated with improvements in ASDAS, SPARCC MRI (joint and spine) scores vs PBO
Slide credit: clinicaloptions.com
28. van der Heijde D, et al. ACR/ARHP Abstract 5L.

28. Treatment Studies in Other Conditions

29. EMBODY 1 and 2: Epratuzumab for Moderate to Severe SLE
EMBODY 1 and 2: identical randomized, double-blind, placebo-controlled phase III trials; epratuzumab: humanized monoclonal antibody to CD22 on B cells
Wk 48
Epratuzumab 1200 mg IV QOW + SOC
(n = 266/263)
Adult pts with moderately to severely active SLE stably treated with corticosteroids*
(EMBODY 1/2: N = 793/791)
Epratuzumab 600 mg IV QW + SOC
(n = 262/262)
Placebo IV + SOC
(n = 265/266)
*Corticosteroids required; pts could continue antimalarials if received ≥ 12 wks prior to study (stable dose for ≥ 28 ± 1 days); pts could continue immunosuppressants if on stable dose for ≥ 28 ± 1 days.
BILAG, British Isles Lupus Activity Group; IV, intravenous; QW, every week; QOW, every other week; SLE, systemic lupus erythematosus; SLEDAI-2K, Systemic Lupus Erythematosus Disease Activity Index 2000; SOC, standard of care.
Baseline characteristics (EMBODY 1 and 2):
Concomitant drugs: corticosteroid: 97.3% to 99.6%; antimalarial: 61.3% to 74.2%; immunosuppressant: 43.3% to 50.4%
≥ 1 BILAG A score(s): 55.8% to 61.0%; ≥ 2 BILAG B scores: 48.4% to 53.3%; SLEDAI-2K score: ; musculoskeletal BILAG A/B: 92.2% to 93.5%; mucocutaneous BILAG A/B: % to 83.0%
Slide credit: clinicaloptions.com
32. Clowse MEB, et al. ACR/ARHP Abstract 4L.

30. EMBODY 1 and 2: Key Results
Wk 48, n (%)
EMBODY 1
EMBODY 2
EPZ 1200 mg
(n = 244)
EPZ 600 mg
(n = 248)
PBO
(n = 249)
(n = 261)
(n = 264)
(n = 263)
BICLA responders*
97 (39.8)
93 (37.5)
85 (34.1)
89 (34.1)
93 (35.2)
88 (33.5)
P value (vs PBO)
0.175
0.442
0.899
0.716
Any TEAEs†
228 (88.0)
211 (79.9)
222 (84.4)
220 (84.3)
230 (87.1)
255 (85.6)
Serious TEAEs†
44 (17.0)
48 (18.3)
45 (17.2)
50 (18.9)
45 (17.1)
DC for TEAEs†
16 (6.2)
11 (4.2)
27 (10.3)
24 (9.2)
18 (6.8)
12 (4.6)
Infusion Reaction TEAEs†
29 (11.2)
25 (9.5)
19 (7.2)
30 (11.5)
16 (16.1)
20 (7.6)
BICLA, BILAG-Based Composite Lupus Assessment; DC, discontinuation; EPZ, epratuzumab; PBO, placebo; TEAE, treatment-emergent adverse event.
*Primary endpoint. Nonresponder imputation analysis. †Safety population: EMBODY 1: EPZ 1200 mg/ 600 mg/PBO, n = 259/264/263; EMBODY 2: EPZ 1200 mg/600 mg/PBO, n = 261/264/263.
Epratuzumab decreased B-cell count vs placebo Wk 4 through Wk 48
Similar numbers of pts in all arms decreased or did not change their corticosteroid dose
No differences were noted between groups for physician- or pt-reported outcomes
32. Clowse MEB, et al. ACR/ARHP Abstract 4L. Based on abstract and presentation data.
Slide credit: clinicaloptions.com

31. Anifrolumab for Moderate to Severe SLE
Randomized, double-blind, placebo-controlled phase II trial
Anifrolumab: humanized monoclonal antibody to the interferon-alpha receptor
Stratified by SLEDAI score, corticosteroid dose, and IFN gene signature
Wk 48
Anifrolumab 1000 mg IV Q4W + SOC
(n = 104)
Adult pts w/ moderate to severe SLE stably treated with oral prednisone, antimalarial, or immunosuppressive
(N = 305)
Anifrolumab 300 mg IV Q4W + SOC
(n = 99)
Placebo IV Q4W + SOC
(n = 102)
BILAG, British Isles Lupus Activity Group; IFN, interferon; Q4W, every 4 weeks; SLE, systemic lupus erythematosus; SLEDAI-2K, Systemic Lupus Erythematosus Disease Activity Index 2000; SOC, standard of care.
Baseline characteristics:
Mean SLEDAI-2K score: ; mean BILAG 2004 score:
Slide credit: clinicaloptions.com
35. Furie R, et al. ACR/ARHP Abstract 3223.

32. Anifrolumab for Moderate to Severe SLE: Efficacy Results
Outcome
Anifrolumab
PBO (n = 102)
300 mg
(n = 99)
1000 mg
(n = 104)
Total
SRI(4) responders, (%), Day 169 (primary endpoint)*
34.3‡
28.8§ NA
17.6
IFNGS high, (%)‖‖
36.0#
28.2**
13.2
IFNGS low, (%)¶¶
29.2††
30.8‡‡
30.8
SRI(4) responders, (%), Day 365†
51.5‖
38.5¶
25.5
AEs, n (%)§§
84 (84.8)
90 (85.7)
174 (85.3)
78 (77.2)
SAEs, n (%)§§
16 (16.2)
18 (17.1)
34 (16.7)
19 (18.8)
AE leading to DC, n (%)§§
3 (3.0)
10 (9.5)
13 (6.4)
8 (7.9)
Herpes zoster, n (%)§§
5 (5.1)
15 (7.4)
2 (2.0)
AE, adverse event; ANIFR, anifrolumab; BICLA, BILAG-Based Composite Lupus Assessment; CLASI, Cutaneous Lupus Erythematosus Disease Area and Severity Index; DC, discontinuation; IFNGS, interferon gene signature; OCS, oral corticosteroid; PBO, placebo; SAE, serious adverse event; SLE, systemic lupus erythematosus; SRI, Systemic Lupus Erythematosus Responder Index.
OCS tapered through treatment: < 10 mg/day and ≤ Day 1 dose maintained between Days 85 and 169* or Days 281 and 365†. ‡P = .014; §P = .063; ‖P < .001; ¶P = .048; #P = .004; **P = .029; ††P = .946; ‡‡P = .953 vs PBO. §§Safety population: ANIFR 300 mg/1000 mg/total/PBO, n = 99/105/204/101. ‖‖N = 229. ¶¶N = 76.
Anifrolumab 300/1000 mg significantly improved SRI(5) and BICLA responses and reduced CLASI activity to Day 365
35. Furie R, et al. ACR/ARHP Abstract Based on abstract and presentation data.
Slide credit: clinicaloptions.com

33. Tocilizumab for Giant Cell Arteritis
Randomized, single center, placebo-controlled phase II trial; tocilizumab: monoclonal antibody to the IL-6 receptor
Wk 52
Pts older than 50 yrs of age with newly diagnosed or recurrent GCA
(N = 30)
Tocilizumab* Q4W + GC
(n = 20)
Placebo Q4W + GC
(n = 10)
Primary endpoint: complete remission (normal ESR and CRP + absence of signs and symptoms) at Wk 12. GC started at 1 mg/kg/day and tapered to 0.1 mg/kg/day by Wk 12; after Wk 12, decreased by 1 mg/day to 0 mg. *8 mg/kg of body weight IV dose.
CRP, C-reactive protein; ESR, erythrocyte sedimentation rate; GC, glucocorticoid; GCA, giant cell arteritis; IV, intravenous; PBO, placebo; Q4W, every 4 weeks; TCZ, tocilizumab.
After 12 wks, significantly more pts in TCZ group experienced complete remission vs pts in PBO group (17/20 [85%] vs 4/10 [40%], P = .03)
At study end, significantly more pts in the TCZ group had experienced no relapse vs pts in PBO group (17/20 [85%] vs 2/10 [20%], HR = .05 [95% CI ], P = .008)
SAEs: 7/20 (35%) of pts receiving TCZ, 5/10 (50%) of pts receiving PBO
Slide credit: clinicaloptions.com
36. Adler S, et al. ACR/ARHP Abstract 1L.

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