• During the PBO-controlled period, there were no reports of IBD events in PsA, non-PsA pSpA, RA, uveiti s, HS, adult and pediatric Ps, pJIA, and peds ERA trials (Table 2) Table 2. Incidence of IBD Events in Pati ents From PBO-controlled Period of ADA Clinical Trials Indication Adalimumab (ADA) Placebo (PBO) N (PYs) All IBD AEs, n IR/100 PYs (95% CI) N (PYs) All IBD AEs, n IR/100 PYs (95% CI) All ADA trialsa 5774 (2065.6) 1 <0.1 (0.0–0.3) 3102 (1041.8) 1 0.1 (0.0–0.5) All SpAb 856 (261.5) 1 0.4 (0.0–2.1) 655 (192.9) 1 0.5 (0–2.9) PsA 202 (77.8) 0 0.0 211 (81.1) 0 0.0 Non-PsA pSpA 84 (19.1) 0 0.0 81 (18.8) 0 0.0 All axSpAc 570 (164.6) 1 0.6 (0.0–3.4) 363 (93.0) 1 1.1 (0.0–6.0) nr-axSpA 95 (21.5) 0 0.0 97 (22.2) 1 4.5 (0.1–25.1) AS 475 (143.1) 1 0.7 (0.0–3.9) 266 (70.8) 0 0.0 Rheumatoid Arthritis 2687 (1136.5) 0 0.0 1154 (481.1) 0 0.0 Uveitis 119 (64.4) 0 0.0 120 (47.4) 0 0.0 Hidradenitis suppurativa 419 (103.1) 0 0.0 366 (85.8) 0 0.0 Adult psoriasis 1594 (461.2) 0 0.0 727 (206.0) 0 0.0 All JIAd 99 (38.7) 0 0.0 80 (28.6) 0 0.0 aAll ADA- and PBO-treated adult and pediatric pati ents in all interventi onal studies excluding Crohn’s disease and ulcerati ve coliti s. bAll ADA- and PBO-treated pati ents in all interventi onal studies of PsA, non-PsA pSpA, nr-axSpA, and AS. cAll ADA- and PBO-treated pati ents in all interventi onal studies of nr-axSpA and AS. dAll ADA- pati ents in all interventi onal studies of pJIA and peds ERA. IBD = infl ammatory bowel disease; PBO = placebo; ADA = adalimumab; PYs = pati ent years; AEs = adverse events; IR = incidence rates; CI = confi dence interval; SpA = spondyloarthriti s; PsA = psoriati c arthriti s; pSpA = non-PsA peripheral spondyloarthriti s; axSpA = axial spondyloarthriti s; nr-axSpA = non-radiographic axSpA; AS = ankylosing spondyliti s; pJIA = polyarti cular juvenile idiopathic arthriti s; peds ERA = pediatric enthesiti s-related arthriti s. • Overall, the incidence rate for IBD events in ADA-treated pati ents during PBO-controlled periods and open-label extensions across all interventi onal trials included in this analysis was 0.1/100 PYs (Table 3) • The rates of IBD events varied across therapeuti c indicati ons from <0.1 to 0.8/100 PYs BACKGROUND • Adalimumab (ADA) is approved for the treatment of Crohn’s disease (CD) and ulcerati ve coliti s (UC); therefore, it is postulated that new onset or fl are of infl ammatory bowel disease (IBD) is a rare occurrence in ADA clinical trials for non-IBD indicati ons OBJECTIVE • The purpose of this analysis was to determine the rates of IBD adverse events (AEs) in ADA clinical trials, parti cularly in spondyloarthriti s (SpA) pati ents who are at a higher risk of IBD as a feature of SpA Incidence of Infl ammatory Bowel Disease Events in Adalimumab Clinical Trials Across Indicati ons Jeff rey R Curti s1, Dirk Elewaut2, Su Chen3, Maja Hojnik4, Navit Naveh5, Jaclyn K Anderson3 1Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, Alabama, United States; 2VIB Infl ammati on Research Center, University of Gent, Gent, Belgium; 3AbbVie Inc., North Chicago, Illinois, United States; 4AbbVie, Ljubljana, Slovenia; 5AbbVie, Hod HaSharon, Israel CONCLUSIONS � The rates of IBD AEs in ADA clinical trials were generally low across all indicati ons, with all events occurring in adult pati ents � Axial SpA pati ents are generally at higher risk of manifesti ng IBD – In the combined group of axSpA pati ents (AS and nr-axSpA), the rates of IBD for ADA-treated pati ents were numerically lower than for PBO-treated pati ents – In AS pati ents, the rates of IBD for ADA- and PBO-treated pati ents were low (0.7/100 PYs [95% CI, 0.4–1.1] and 0.0, respecti vely) and were similar to published PBO rates pooled across multi ple AS clinical trials with TNF inhibitors (1.3/100 PYs [95% CI, 0.2–4.8])1 � In pati ents at risk for IBD who require biologic therapy, ADA is a reasonable therapeuti c opti on based on the observed low IBD event rates in ADA clinical trials and its demonstrated effi cacy in treati ng UC and CD pati ents FRI0444 RESULTS DISCLOSURES JR Curti s has received research grants and/or consulti ng fees from Amgen, BMS, Corrona, Crescendo, Janssen, Pfi zer, and UCB. D Elewaut has received research grants, consulti ng fees, and/or speaker’s fees from AbbVie. S Chen, M Hojnik, N Naveh, and JK Anderson are employees of AbbVie and may own stock/opti ons. REFERENCES 1. Braun, J. et al. Arthriti s & Rheum. 2007;57:639–47. ACKNOWLEDGMENTS AbbVie funded the studies, contributed to their design, and parti cipated in data collecti on, analysis and interpretati on of the data, and in writi ng, review, and approval of the publicati on. Medical writi ng support was provided by Deepa Venkitaramani, PhD, of AbbVie. ASSESSMENT FOR INFLAMMATORY BOWEL DISEASE IBD • The search criteria for IBD events included the following standardized MedDRA queries preferred terms and did not disti nguish between new onset IBD and fl are of pre-existi ng disease: – Infl ammatory bowel disease (IBD) – Ulcerati ve coliti s (UC) – Crohn’s disease (CD) – IBD-not otherwise specifi ed (NOS) – Ulcerati ve procti ti s • In additi on to the MedDRA queries, manual assessment to disti nguish new-onset IBD and fl are of pre-existi ng disease was performed for events occurring in pati ents with axial SpA (nr-axSpA and AS) STATISTICAL ANALYSES • IBD events were defi ned as an IBD fl are in pati ents with pre-existi ng IBD, or new onset IBD among those without pre-existi ng IBD • Incidence rates of IBD events (combined new onset and fl are) were calculated separately for placebo (PBO)- and ADA-treated pati ents during the PBO-controlled periods of interventi onal clinical trials of ADA • Overall incidence rates of IBD events were determined in pati ents treated with ADA during the PBO-controlled periods and open-label extensions of all interventi onal clinical trials of ADA • The risk of an IBD event over a 1-year period of ADA treatment was also calculated – Due to variable follow-up durati on in the studies included in this analysis the ti me period included was limited to 1 year to improve comparability between studies • Incidence rates of IBD events are reported as events per 100 pati ent-years (PYs) • 95% confi dence intervals (CI) were based on exact Poisson confi dence limits • In SpA, the overall rate of IBD was 0.5/100 PYs, while the rates were 0, 0.8, 0.5, and 0.7/100 PYs in PsA, non-PsA pSpA, nr-axSpA, and AS, respecti vely (Table 3) – 2216 pati ents with axSpA (AS: 2026, nr-axSpA: 190) were exposed to ADA; in AS, 14 IBD events (7 new onset and 7 fl ares) were reported in 12 pati ents (7 new onset and 5 fl ares), while in nr-axSpA, 2 IBD events were reported in 1 pati ent (2 fl ares) • There were no reports of IBD events in pediatric pati ents Table 3. Incidence of IBD Events in Pati ents From All Non-registry ADA Clinical Trials Indication N (PYs) All IBD AEs, n IR/100 PYs (95% CI) All ADA trialsa 23 735 (36 404.6) 40 0.1 (0.1–0.2) All SpAb 3218 (3919.9) 19 0.5 (0.3–0.8) PsA 837 (997.5) 0 0.0 Non-PsA pSpA 165 (390.7) 3 0.8 (0.2–2.2) All axSpAc 2216 (2531.7) 16 0.6 (0.4–1.0) nr-axSpA 190 (412.2) 2 0.5 (0.1–1.8) AS 2026 (2119.5) 14 0.7 (0.4–1.1) Rheumatoid Arthritis 15 152 (24 813.0) 16 <0.1 (0.0–0.1) Uveitis 387 (538.8) 1 0.2 (0.0–1.0) Hidradenitis suppurativa 733 (836.3) 3 0.4 (0.1–1.1) Adult psoriasis 3500 (5268.7) 1 <0.1 (0.0–0.1) Pediatric psoriasis 111 (121.5) 0 0.0 All JIAd 274 (797.4) 0 0.0 aAll ADA adult and pediatric pati ents during PBO-controlled periods and open-label extensions across all interventi onal studies excluding Crohn’s disease, ulcerati ve coliti s, and intesti nal Behcet’s disease. bAll ADA pati ents in all interventi onal studies of PsA, non-PsA pSpA, nr-axSpA, and AS. cAll ADA pati ents in all interventi onal studies of nr-axSpA and AS. dAll ADA pati ents in all interventi onal studies of JIA, pJIA, and peds ERA. IBD = infl ammatory bowel disease; ADA = adalimumab; PYs = pati ent years; AEs = adverse events; IR = incidence rates; CI = confi dence interval; SpA = spondyloarthriti s; PsA = psoriati c arthriti s; pSpA = non-PsA peripheral spondyloarthriti s; axSpA = axial spondyloarthriti s; nr-axSpA = non-radiographic axSpA; AS = ankylosing spondyliti s; JIA = juvenile idiopathic arthriti s; pJIA = polyarti cular juvenile idiopathic arthriti s; peds ERA = pediatric enthesiti s-related arthriti s. • The risk of an IBD event occurring over a 1-year period in all interventi onal ADA trials was 0.1/100 PYs (Table 4) • The 1-year risk of an IBD event was <0.1/100 PYs in both RA and Ps trials • The 1-year risk of an IBD event was 0.0 in PsA, uveiti s, HS, pediatric Ps, pJIA, and peds ERA trials, since no IBD event was reported through 1 year of ADA treatment Table 4. Risk of IBD Event Over 1-year in Pati ents From All Non-registry ADA Clinical Trials Indication N (PYs) All IBD AEs, n IR/100 PYs (95% CI) All ADA trialsa 23 735 (15 366.7) 15 0.1 (0.1–0.2) All SpAb 3218 (1711.4) 8 0.5 (0.2–0.9) PsA 837 (491.6) 0 0.0 Non-PsA pSpA 165 (154.1) 1 0.6 (0.0–3.6) All axSpAc 2216 (1065.7) 7 0.7 (0.3–1.4) nr-axSpA 190 (166.0) 1 0.6 (0.0–3.4) AS 2026 (899.6) 6 0.7 (0.2–1.5) Rheumatoid Arthritis 15 152 (10 072.3) 6 <0.1 (0.0–0.1) Uveitis 387 (306.3) 0 0.0 Hidradenitis suppurativa 733 (591.0) 0 0.0 Adult psoriasis 3500 (2245.9) 1 <0.1 (0.0–0.2) Pediatric psoriasis 111 (96.6) 0 0.0 All JIAd 274 (234.4) 0 0.0 aAll ADA adult and pediatric pati ents in all interventi onal studies excluding Crohn’s disease, ulcerati ve coliti s, and intesti nal Behcet’s disease. bAll ADA pati ents in all interventi onal studies of PsA, non-PsA pSpA, nr-axSpA, and AS. cAll ADA pati ents in all interventi onal studies of nr-axSpA and AS. dAll ADA pati ents in all interventi onal studies of JIA, pJIA, and peds ERA. IBD = infl ammatory bowel disease; ADA = adalimumab; PYs = pati ent years; AEs = adverse events; IR = incidence rates; CI = confi dence interval; SpA = spondyloarthriti s; PsA = psoriati c arthriti s; pSpA = non-PsA peripheral spondyloarthriti s; axSpA = axial spondyloarthriti s; nr-axSpA = non-radiographic axSpA; AS = ankylosing spondyliti s; JIA = juvenile idiopathic arthriti s; pJIA = polyarti cular juvenile idiopathic arthriti s; peds ERA = pediatric enthesiti s-related arthriti s. • ADA was administered to 23 735 pati ents, representi ng 36 404.6 PYs of exposure • Incidence rates for IBD events during the PBO-controlled period of ADA interventi onal trials were <0.1/100 PYs for both ADA- and PBO-treated pati ents (Table 2) • In axSpA, the IBD rates in ADA- and PBO-treated pati ents during PBO-controlled period were 0.6/100 PYs and 1.1/100 PYs, respecti vely (Table 2) – There was only 1 IBD event reported in a pati ent on ADA treatment (in an AS pati ent) and 1 IBD event reported in pati ents treated with PBO (in a nr-axSpA pati ent) METHODS CLINICAL TRIALS • The rates of IBD AEs in 73 phase 2–4 interventi onal ADA clinical trials in rheumatoid arthriti s (RA), polyarti cular juvenile idiopathic arthriti s (pJIA), pediatric enthesiti s-related arthriti s (peds ERA), uveiti s (non-infecti ous intermediate, posterior, or pan-uveiti s), hidradeniti s suppurati va (HS), adult and pediatric psoriasis (Ps), psoriati c arthriti s (PsA), non-PsA peripheral SpA (pSpA), non-radiographic axial spondyloarthriti s (nr-axSpA), and ankylosing spondyliti s (AS) were analyzed (Table 1) • Trials in UC, CD, and intesti nal Behcet’s disease (BD) were excluded from this analysis; however, pati ents with UC, CD, and BD were not excluded from the trials included in this analysis Table 1. List of Indicati ons and Clinical Trials Indication No. of Trials No. of Patients All ADA trialsa 73 23 735 Psoriatic arthritis (PsA) 4 837 Non-PsA peripheral spondyloarthritis (pSpA) 1 165 Non-radiographic axial spondyloarthritis (nr-axSpA) 1 190 Ankylosing spondylitis (AS) 5 2026 Rheumatoid arthritis 35 15 152 Uveitis 2 387 Hidradenitis suppurativa (HS) 4 733 Adult psoriasis 16 3500 Pediatric psoriasis 1 111 All juvenile idiopathic arthritisb 4 274 aAll ADA adult and pediatric pati ents in all interventi onal studies excluding Crohn’s disease, ulcerati ve coliti s, and intesti nal Behcet’s disease. bAll ADA pati ents in all interventi onal studies of pJIA, and peds ERA. pJIA = polyarti cular juvenile idiopathic arthriti s; peds ERA = pediatric enthesiti s-related arthriti s. FC17PosterAbbVieCurtisIncidenceofInflammatoryBowel.pdf