Table S1: ICD-9-CM codes for patient enrollment from HIS (main or secondary diagnoses)

Transcription

1 Appendix (Table S1-S16) Table S1: ICD-9-CM codes for patient enrollment from HIS (main or secondary diagnoses) ICD-9-CM CODES DISEASE 555 Crohn s disease 556 (EXCLUDING: 556.0, 566.1, 556.4,556.8) Ulcerative colitis Table S2: Codes for patient enrollment from copayment exemption register CODES DISEASE Crohn s disease Ulcerative colitis Table S3: ICD-9-CM codes for exclusion criteria from diagnosis reported in discharge abstract (main or secondary) ICD-9-CM CODES DISEASE 714 Rheumatoid arthritis Psoriatic arthritis Ankylosing spondylitis Table S4: ATC codes for exclusion criteria from drug utilization in the year before index date: ATC Active agent Therapeutic area L01XC02 Rituximab Rheumatoid arthritis, Leukemia, Lymphocytic Chronic B- Cell,Non-Hodgkin lymphoma L04AA13 Leflunomide Psoriatic arthritis, Rheumatoid arthritis L04AA24 Abatacept Juvenile rheumatoid arthritis, Rheumatoid arthritis, L04AB01 Etanercept Juvenile rheumatoid arthritis, Psoriatic arthritis, Rheumatoid arthritis, Psoriasis, Ankylosing spondylitis, L04AB05 Certolizumab pegol Rheumatoid arthritis, L04AC03 Anakinra Rheumatoid arthritis, L04AC07 Tocilizumab Juvenile rheumatoid arthritis, Rheumatoid arthritis

2 Table S5: ICD-9-CM codes for comorbid conditions, registered in the 12 months preceding the index date ICD-9-cm codes Co-morbidity Ischemic disease 428 Congestive Heart failure Cerebrovascular Diseases Dementia Peripheral vascular disease Diabetes , 311, , 300.4, 309.0, Anxiety 334.1,336.2,348.1,3483,784.3,333.4,333.5, , Neurological disease 331,332,334,335, 341, 345, , , 311, , 293.8, 299.1, 331.0, Psychiatric 294.1, 300.4, 309.0, , V42.0, V45.1, procedures Renal disease (38.95,39.95,54.98,55.6) Liver Disease Hypertension

3 Table S6: ICD-9-CM codes used to characterize disease course, registered in the 12 months preceding the index date Condition ICD9cm code Description Anemia / malabsorption Secondary to blood loss (chronic) Iron deficiency anemia, unspecified Unspecified intestinal malabsorption Intestinal stenosis / obstruction Stenosis of rectum and anus Acute pseudo-obstruction of intestine Mural thickening causing obstruction Unspecified intestinal obstruction Stenosis of rectum and anus Other obstruction of duodenum Atresia and stenosis of large intestine, rectum, and anal canal Intestinal fistula / abscess/ ulcer Fistula of stomach or duodenum Fistula of intestine, excluding rectum and anus Fistula of bile duct Fistula of gallbladder Intestinoureteral fistula Urethral fistula Anal fistula 619 Fistula involving female genital tract Intestinovesical fistula 566 Abscess of anal and rectal regions Abscess of intestine Ulceration of intestine Ulcer of anus and rectum Perforation of intestine Haemorrhage 578 Gastrointestinal hemorrhage Hemorrhage of gastrointestinal tract, unspecified Hemorrhage of rectum and anus Blood in stool

4 Table S7: ATC codes for drug prescription patterns, registered in the year preceding the index date Drug Class Generic Name ATC code Antimetabolites Mercaptopurine L01BB02 Methotrexate L01BA01 Immunosuppressants Azathioprine L04AX01 Intestinal Antiinfectives Rifaximin A07AA11 Steroids Corticosteroids acting locally A07EA Corticosteroids for systemic use H02 Aminosalicylic acid and similar agents Mesalamine A07EC02 Sulfasalazine Balsalazide A07EC01 A07EC04 Antibacterials Metronidazole J01XD01 Ciprofloxacin J01MA02

5 Table S8: ICD-9-CM procedure codes for IBD-related bowel surgery used as effectiveness outcomes ICD-9-CM codes Procedure 458 Tot Intra-Abd Colectomy 485 Abd-Perineal Rect Resect 4561 Mult Seg Sm Bowel Excis 4562 Part Sm Bowel Resect Nec 4563 Total Removal Sm Bowel 4571 Mult Seg Lg Bowel Excis 4572 Cecectomy 4573 Right Hemicolectomy 4574 Transverse Colon Resect 4575 Left Hemicolectomy 4576 Sigmoidectomy 4579 Part Lg Bowel ExcisNec 4590 Intestinal Anastom Nos 4591 Sm-To-Sm Bowel Anastom 4592 Sm Bowel-Rect Stump Anas 4593 Small-To-Large Bowel Nec 4594 Lg-To-Lg Bowel Anastom 4595 Anal Anastomosis 4610 Colostomy Nos 4611 Temporary Colostomy 4613 Permanent Colostomy 4614 Delay Opening Colostomy 4620 Ileostomy Nos 4621 Temporary Ileostomy 4622 Continent Ileostomy 4623 Permanent Ileostomy Nec 4624 Delay Opening Ileostomy 4841 Soave SubmucRect Resect 4849 Pull-Thru RectResecNec 4861 TranssacRectosigmoidect 4862 Ant Rect Resect W Colost 4863 Anterior Rect Resect Nec 4864 Posterior Rect Resection 4865 Duhamel Rectal Resection 4869 Rectal Resection Nec

6 Table S9: List of serious and opportunistic infections used as safety outcome, registered in discharge abstract (principal or secondary diagnosis) after index date and throughout followup. ICD-9-CM codes Description Tuberculosis 31 Diseases due to other mycobacteria 36 Meningococcal infection 38 Septicemia 42 Human immunodeficiency virus [HIV] disease Subacute sclerosing panencephalitis Progressive multifocal leukoencephalopathy 53 Herpes zoster 54 Herpes simplex 75 Infectious mononucleosis Cytomegaloviral disease convert to ICD-10-CM Retrovirus in conditions classified elsewhere and of unspecified site Respiratory syncytial virus (RSV) convert to ICD-10-CM Other specified viral and chlamydial infections Mycoses 130 Toxoplasmosis 131 Trichomoniasis

7 Table S10: Patients discharged from hospital after index date and throughout follow-up with diagnosis (principal or secondary) of any of the following conditions. Disease CD CU Condition Infusion reaction (ICD-9-CM codes: 995.0, 995.2, 995.3) Dermomiosytis (ICD-9-CM codes: 710.3) Brain neoplasm (ICD-9-CM codes: 191.9) Acquired hemolytic anemias (ICD-9-CM codes: 283.0, 283.1, , , , 283.2, 283.9) IFX (N=367) ADA (N=505) IFX (N=469) ADA (N=91) Sum % Sum % Sum % Sum %

8 Figure 1: Unadjusted time to event analysis, Kaplan-Meier survivor curves for drug discontinuation or switch*, among CD or UC patients. As treated study design. Drug discontinuation or switch Crohn's disease Proportion of patients free of events Log-rank test Pr>chi2 < ADA IFX Time (years) Number at risk (events) 505 (35) 470 (70) 400 (44) 319 (41) (33) 334 (30) 304 (21) 259 (14) 216 exp = ADA exp = IFX Drug discontinuation or switch Ulcerative colitis Proportion of patients free of events Log-rank test Pr>chi2 < ADA IFX Time (years) Number at risk (events) 90 (12) 78 (18) 60 (10) 43 (11) (28) 439 (24) 415 (23) 362 (12) 310 exp = ADA exp = IFX * Whichever comes first. IFX: Infliximab, ADA: Adalimumab.

9 Table S11: Patient characteristics included in the predictive model (Intention to treat study design): Results of stepwise Cox regression models. Hazard ratios for abdominal surgery and serious and opportunistic infections among Crohn s disease patients Characteristic HR (Abdominal surgery) LCL UCL P-Value Gender Male Female Age class (years) > Intestinal obstruction/stenosis No Yes Previous surgery No Yes Number of comorbidities None or more Characteristic HR (Infections) LCL UCL P-Value Intestinal fistola/ulcera/abscess No Yes Number of comorbidities None or more

10 Table S12: Patient characteristics included in the predictive model (Intention to treat study design): Results of stepwise Cox regression models. Hazard ratios for corticosteroids utilization (60 days after index date) among Crohn s disease patients Characteristic Remote or no users Previous steroid utilization (within 365 days before index date) Recent users HR* LCL UCL P-Value HR* LCL UCL P-Value Time from last evidence of IBD from HIS to index date More than 5 years before index date Within 5 years before index date Number of comorbidities None or more Anemia/hemorrage No Yes Intestinal obstruction/stenosis No Yes Age class (years) > Previous aminosalicylic acid prescription Remote or no user Recent user * HR of corticosteroids utilization (60 days after index date) Previous drugs utilization (within 365 days before index date) - Recent: last prescription <= 6 months before index date - Remote or no users: last prescription > 6 months before index date or no prescriptions

11 Table S13: Patient characteristics included in the predictive model (Intention to treat study design): Results of stepwise Cox regression models. Hazard ratios for corticosteroids utilization (60 days after index date) among Ulcerative colitis patients Remote or no users Previous steroid utilization (within 365 days before index date) Recent users Characteristic HR* LCL UCL P-Value HR* LCL UCL P-Value Place of residence Rome municipality Rome province Other Lazio provinces Age class (years) > Number of comorbidities None or more Previous immunosuppressant prescription Remote or no user Recent user Anemia/hemorrage No Yes * HR of corticosteroids utilization (60 days after index date) Previous drugs utilization (within 365 days before index date) - Recent: last prescription <= 6 months before index date - Remote or no users: last prescription > 6 months before index date or no prescriptions

12 Table S14: Patient characteristics included in the propensity score. Characteristics of Crohn s Disease patients according to exposure before and after adjustment for propensity score quintile. Infliximab Adalimumab n=367 n=505 p-value After adjustement for propensity score quintile N % N % p-value Gender Male Female Age class (years) > Residence Rome municipality Rome province Other Lazio provinces CD disease form (ICD9-CM code) Regional enteritis of small intestine (555.0) Regional enteritis of large intestine (555.1) Regional enteritis of small intestine with large intestine (555.2) Regional enteritis of unspecified site (555.9) CU diagnosis in CD patients Patients not discharge within 5 years before index date Time from last evidence of IBD from HIS to index date Within 5 years before index date More than 5 years before index date Risk factors for surgery Intestinal fistola/ulcera/abscess Drug exposure Corticosteroid (local/systemic) No Recent (<= 6 months) Remote (>6 months)

13 Table S15: Patient characteristics included in the propensity score. Characteristics of Ulcerative colitis patients according to exposure before and after adjustment for propensity quintile score Infliximab Adalimumab n=467 n=90 p-value After adjustement for propensity score quintile N % N % p-value Gender Male Female Age class > Residence Rome municipality Rome province Other Lazio provinces UC disease form (ICD9-CM code) Ulcerative enterocolitis/ulcerative ileocolitis/pseudopolyposis of colon (556.0/ 556.1/ 556.4) Ulcerative proctitis/ulcerative proctosigmoiditis (556.2/ 556.3) Left-sided ulcerative colitis (556.5) Pancolitis (556.6) Other ulcerative colitis/ulcerative colitis, unspecified (556.8) CD diagnosis in CU patients Patients not discharged within 5 year before index date Risk factors for surgery Anemia/hemorrage Drug exposure Aminosalicylic acid No Remote (>6 months) Recent (<= 6 months) Immunosuppressant No Remote (>6 months) Recent (<= 6 months)

14 Table S16: Rates and HR of abdominal surgery and infections among patients of UC treated with Infliximab versus those treated with Adalimumab. Intention to treat approach. Disease Outcome UC Events IFX ADA Crude HR Adjusted HR Rate (per 100 PY) Events Rate (per 100 PY) Estimate ICL ICU P Value Estimate ICL ICU P Value Surgery Infections IFX: Infliximab, ADA: Adalimumab, CD: Crohn sdisease, UC: Ulcerative colitis.py 100 person years. ICL / ICU: 95% lower / upper confidence limits.