Table 1.
Studies assessing the value of biomarkers in predicting response to thiopurine treatment in IBD.
| Study | Patient population | Subjects (n) | Therapy | Metabolite/Biomarker | Cut off level |
Hazard Ratio Odds Ratio or P-value |
Sensitivity/Specificity (%) | PPV/NPV (%) | Definition of relapse | Definition of response |
|---|---|---|---|---|---|---|---|---|---|---|
| Park et al. (47) | CD Pediatric/Adult |
82 | AZA/6-MP | CRP | ≥5 mg/L | p = 0.009 | – | – | CDAI > 150 | CDAI < 150 (remission) |
| Lémann et al. (48) | CD Adult |
83 | AZA | CRP Hb |
≥20 mg/L <12 g/dL |
p = 0.0002 p = 0.043 |
– | – | CDAI > 250 OR CDAI between 150 and 250 on 3 consecutive weeks with an increase of at least 75 points above baseline OR the need for surgery for CD (with the exception of limited perianal surgery) |
– |
| Treton et al. (49) | CD Adult |
66 | AZA | CRP Hb NC |
≥20 mg/L <12 g/dl >4 × 109/l |
HR 58.6, p = 0.002 HR 4.8, p = 0.04 HR 3.2, p = 0.003 |
– | – | HBI ≥ 4 with the need for treatment | HBI ≤ 3 without any steroid treatment or immunosuppressive agent in the past 3 months and without surgery. |
| Osterman et al. (50) | CD/UC Adult |
971 | AZA/6-MP | 6-TGN | ≥230 pmol/8 × 108 RBCs | OR = 3.27 | 62/67 | – | Not provided | Not provided |
| Nguyen et al. (51) | CD/UC Pediatric |
86 | AZA | 6-TGN | ≥250 pmol/8 × 108 RBCs | OR = 4.4 p = 0.007 |
– | – | Inability to achieve steroid free remission | PCDAI ≤ 10 without corticosteroids PUCAI ≤ 10 without corticosteroids |
| Kwan et al. (52) | CD/UC Adult |
39 | AZA/6-MP | 6-TGN | ≥230 pmol/8 × 108 RBCs | – | 63/67 | 63/67 | Disease flare requiring cyclosporine, infliximab, intravenous corticosteroid | Any reduction in oral steroid use, HBI, SCCAI scores, and clinical assessment |
| Gonzalez-Lama et al. (53)a | CD/UC Adult |
113 | AZA/6-MP | 6-TGN | ≥230 pmol/8 × 108 RBCs | – | 41/56 at 2 weeks 58/50 at 1 month 57/50 at 2 months 68/62 at 4 months |
61/36 at 2 weeks 64/44 at 1 month 67/40 at 2 months 84/40 at 4 months |
Unable to achieve steroid free CDAI <150 | CDAI <150 or mTWAI <11 without corticosteroids for at least 6 months |
| Gonzalez-Lama et al. (53)b | CD/UC Adult |
113 | AZA/6-MP | 6-TGN | 260 pmol/8 × 108 RBCs | – | 35/65 at 2 weeks 49/53 at 1 month 53/57 at 2 months 57/75 at 4 months |
63/37 2 weeks 62/40 1 month 68/41 2 months 87/37 4 months |
Unable to achieve steroid free CDAI <150 | CDAI <150 or mTWAI <11 without corticosteroids for at least 6 months |
| Waljee et al. (54) | CD/UC Adult |
346 | AZA/6-MP | 6-TGN | – | AuROC = 0.594 | – | – | mHBI ≥ 4 on or off steroids or; mHBI <4 requiring steroids | CD—mHBI <4, steroid free, no fistulae for 3 weeks UC—mUCDAI <4 off steroids |
| Nakarai et al. (55) | UC Adult |
158 | AZA/6-MP Biologics |
fHb | <100 ng/mL | – | 92/71 | 37/97 | – | MS = 0 |
| Mooiweer et al. (56) | CD/UC Adult |
164 | AZA/6-MP Biologics |
fHb | 1.5 μg/g | – | 74/84 | 72/84 | – | Assessed ability to predict MS |
| Takashima et al. (57) | UC Pediatric/Adult |
98 | AZA/6MP Biologics |
FIT fCP |
<100 ng/mL <250 μg/g |
– | 95/62 82/62 |
– | – | Assessed ability to predict MES |
AuROC, Area under Receiver Operator Characteristic Curve; AZA, Azathioprine; CD, Crohn's Disease; CDAI, Crohn's Disease Activity Index; CRP, C-Reactive Protein; fCP, fecal calprotectin; fHb, fecal Hemoglobin; FIT, fecal immunochemical tests; Hb, hemoglobin; HBI, Harvey-Bradshaw Index; mHBI, modified Harvey-Bradshaw Index; MES, Mayo endoscopic subscore; MS, Mayo Score; mTWAI, modified Truelove-Witts Activity Index; mUCDAI, modified Ulcerative Colitis Disease Activity Index; NC, neutrophil count; PUCAI, Pediatric Ulcerative Colitis Activity Index; PPV/NPV; negative/positive predictive value; RBCs, Red Blood Cells; SCCAI, Simple Clinical Colitis Activity Index; UC, Ulcerative Colitis; 6-MP, 6-Mercaptopurine; 6-TGN, 6-Thioguanine nucleotides. Gonzalez-Lama et al. (53) tested two different cut-off levels in the same study indicated by the superscript letters a and b.