Table 4.

Adverse effects in patients with IBD receiving Janus kinase inhibitors; real-world data

Study	Number of patients/reports	Distribution by Indication	Drug(s)	Exposure (mean in years)	AEs reported
Burmester et al. [40]	13,567	RA = 7964 PsA = 783 UC = 1157 PsA = 3663	Tofacitinib	RA = 2.1 PsA = 3.0 UC = 1.7 PsO = 2.4	AEs: IRs were highest for HZ in all groups
					SAEs: IRs (95% CI) were highest in RA 9.0 (8.6 to 9.4) vs 7.0 (5.8–8.2) for PsA, 8.5 (7.4–9.8) for UC, and 5.5 (5.0–6.0) for PsO
					Mortality: Age-adjusted and sex adjusted mortality ratios were ≤0.2 across cohorts. The IR for mortality was 0.1 (95% CI 0.0 to 0.3)
					Infections: The 3 more frequent infections were pneumonia, HZ, urinary tract infection
					Malignancies: IRs for all malignancies (excluding NMSC) were ≤0.1 for RA and PsA and highest with UC
Olivera et al. [44]	66,159 (MA)	UC/CD = 2077 RA = 10,706, AS = 214 PsO = 2210	Tofacitinib Filgotinib, Baricitinib Upadacitinib	8.7	AEs: Mean IR of AES was 42.69 per 100 PYE
					SAEs: Mean IR of SAES was 9.98 per 100 PYE
					Mortality: Relative risk vs patients receiving placebo or active comparator: 0.72 (95% CI 0.40–1.28)
					Infections: IR serious infection was 2.81 per 100 PYE. More risk HZ
					Malignancies: IR of NMSC was 0.51 per 100 PYE IR (excluding NMSC) was 0.75 per 100 PYE
Rubin et al. [47]	4226 reports	UC = 8916	Tofacitinib	2.2	AEs: 12,103 cases. The most reported was drug ineffectiveness (18.5%)
					SAEs: 1141 (27%). Of 18 fatal cases, 3 were related to tofacitinib
					Infections: 6.8% reported infections, of which 292 were serious The most frequent were nasopharyngitis and HZ
					Malignancies: 52 cases (1.2%) reported 56 neoplasms
Winthrop et al. [63]	3691	RA = 3691	Filgotinib	5.6	AEs: The most common were nasopharyngitis, upper respiratory tract infection and nausea
					SAEs: 5 patients reported a MACE. Patients who had MI or stroke all had ≥ 1 CV risk factor. Was observed 0.5 per 100 PYE (200 mg) vs 0.3 per 100 PYE (100 mg) and appeared to remain stable over time. All fatal and MI strokes occurred in patients with ≥1 CV risk factor
					Infections: Six SAEs of HZ were reported by 5 patients receiving filgotinib 200 mg and one receiving filgotinib 100 mg with 0.6 and 0.9 per 100 PYE for filgotinib 200 and 100 mg, respectively
					Malignancies: During the placebo-controlled period, one malignancy each was reported with filgotinib 100 mg (cervix carcinoma) and placebo (malignant glioma) Long term, of all non-NMSC malignancies for filgotinib 200 and 100 mg remained stable over time
Hoisnard et al. [84]	126,815 reports	Not reported	Tofacitinib Ruxolitinib Baricitinib	No data	AEs: Overall, 376,487 AEs were reported in the 126,815 safety reports
					SAEs: MACE and cerebrovascular events were not reported. Embolism and thrombosis were observed in 1803 patients (1.4%)
					Infections: The most frequently reported infections were viral: 3.3% HZ, 1.8% influenza (1.8%) and pneumocystis infections
					Malignancies: Hematopoietic neoplasms (excluding leukemias and lymphomas), skin neoplasm, and leukemias were the most reported neoplasms (0.65, 0.78 and 0.66%, respectively)

AE adverse event, CV cardiovascular, PsA psoriatic arthritis, HZ herpes zoster, IBD inflammatory bowel disease, IR incidence rate, MA meta-analysis, MACE major cardiovascular event, MI myocardial infarction, NMSC non-melanoma skin cancer, PsA psoriatic arthritis, PsO psoriasis, PYE patient years, RA rheumatoid arthritis, RR relative risk, SAE serious adverse event, UC ulcerative colitis