Table 1.
Efficacy and safety data reported by select comorbidities in patients treated with baricitinib or placebo*
| Depression | No depression | Osteoporosis | No osteoporosis | Hepatic disorders | No hepatic disorders | CV disorders | No CV disorders | Pulmonary disorders | No pulmonary disorders | Overall | |
| Baricitinib 4 mg | |||||||||||
| Efficacy outcomes at week 12 | |||||||||||
| Patients, N | 64 | 739 | 113 | 690 | 222 | 581 | 350 | 453 | 77 | 726 | 803 |
| ACR20 response (%)† | 59.4 | 68.2 | 65.5 | 67.8 | 67.1 | 67.6 | 68.3 | 66.9 | 66.2 | 67.6 | 67.5 |
| ACR50 response (%)† | 34.4 | 41.7 | 40.7 | 41.2 | 40.5 | 41.3 | 40.9 | 41.3 | 40.3 | 41.2 | 41.1 |
| DAS 28-hsCRP ≤3.2 response (%)† | 31.3 | 44.9 | 46.9 | 43.3 | 42.8 | 44.2 | 44.9 | 43.0 | 37.7 | 44.5 | 43.8 |
| Change in HAQ-DI‡ | −0.46 | −0.54 | −0.36 | −0.55 | −0.58 | −0.53 | −0.54 | −0.52 | −0.51 | −0.53 | −0.53 |
| Safety outcomes at week 16 | |||||||||||
| Patients, N | 64 | 738 | 113 | 689 | 222 | 580 | 350 | 452 | 77 | 725 | 802 |
| Any TEAE, n (%), (EAIR) | 45 (70.3), (246) |
450 (61.0), (208) |
70 (61.9), (216) |
425 (61.7), (210) |
152 (68.5), (232) |
343 (59.1), (202) |
227 (64.9), (221) |
268 (59.3), (202) |
62 (80.5), (284) |
433 (59.7), (203) |
495 (61.7), (210) |
| SAE, n (%), (EAIR) | 0, (0.0) |
25 (3.4), (11.5) |
9 (8.0), (27.8) |
16 (2.3), (7.9) |
8 (3.6), (12.2) |
17 (2.9), (10.0) |
14 (4.0), (13.6) |
11 (2.4), (8.3) |
4 (5.2), (18.3) |
21 (2.9), (9.8) |
25 (3.1), (10.6) |
| Discontinuation due to AEs, n (%), (EAIR) | 1 (1.6), (5.5) |
24 (3.3), (11.1) |
7 (6.2), (21.6) |
18 (2.6), (8.9) |
9 (4.1), (13.7) |
16 (2.8), (9.4) |
14 (4.0), (13.6) |
11 (2.4), (8.3) |
3 (3.9), (13.8) |
22 (3.0), (10.3) |
25 (3.1), (10.6) |
| Deaths, n (%), (EAIR) | 0, (0.0) |
0, (0.0) |
0, (0.0) |
0, (0.0) |
0, (0.0) |
0, (0.0) |
0, (0.0) |
0, (0.0) |
0, (0.0) |
0, (0.0) |
0, (0.0) |
| Placebo | |||||||||||
| Patients, N | 69 | 812 | 134 | 747 | 202 | 679 | 381 | 500 | 89 | 792 | 881 |
| Efficacy outcomes at week 12 | |||||||||||
| ACR20 response (%)† | 31.9 | 39.8 | 32.1 | 40.4 | 37.1 | 39.8 | 40.7 | 38.0 | 32.6 | 39.9 | 39.2 |
| ACR50 response (%)† | 8.7 | 14.9 | 11.9 | 14.9 | 11.4 | 15.3 | 14.4 | 14.4 | 12.4 | 14.6 | 14.4 |
| DAS 28-hsCRP ≤3.2 response (%)† | 13.0 | 16.9 | 12.7 | 17.3 | 12.9 | 17.7 | 15.7 | 17.2 | 16.9 | 16.5 | 16.6 |
| Change in HAQ-DI§ | −0.20 | −0.26 | −0.08 | −0.27 | −0.28 | −0.26 | −0.27 | −0.23 | −0.17 | −0.26 | −0.25 |
| Safety outcomes at week 16 | |||||||||||
| Any TEAE, n (%), (EAIR) | 57 (82.6), (301) |
437 (53.8), (192) |
91 (67.9), (251) |
403 (53.9), (191) |
119 (58.9), (207) |
375 (55.2), (198) |
228 (59.8), (212) |
266 (53.2), (191) |
59 (66.3), (238) |
435 (54.9), (196) |
494 (56.1), (200) |
| SAE, n (%), (EAIR) |
6 (8.7), (31.7) |
25 (3.1), (11.0) |
9 (6.7), (24.9) |
22 (2.9), (10.4) |
5 (2.5), (8.7) |
26 (3.8), (13.7) |
16 (4.2), (14.9) |
15 (3.0), (10.8) |
2 (2.2), (8.1) |
29 (3.7), (13.1) |
31 (3.5), (12.6) |
| Discontinuation due to AEs, n (%), (EAIR) | 3 (4.3), (15.9) |
21 (2.6), (9.2) |
9 (6.7), (24.9) |
15 (2.0), (7.1) |
6 (3.0), (10.4) |
18 (2.7), (9.5) |
12 (3.1), (11.1) |
12 (2.4), (8.6) |
4 (4.5), (16.1) |
20 (2.5), (9.0) |
24 (2.7), (9.7) |
| Deaths, n (%), (EAIR) | 1 (1.4), (5.3) |
0, (0.0) |
1 (0.7), (2.8) |
0, (0.0) |
0, (0.0) |
1 (0.1), (0.5) |
1 (0.3), (0.9) |
0, (0.0) |
0, (0.0) |
1 (0.1), (0.5) |
1 (0.1)§, (0.4) |
| Baricitinib safety outcomes after median exposure of 2 years | |||||||||||
| Patients, N | 342 | 3097 | 500 | 2939 | 810 | 2629 | 1535 | 1904 | 373 | 3066 | 3439 |
| Any TEAE, n (%), (EAIR) | 318 (93.0), (51.4) |
2592 (83.7), (43.1) |
444 (88.8), (45.9) |
2466 (83.9), (43.5) |
711 (87.8), (45.1) |
2199 (83.6), (43.5) |
1351 (88.0), (44.8) |
1559 (81.9), (43.1) |
343 (92.0), (45.7) |
2567 (83.7), (43.6) |
2910 (84.6), (43.9) |
| SAE, n (%), (EAIR) | 73 (21.3), (11.8) |
489 (15.8), (8.1) |
132 (26.4), (13.7) |
430 (14.6), (7.6) |
168 (20.7), (10.7) |
394 (15.0), (7.8) |
348 (22.7), (11.5) |
214 (11.2), (5.9) |
102 (27.3), (13.6) |
460 (15.0), (7.8) |
562 (16.3), (8.5) |
| Discontinuation due to AEs, n (%), (EAIR) | 36 (10.5), (5.8) |
283 (9.1), (4.7) |
71 (14.2), (7.3) |
248 (8.4), (4.4) |
93 (11.5), (5.9) |
226 (8.6), (4.5) |
173 (11.3), (5.7) |
146 (7.7), (4.0) |
35 (9.4), (4.7) |
284 (9.3), (4.8) |
319 (9.3), (4.8) |
| Deaths, n (%), (EAIR) | 3 (0.9), (0.5) |
10 (0.3), (0.2) |
7 (1.4), (0.7) |
6 (0.2), (0.1) |
1 (0.1), (0.1) |
12 (0.5), (0.2) |
9 (0.6), (0.3) |
4 (0.2), (0.1) |
4 (1.0), (0.5) |
9 (0.3), (0.2) |
13 (0.4), (0.2) |
Comorbidities and associated terms are based on the Medical Dictionary for Regulatory Activities classification system. Terms for depression included depressed mood, depression postoperative, depression, depressive symptoms, dysthymic disorder, major depression, suicidal ideation and suicide attempt. Terms for osteoporosis included low bone density (bone density decreased), non-traumatic bone fracture (osteoporotic fracture), osteopaenia, osteoporosis postmenopausal, osteoporosis and senile osteoporosis. Terms for hepatic disorders included alanine aminotransferase increased, aspartate aminotransferase increased, biliary cirrhosis primary, blood alkaline phosphatase increased, cholestasis, chronic hepatitis, drug-induced liver injury, gamma-glutamyltransferase increased, hepatic enzyme abnormal, hepatic enzyme increased, hepatic function abnormal, hepatic lesion, hepatic steatosis, hepatitis, hepatitis acute, hepatitis toxic, hepatomegaly, hypertransaminasaemia, hypoalbuminaemia, jaundice, liver disorder, liver function test abnormal, liver injury, liver operation, non-alcoholic steatohepatitis, serum hepatitis B virus core antibody positive, serum hepatitis B virus surface antibody positive, spider nevus, transaminases increased and varices oesophageal. Terms for cardiovascular disorders included acute myocardial infarction, blood cholesterol increased, blood glucose abnormal, blood glucose increased, cerebral infarction, cerebrovascular accident, coronary artery bypass, diabetes mellitus, diabetes mellitus inadequate control, diabetic ketoacidosis, essential hypertension, gestational diabetes, glucose tolerance impaired, hypercholesterolaemia, hyperglycaemia, hyperlipidaemia, hypertension, hypertensive cardiomyopathy, hypertensive heart disease, intermittent claudication, ischaemic stroke, labile hypertension, lacunar infarction, low-density lipoprotein increased, myocardial infarction, peripheral arterial occlusive disease, peripheral artery stenosis, subarachnoid haemorrhage, subdural haematoma, systolic hypertension and transient ischaemic attack. Terms for pulmonary disorders included allergic bronchitis, apnoea, asbestosis, aspirin-exacerbated respiratory disease, asthma, asthma exercise-induced, atelectasis, bronchial hyper-reactivity, bronchiectasis, bronchiolitis, bronchitis chronic, bronchospasm, bullous lung disease, chronic obstructive pulmonary disease, cor pulmonale chronic, diffuse panbronchiolitis, dyspnoea, dyspnoea exertional, emphysema, idiopathic pulmonary disease, infantile asthma, interstitial lung disease, Langerhans cell histiocytosis, lung consolidation, lung cyst, obstructive airways disorder, pneumoconiosis, pneumonitis, pulmonary bulla and pulmonary fibrosis. The number of patients with idiopathic pulmonary disease, interstitial lung disease or pulmonary fibrosis was low (6 and 8 patients for baricitinib 4 mg and placebo, respectively); thus, the impact of these conditions on baricitinib treatment outcomes cannot be concluded with certainty.
*Efficacy outcomes were assessed at week 12 for baricitinib and placebo; safety outcomes were recorded from baseline to week 16 for baricitinib and placeboin the randomised controlled trials and for all patients receiving baricitinib after a median exposure of 2 years in the long-term extension study.
†Percentage of patients achieving ACR20, ACR50 and DAS 28-hsCRP ≤3.2.
‡Least squares mean changes in HAQ-DI scores from baseline to week 12; negative changes indicate improvement from baseline.
§One death occurred in a patient receiving placebo; this patient had depression, osteoporosis and a cardiovascular disorder.
ACR, American College of Rheumatology;ACR20, 20% improvement from baseline in ACR criteria;ACR50, 50% improvement from baseline in ACR criteria;AE, adverse event;CV, cardiovascular;DAS28-hsCRP, Disease Activity Score for 28-joints based on the level of high-sensitivity C reactive protein;EAIR, exposure-adjusted incidence rate;HAQ-DI, Health Assessment Questionnaire–Disability Index;N, number of patients randomised and treated in each comorbidity subgroup; n, number of patients with event; SAE, serious adverse event;TEAE, treatment-emergent adverse event.