Immune-mediated diseases and thromboembolic events: a modified Delphi panel

Figures & data

Figure 1. Utilization of treatment modalities (n = 13).

Figure 2. Ulcerative colitis and Crohn’s disease: characterizing high-risk patients and altering clinical approach. Abbreviations. TE, thromboembolic event; CRP, C-reactive protein; GI, gastrointestinal; VTE, venous thromboembolism; PCP, primary care providers.

Figure 3. Systemic lupus erythematosus and rheumatoid arthritis. Abbreviations. VTE, venous thromboembolism; RA, rheumatoid arthritis; BMI, body mass index; HRT, hormone therapy; PAH, pulmonary arterial hypertension; TE, thromboembolic event; SLE, systemic lupus erythematosus.

Figure 4. Treatment modalities that require closer evaluation in light of TE risk. Abbreviations. TE, thromboembolic event; RA, rheumatoid arthritis.

Table 1. Results from proposed consensus statement questionnaire.

	N = 12 (sensitivity analysis excluding outlier)
Proposed consensus statement	Mean	SD	% Agreement (Agree or Slightly Agree)
Autoimmune disease patient populations (categorically aggregated)	4.85		98.0%
1. Patients with autoimmune diseases are associated with a higher risk of TE relative to the general population.	5	0	100.0%
2. Among patients with autoimmune diseases, patients with Lupus and RA carry the highest risk of TE.	4.67	0.89	91.7%
3. Patients with inflammatory bowel diseases UC or CD are associated with an increased risk of TE.	4.75	0.45	100.0%
4. Optimal management of patients with autoimmune diseases in these populations (Lupus/RA/IBD) should involve efforts to reduce the overall TE risk	4.75	0.62	91.7%
5. In addition to the inherent risk of TEs in the autoimmune disease patient populations, there are additional risk factors that further increase TE risk – some modifiable and other non-modifiable.	5	0	100.0%
6. When patients with autoimmune diseases at risk for TEs carry non-modifiable and/or modifiable risk factors, the risk of TEs incrementally increases.	4.75	0.45	100.0%
7. The multidisciplinary physician community treating autoimmune disease patients should have increased awareness of TE risk, including the potential impact of modifiable and non-modifiable risk factors that further increase the risk of TE.	5	0	100.0%
Non-modifiable risk factors
8. Patients with autoimmune diseases at risk of TEs may have non-modifiable TE risk factors that further increase TE risk such as age, a prior clotting event, recent surgery or hospitalization, limited mobility, bleeding risk, and a history of miscarriage that should be considered when making treatment decisions.	5	0	100.0%
Modifiable risk factors: categorically aggregated	4.82		98.0%
9. Physicians should encourage autoimmune disease patients to make lifestyle changes if they carry modifiable risk factors including smoking, obesity, and sedentary lifestyle.	5	0	100.0%
10. When considering treatment options for treating autoimmune disease patients at risk of TEs, physicians should assess all potential modifiable risk factors that may increase the risk of TEs, including medications.	4.83	0.39	100.0%
11. Certain classes of medications have been associated with increased risk of TEs including corticosteroids, oral contraceptives or hormone replacement therapy, and JAK inhibitors.	4.83	0.39	100.0%
12. Rheumatoid arthritis patients treated with tofacitinib 10 mg BID were observed to have an increased incidence of TEs.	4.83	0.39	100.0%
13. In order to minimize the risk of TEs in patients with autoimmune diseases, physicians should exercise caution when prescribing medications that have been associated with increased risk of TEs including corticosteroids, oral contraceptives or hormone replacement therapy, and JAK inhibitors.	4.75	0.87	92.7%
14. Despite a potential increase in TE risk, JAK inhibitors remain a viable option for autoimmune disease patients and have a role in treatment algorithms, especially amongst those who have exhausted other options.	5	0	100.0%
15. The use of tofacitinib may incrementally increase the risk of TEs in autoimmune disease patients that carry other TE risk factors including high BMI, sedentary lifestyle, and other medications such as corticosteroids, oral contraceptives or hormone replacement therapy.	4.67	0.65	91.7%
16. Based on the recent FDA and EMA approvals of the selective JAK-1 inhibitor upadacitinib for the treatment of rheumatoid arthritis patients, the risk of TEs are viewed by regulatory authorities as a class-effect for all JAK inhibitors.	4.67	0.48	100.0%

Abbreviations. TE, thromboembolic event; RA, rheumatoid arthritis; UC, ulcerative colitis; CD, Crohn’s disease; IBD, inflammatory bowel diseases; BMI, body mass index.