Table 1.

Points to consider for the treatment of patients with immune mediated inflammatory diseases with Janus kinase (JAK) inhibitors

Item	Wording	LoE	SoR	Vote (%)	LoA
	General principles*
A	Initiation of JAK-inhibitor therapy and the treatment target to be achieved should be based on a shared decision between the patient and the medical specialist, which requires full information of the patient on the potential benefit and risks of this therapy.	n.a.	n.a.	100	10
B	Therapeutic approaches to treating patients with chronic inflammatory conditions should be in line with international and national recommendations (algorithms) for the management of the respective disease.	n.a.	n.a.	92	9.5
C	The points to consider when initiating JAK-inhibitor therapy do not provide information on when JAK-inhibitors should be used in the treatment algorithm, but rather attempt to assist the clinician once the decision to prescribe a JAK inhibitor has been made.	n.a.	n.a.	92	9.8
D	These points to consider address specific (but not all) aspects related to the application of JAK-inhibitor therapy and the clinician should additionally refer to the disease-specific product information.	n.a.	n.a.	88	9.8
	Individual points*
I	Indications
1	Patients with immune mediated inflammatory diseases (IMIDs) who have failed prior conventional and/or biological therapies; as of 2019, these include rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ulcerative colitis (UC).	1a	A	100	9.7
2	Currently, there is no direct evidence of superiority regarding efficacy or safety of one JAK-inhibitor over another one.	5	D	88	9.8
II	Treatment dose and comedications in different IMIDs
1	Use the dose recommended for the specific disease	1a	A	100	9.6
2	Consider dose adjustments in patients with higher age (>70 years), significantly impaired renal or hepatic function and/or risk of drug-interactions, or as a result of other comorbidities, as per individual product information.	2b/5	C/D	100	9.7
3	Regarding comedication, follow specific recommendations for the respective disease; in RA consider adding a JAK inhibitor to continued csDMARDs, if the patient tolerates the csDMARD	1a	A	92	9.1
4	Consider dose reduction of the JAK inhibitor in RA patients in sustained CDAI or Boolean remission on background csDMARDs.	1b	A	77	9
III	Contraindications (consult also label and warning, see general principle D)
1	Severe active (or chronic) infections, including TB and opportunistic infections.	2b/5	B/D	100	9.9
2	Current malignancies.	5	D	80	9.2
3	Severe organ dysfunction, such as severe hepatic disease (Child-Pugh C) or severe renal disease.	5	D	100	9.9
4	Pregnancy and lactation.	5	D	100	9.9
5	Recurrent VTE (unless anticoagulated)	5	D	93	8.8
IV	Pre-treatment screening and risks
1	Patient history and physical examination.	5	D	100	9.9
2	Routine laboratory testing (full and differential blood counts, liver tests (transaminases), renal function; lipid levels at approximately 3 months after initiation of therapy (and possibly at baseline unless measured within the last 12 months); no CPK testing recommended.	2b/5	B/D	80	9.3
3	Hepatitis B testing (hepatitis B surface antigen, hepatitis B surface antibody, hepatitis B core antibody, and with/without HBV DNA testing as discussed in text). Hepatitis C testing (hepatitis C antibody, with HCV RNA testing if antibody positive)	5	D	92	9.8
4	Human immunodeficiency virus testing in high-risk populations	5	D	100	9.9
5	TB screening as per national guidelines	2b	B	96	9.9
6	Assess and update vaccination status.	5	D	100	9.9
7	Consider risk factors for VTE, especially a past history of VTE.	5	D	96	9.9
V	Adverse events
1	Serious infections (similar to bDMARDs), opportunistic infections including TB, Herpes zoster* (increased rates compared to bDMARDs); the risk of infectious events can be lowered with reduction or elimination of concomitant glucocorticoid use.	2b	B	100	9.9
2	Rates of malignancy do not appear elevated with JAK inhibition, although the risk of NMSC may be elevated.	2b	B	95	9.6
3	Lymphopenia, thrombocytopenia, neutropenia, anaemia may occur.	2b	B	100	9.8
4	An increased risk of VTE has been reported in a safety trial of RA among patients using 10 mg two times a day tofacitinib and within the placebo-controlled trial period of baricitinib in patients with RA.	2b	B	94	9.5
5	Elevations of CPK are noted with JAK inhibitors but have not been associated with clinical events. Elevations of creatinine have been noted with JAK inhibitors but have not been associated with renal failure or hypertension.	2b	B	94	9.5
VI	Laboratory and clinical monitoring during follow-up.
1	Minimal laboratory monitoring: full and differential blood counts and liver transaminase tests at 1 and 3 months and then periodically, such as every 3 months; lipid levels only at month 3.	2b/5	B/D	92	9.4
2	Annual skin examination (for detection of skin cancer).	5	D	83	8.3
3	Evaluate response using validated, disease-specific measures of disease activity; for evaluation and definition of response, be aware that CRP and ESR may be reduced independently of reduction of disease activity and possibly even in infections.	2b/5	B/D	95	9.8

These bullet points have been agreed on as abbreviated summaries of the discussions and the explanatory text to each of these items should be regarded as an integral part of these points.

*These points are a short abbreviation of the items discussed and presented in detail in the body of the text. They should not be applied independently of the information provided there in more detail, but present only an overview of the general scope of the consensus statement. The percentages shown reflect the proportion of participants who approved the respective bullet point during the voting at the task force meeting. Some items carry two levels of evidence, because part of the respective points have only the level of expert opinion (level 5), namely II/2: comorbidities not studied, since most excluded from trials; III/1: patients with chronic infections (even if mild) were not studied; IV/2and VI/1: proposed intervals not studied; VI/3 blunting of the acute phase response during infections not sufficiently studied.

bDMARD, biological disease-modifying antirheumatic drug; CDAI, Crohn’s Disease Activity Index; CPK, creatine phosphokinase; CRP, C reactive protein; csDMARD, conventional synthetic disease-modifying antirheumatic drug; HBV, hepatitis B virus; HCV, hepatitis C virus; LoA, levels of agreement; LoE, level of evidence; n.a., not available; NMSC, non-melanoma skin cancer; SoR, strength of recommendation; TB, tuberculosis; VTE, venous thromboembolism.