European Delphi panel to build consensus on tapering and discontinuing thrombopoietin receptor agonists in immune thrombocytopenia

Figures & data

Figure 1. Modified Delphi framework.

*130 indicates the total number of statements over the three survey rounds.

Table I. Consensus statements framework.

Domain	Subdomain
Selection of patients	General considerations for selecting patients The patient’s age The patient’s response to TPO-RAs Duration of treatment Platelet count Bleeding and hemorrhage history The patient’s perspective and involvement in decision-making
Tapering strategies and monitoring approaches	Eltrombopag discontinuation regimen Romiplostim discontinuation regimen Duration of tapering Monitoring of patient during tapering Management of platelet count drop during tapering Definition of relapse Failure of discontinuation Predictors for successful tapering and discontinuation
Post discontinuation	Definition and conditions for sustained response off treatment (SRoT)

Table II. Analysis rules.

Rule 1: Questions that show variable response patterns (≤40%) spread across response options in a non-skewed way will be removed.

Rule 2: Questions with responses between 41% and 79% will be re-asked with three response options: disagree, neutral, agree.

Rule 3: Questions that showed a skewed response pattern, with a majority of responses (≥80%) spread across 5 or 3 options, will be summed and presented back with a binary response option: agree or disagree.

Rule 4: Three-point Likert scale questions in the second round with responses between 41% and 79% will be re-asked on a three-point Likert scale in Round 3.

Rule 5: Binary and three-point Likert scale questions that showed a response pattern of ≥80% agreement will be considered consensus; a response pattern of ≥80% disagreement will be considered dissensus.

Table III. Summary of survey topics that achieved consensus or dissensus.

Consensus
Selection of patients Tapering and discontinuing TPO-RAs is appropriate in stable patients with ITP who maintained a platelet count above 100 × 10^9/L for a minimum of six months. There is no dose of TPO-RAs above which tapering and discontinuation cannot be considered. Tapering can be considered for patients who have achieved a stable response to treatment in approximately 6 months. Tapering could be considered for patients that have achieved and maintained a safe platelet count for at least 6 months or less (2–3 months) for patients with platelet count above 100 × 10^9/L. Patient’s involvement in the decision to attempt tapering and discontinuation: Relevance of assessing patient’s motivation and desire to discontinue prior to attempting tapering and discontinuation Tapering strategies and monitoring approaches Discontinuation regimen for eltrombopag (Table IV) Discontinuation regimen for romiplostim (Table IV) TPO-RAs should be tapered for 2–3 months, longer in some circumstances, provided that the clinical response in maintained, prior to discontinuing. Monitoring intervals during tapering should not be longer than 4 weeks. The minimum dose of the same TPO-RAs should be reintroduced if a patient experiences any bleeding event and with less than 50% drop in platelet count. A patient can be considered in relapse when their platelet count drops below 30 × 10^9/L. Patient’s platelet count prior tapering and discontinuation is the only known predictor of successful discontinuation. Post discontinuation Definition of sustained response off treatment: A patient who is not receiving anticoagulants can be considered in sustained response off treatment if, after discontinuation, they keep having a positive response off treatment (platelet count is more than 50 × 10^9/L) for at least 3 months.
Dissensus
Selection of patients Patients above 40 years of age are ineligible for tapering and discontinuation. Patients who have achieved a stable response to treatment in less than 1 month are eligible for tapering and discontinuation. Patients who have achieved a stable mean platelet count with TPO-RA treatment above 30 × 10^9/L and are receiving anticoagulants or antiplatelets are eligible for tapering and discontinuation. Patients with an adequate, normal or above normal platelet count and a history of minor bleedings are ineligible for tapering and discontinuation.

Table IV. Tapering regimens that achieved consensus for eltrombopag and romiplostim.

Eltrombopag	Romiplostim
Taper the dose of eltrombopag by 25 mg every 2 weeks down to a minimum dose of 25 mg. Administer 25 mg every other day for 2 weeks, then discontinue.	Taper the dose of romiplostim of 1 mcg/kg/week every 2 weeks until a dose of 1 mcg/kg/week is reached and: (Regimen 1) administer a 1 mcg/kg dose once every other week before discontinuing treatment. (Regimen 2) administer 1 mcg/kg dose every other week for 2 or 3 administrations, before discontinuing treatment. (Regimen 3) taper down until a dose of 0.5mcg/kg/week is reached, then discontinue.