What is real-world evidence?

RWE can be derived from several different sources; these can include:1

  • Electronic Health Records
    • Chart review or manual data extraction
    • Technology-enabled abstraction

  • Claims Systems
    • Claims data from billing 

  • Cancer Registries
    • Retrospective data
    • Prospective data
  • Patient Reported Data
    • Patient health surveys or questionnaires
    • Sourced from patients directly (eg., wearable devices)

  • Genomic databases
    • Genome sequencing linked with real-world clinical data to create a clinico-genomic database
Diagram showing sources of real-world evidence (RWE): Infographic illustrating sources of real-world evidence, including expanded access programmes, registries, electronic health records, medical claims, health surveys, and patient applications.

Strengths and limitations of RCTs4

Table summarising the strengths and limitations of randomised controlled trials (RCTs). Strengths include strong internal validity, randomisation, control groups, prespecified endpoints, and blinding. Limitations include limited generalisability, unrepresentative patient populations, use of surrogate endpoints, time and resource requirements, and the inability to consistently capture, late, long-term and patient centred outcomes.

Strengths and limitations of RWE4

Table summarising the strengths and limitations of real-world evidence (RWE). Strengths include strong external validity and generalisability, representative patient populations, the ability to evaluate topics that are difficult to randomise, and lower time and resource requirements. Limitations include a higher risk of bias, lack of randomisation and control groups, and the fact that RWEs are often retrospective and cannot be blinded.

RWE investigates the performance of an intervention under real-world conditions.7

RWE can complement clinical data in several ways, including:

  • Providing insights into patient characteristics, treatment outcomes and treatment practices in the real-world setting6,8,9
  • Providing additional insights in evidence sometimes not addressed by RCTs, such as:
    • Long-term effectiveness and safety data9
    • Treatment outcomes in typically under-represented MM patient populations2-6
Figure outlining why real-world evidence (RWE) is important. The figure highlights that data generated through RWE can support for expansion of clinical labels, enable new medical applications, and inform changes to clinical guidelines or treatment practices.

Ixazomib FAQs

What is Ixazomib?

Ixazomib is an oral, highly selective and reversible proteasome inhibitor. Each capsule of Ixazomib contains Ixazomib citrate, a prodrug that rapidly hydrolyses under physiological conditions to its biologically active form, Ixazomib.

1. Ixazomib. Summary of Product Characteristics.

What is the licensed indication for Ixazomib?

Ixazomib in combination with lenalidomide and dexamethasone is indicated for the treatment of adult patients with multiple myeloma who have received at least one prior therapy.1

1. Ixazomib. Summary of Product Characteristics.

Where is Ixazomib reimbursed?

In England, IRd is recommended by NICE as an option for treating multiple myeloma in adults if they have already had two or three previous lines of therapy and the company provides Ixazomib according to the commercial arrangement.1 Ixazomib is also available to appropriate patients in Wales and Northern Ireland.2

1. NICE. Ixazomib with lenalidomide and dexamethasone for treating relapsed or refractory multiple myeloma. Available from www.nice.org.uk/guidance/TA870. Accessed March 2026

2. All Wales Therapeutics and Toxicology Centre. Ixazomib citrate. Available at: https://awttc.nhs.wales/accessing-medicines/medicine-recommendations/Ixazomib-citrate-ninlaro.

How does Ixazomib work?  

Ixazomib preferentially binds and inhibits the chymotrypsin-like activity of the beta 5 subunit of the 20S proteasome.Ixazomib induced apoptosis of several tumour cell types in vitro. Ixazomib demonstrated in vitro cytotoxicity against myeloma cells from patients who had relapsed after multiple prior therapies, including bortezomib, lenalidomide, and dexamethasone.1 The combination of Ixazomib and lenalidomide demonstrated synergistic cytotoxic effects in multiple myeloma cell lines. In vivo, Ixazomib demonstrated antitumour activity in various tumour xenograft models, including models of multiple myeloma. In vitro, Ixazomib affected cell types found in the bone marrow microenvironment including vascular endothelial cells, osteoclasts and osteoblasts.

1. Ixazomib. Summary of Product Characteristics.

What is the recommended Ixazomib dose and how is it administered?

Ixazomib should be taken in combination with lenalidomide and dexamethasone.1

  • The recommended starting dose of Ixazomib is 4 mg administered orally on Days 1, 8, and 15 of a 28-day treatment cycle. Ixazomib should be swallowed whole with water at least 1 hour before or at least 2 hours after food

  • The recommended starting dose of lenalidomide is 25 mg administered daily on Days 1 to 21 of a 28-day treatment cycle

  • The recommended starting dose of dexamethasone is 40 mg administered on Days 1, 8, 15, and 22 of a 28-day treatment cycle

Prior to initiating a new cycle of therapy:1

  • Absolute neutrophil count should be ≥1000/mm3

  • Platelet count should be ≥75000/mm3
  • Non‑haematologic toxicities should, at the physician’s discretion, generally be recovered to patient’s baseline condition or ≤Grade 1

Antiviral prophylaxis should be considered in patients being treated with Ixazomib to decrease the risk of herpes zoster reactivation. Patients included in studies with Ixazomib who received antiviral prophylaxis had a lower incidence of herpes zoster infection compared to patients who did not receive prophylaxis.1

Thromboprophylaxis is recommended in patients being treated with Ixazomib in combination with lenalidomide and dexamethasone, and should be based on an assessment of the patient's underlying risks and clinical status.1

Ixazomib should be taken at approximately the same time on Days 1, 8, and 15 of each treatment cycle at least 1 hour before or at least 2 hours after food.1 The capsule should be swallowed whole with water. It should not be crushed, chewed, or opened.1

Treatment should be continued until disease progression or unacceptable toxicity.1 Treatment with Ixazomib in combination with lenalidomide and dexamethasone for longer than 24 cycles should be based on an individual benefit risk assessment, as the data on the tolerability and toxicity beyond 24 cycles are limited.1

Refer to the Ixazomib SmPC for full dosing guidelines.

1. Ixazomib. Summary of Product Characteristics.

How should the dosing be adjusted in special populations?
  • No dose adjustment of Ixazomib is required for patients over 65 years of age
  • No dose adjustment of Ixazomib is required for patients with mild hepatic impairment (total bilirubin ≤ upper limit of normal (ULN) and aspartate aminotransferase (AST) > ULN or total bilirubin > 1-1.5 x ULN and any AST). The reduced dose of 3 mg is recommended in patients with moderate (total bilirubin > 1.5-3 x ULN) or severe (total bilirubin > 3 x ULN) hepatic impairment
  • No dose adjustment of Ixazomib is required for patients with mild or moderate renal impairment (creatinine clearance ≥ 30 mL/min). The reduced dose of 3 mg is recommended in patients with severe renal impairment (creatinine clearance < 30 mL/min) or end-stage renal disease (ESRD) requiring dialysis. Ixazomib is not dialyzable and, therefore, can be administered without regard to the timing of dialysis
  • The safety and efficacy of Ixazomib in children below 18 years of age have not been established. No data are available

Refer to the Ixazomib SmPC for the full dose modification guidelines. Refer to the Ixazomib SmPC for an overview of all Ixazomib side effects. For additional information regarding lenalidomide or dexamethasone, please refer to each respective SmPC.

1. Ixazomib. Summary of Product Characteristics.

What are the most common side effects of IRd?

Clinical studies have shown the most frequently reported adverse reactions (≥ 20%) in 418 patients treated with IRd to be diarrhoea (47%), thrombocytopenia (41%), neutropenia (37%), constipation (31%), upper respiratory tract infection (28%), peripheral neuropathy (28%), nausea (28%), back pain (25%), rash (25%), peripheral oedema (24%), vomiting (23%) and bronchitis (20%). Serious adverse reactions reported in ≥ 2% of patients included diarrhoea (3%), thrombocytopenia (2%) and bronchitis (2%).1

Please refer to the SmPC for further information on the Ixazomib tolerability profile.

1. Ixazomib. Summary of Product Characteristics.

A healthcare professional wearing a white coat and stethoscope is seated at a desk, holding a clipboard and pen while speaking with another person across the table in a bright clinical setting.

If you have any questions or would like more information about Ixazomib, click below to request a meeting with one of our Takeda representatives.

MM, multiple myeloma; RCT, randomised control trial; RWE, real world evidence.

1. Derman BA, et al. Blood Rev. 2022;53:100913. 2. Shah JJ, et al. Clin Lymphoma Myeloma Leuk. 2017;17:575–583. 3. Richardson PG, et al. Blood Cancer J. 2018;8:109. 4. Visvanathan K, et al. J Clin Oncol. 2017;35:1845–1854. 5. Terpos E, et al. Blood Cancer J. 2021;11:40. 6. Chodankar D. Perspect Clin Res. 2021;12:171–174. 7. Blonde L, et al. Adv Ther. 2018;35:1763–1774. 8. Camm AJ and Fox KAA. Open Heart. 2018;5:e000788. 9. Roberts MH and Ferguson GT. Pharmacoecon Open. 2021;5:3–11. 10. Katkade VB, et al. J Multidiscip Health. 2018;11:295–304.

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