What are reciprocal changes?

From the Guidelines

Reciprocal changes in the context of biosimilar-to-biosimilar switching are not directly related to ECG changes, but rather refer to the practice of switching a patient from one biosimilar to another, which may be medically prudent or necessary to address intolerance issues, improve convenience, or reduce costs. The decision to switch a patient's treatment from one biosimilar to another is emerging as a potential practical option, especially with the increasing number of affordable biosimilars entering the marketplace 1.

Key Considerations

• The lack of clinical guidelines to address the concept of cross-switching between biosimilars contributes to prescriber hesitancy 1.
• Biosimilars are considered "clinically equivalent" to the reference product, but there is no regulatory obligation to evaluate biosimilarity among themselves 1.
• Attempts to make indirect comparisons between biosimilars of the same reference product can be hampered by the heterogeneity of clinical trial designs 1.
• The ability of clinicians to infer the potential for similarity between biosimilars of a reference product and decide to switch a patient between them would likely improve if clinical trial designs were better standardized 1.

Medical and Non-Medical Switching

• Medical switching occurs when a switch is made to address tolerability issues, improve convenience, or for patient preference, and is typically initiated by a healthcare provider 1.
• Non-medical switching occurs when a clinically stable patient is switched to another therapeutic alternative for reasons such as cost mitigation or to ensure continued access to the same type of drug, and is often initiated by a third party such as a payer or hospital pharmacist 1.

Real-World Evidence and Recommendations

• Real-world evidence on biosimilar cross-switching is currently sparse, but available data suggest that cross-switching can be safe and effective in patients with inflammatory diseases 1.
• Consensus statements and current recommendations emphasize the importance of individualized decision-making and careful consideration of patient-specific factors when making decisions about biosimilar cross-switching 1.

From the Research

Reciprocal Changes in Antihypertensive Agents

• The use of antihypertensive agents, such as beta-blockers and angiotensin-converting enzyme (ACE) inhibitors, can have reciprocal changes in patients with diabetes mellitus 2.
• Beta-blockers can attenuate some components of the autonomic response to hypoglycemia, potentially increasing the risk of hypoglycemia, while ACE inhibitors may increase insulin sensitivity and predispose users to hypoglycemia 2.
• However, a study found that specific antihypertensive drug therapy had little impact on the risk of hypoglycemia in older diabetic patients 2.

Combination Therapy with Beta-Blockers and ACE Inhibitors

• The combination of beta-blockers and ACE inhibitors is of special interest due to their complementary actions on the sympathetic nervous system and renin-angiotensin-aldosterone system 3.
• This combination can provide effective blood pressure lowering and improved cardiovascular outcomes, allowing a greater proportion of patients to rapidly achieve treatment targets 3.
• A study examined the supporting evidence for beta-blockers and ACE inhibitors in various indications, including hypertension, arrhythmias, angina pectoris, and heart failure 3.

Comparative Effectiveness of Antihypertensive Agents

• A study compared the effectiveness of different antihypertensive agents, including beta-blockers, ACE inhibitors, calcium-blocking drugs, and diuretics, in lowering systolic blood pressure in elderly patients with previously untreated hypertension 4.
• The results showed that diuretics and calcium-blocking drugs were more effective in lowering systolic blood pressure, while beta-blockers were relatively ineffective and had more side effects 4.
• Another study discussed the importance of considering the relative importance of outcomes when assessing the certainty of evidence, and provided guidance on rating inconsistency, imprecision, and other domains 5.

Study Design and Evidence-Based Medicine

• The choice of study design, such as randomized controlled trials (RCTs) or observational studies, depends on the research question and the suitability of each design 6.
• RCTs are considered the best design to evaluate the intended effect of an intervention, but observational studies may be more suitable for evaluating unintended effects or when randomization is not possible 6.