What are the newest immune modulators?

From the Guidelines

The newest immunomodulators for the treatment of multiple myeloma include bispecific antibodies such as teclistamab, elranatamab, and talquetamab, which have shown promising results in clinical trials 1. These medications work by targeting specific immune pathways, including BCMA, to modulate the immune response and reduce the risk of infections. The use of these bispecific antibodies has been associated with an increased risk of infections, including pneumocystis jirovecii pneumonia, cytomegalovirus reactivation, and hepatitis B virus reactivation 1. However, the benefits of these medications in terms of reducing morbidity and mortality in patients with multiple myeloma outweigh the risks, and they are considered a valuable treatment option for patients who are refractory to other treatments 1. In addition to bispecific antibodies, other immunomodulators such as JAK inhibitors, including baricitinib, have shown promise in reducing mortality in patients with COVID-19, and may also be considered for use in patients with multiple myeloma 1. The dosing and administration of these medications vary, and treatment is typically ongoing for chronic inflammatory or autoimmune conditions. Key points to consider when using these medications include:

• Monitoring for infections and adjusting prophylaxis and treatment as needed
• Managing cytokine release syndrome and other adverse events
• Considering the use of JAK inhibitors, such as baricitinib, in patients with COVID-19
• Weighing the benefits and risks of bispecific antibodies in patients with multiple myeloma.

From the FDA Drug Label

Siponimod is an S1P receptor modulator. Siponimod binds with high affinity to S1P receptors 1 and 5. The newest immi modulator mentioned in the provided drug labels is Siponimod, which is an S1P receptor modulator. It works by binding to S1P receptors 1 and 5, reducing the number of lymphocytes in peripheral blood. 2

From the Research

Newest Immune Modulators

• The newest immune modulators include tofacitinib, baricitinib, upadacitinib, filgotinib, and peficitinib, which are Janus kinase (JAK) inhibitors used to treat rheumatoid arthritis (RA) 3, 4, 5, 6, 7.
• These JAK inhibitors have been shown to be effective in improving RA control, with varying efficacy and safety profiles 3, 4, 5, 6, 7.
• Upadacitinib and filgotinib have been found to be equivalent therapeutic alternatives, while baricitinib and upadacitinib are also equivalent due to a lack of clear differences and showing superiority over placebo 5.
• Peficitinib has been shown to have a high ACR20 response rate, with peficitinib 150 mg monotherapy having the highest probability of being the best treatment for achieving the ACR20 response rate 7.

Efficacy and Safety

• The efficacy of these JAK inhibitors has been evaluated in several studies, with results showing that they are more effective than placebo in achieving ACR20, ACR50, and ACR70 responses, as well as improving DAS28-CRP scores 3, 4, 5, 6, 7.
• The safety profiles of these JAK inhibitors have also been evaluated, with results showing that they have similar safety profiles, with no significant differences in serious adverse events, except for tofacitinib 5 mg 7.
• However, it is still necessary to select the appropriate therapeutic regimen based on the actual clinical situation, and to monitor the occurrence of adverse events in high-risk RA patients with medication 6.

Comparison of JAK Inhibitors

• A network meta-analysis study compared the efficacy of five approved JAK inhibitors, including tofacitinib, baricitinib, upadacitinib, filgotinib, and peficitinib, as monotherapy and combination therapy in patients with moderate-to-severe active RA 6.
• The results showed that all JAK inhibitors performed better than placebo, with upadacitinib 30 mg, upadacitinib 15 mg, upadacitinib 15 mg + csDMARD, and baricitinib 4 mg + csDMARD being recommended treatment options with relatively good efficacy and safety 6.