Table 5.

Strategic Directions for Advancing JAK Inhibitor Therapies in Inflammatory and Stress-Related Disorders: A Focus on Combination Approaches

Category	Findings/Current Applications	Future Research Directions and Considerations	References
Specificity	Isoform-specific inhibitors such as filgotinib and upadacitinib	Development of targeted cotherapies that leverage the specificity of Jakinibs alongside other agents	[274, 277, 278]
	Liposomal formulations for targeted drug delivery	Use of targeted release systems that deliver both Jakinibs and complementary agents to specific cells or tissues	[279, 280]
Therapeutic Efficacy	Efficacy in treating inflammatory conditions such as rheumatoid arthritis	Further research into the synergistic effects of Jakinibs with SSRI or benzodiazepines in stress disorders	[272, 273]
	Combination with methotrexate or monoclonal antibodies	Assessment of Jakinibs in combination with anti-inflammatory agents like corticosteroids or with neurotrophic factors like BDNF in stress disorders	[276]
	Biomarker-guided therapies in cancer	Development of precision medicine approaches that tailor combination therapies based on individual patient profiles	[281, 282]
Safety and Side Effects	Immunological concerns such as immunosuppression	Detailed pharmacokinetic studies to determine optimal dosage regimes that minimize adverse effects when using combination therapies	[283]
Regulatory Aspects	FDA-approved for specific conditions	Multiphase clinical trials to assess the safety and efficacy of combinatorial therapies with the aim of regulatory approval