Beyond Monotherapy: Exploring the Efficacy and Safety of Dual Biologic Strategies in Rheumatic Diseases

Although numerous biologic and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) are available, substantial number of rheumatic patients fail to achieve therapeutic goals with sequential monotherapy. Dual biologic therapy (DBT) may overcome treatment resistance by concomitantly inhibiting multiple inflammatory pathways. In rheumatoid arthritis, DBT shows moderate efficacy improvements but consistently higher serious infection rates compared to monotherapy, particularly with rituximab and JAK inhibitor combination-based regimens. In psoriatic arthritis, studies demonstrate possible benefits especially with combinations targeting alternate pathways, eg, apremilast with biologics or IL-17/IL-23 inhibitors with TNF blockers, though safety concerns exist. The multi-domain nature of PsA makes DBT particularly attractive in achieving global disease control. In axSpA, evidence of efficacy is also limited but encouraging in treatment-refractory disease. However, major research gaps persist. Data remain limited and largely heterogeneous, with limited disease-specific studies and a paucity of randomized controlled trials (RCTs). Most available reports derive from small case series or single-center experiences, limiting the generalizability of findings. Geographic variation further complicates interpretation, as infection risk, treatment accessibility, and pharmacovigilance capacity differ markedly between developed and resource-limited regions. Therefore, this narrative review aims to summarize current evidence while emphasizing the unmet clinical and research needs surrounding DBT, highlighting the necessity for systematic reviews, large-scale registries, and context-specific studies to inform safe and equitable clinical application worldwide. While DBT may be beneficial in carefully selected patients with treatment-refractory disease, current evidence does not consistently demonstrate increased efficacy. Thus, DBT should be reserved for refractory cases where benefits outweigh risks.