84.6%) . Etanercept Etanercept was not reported to interfere with the humoral response to pneumococcal polysaccharide antigen challenge. vaccination. In contrast, treatment with biological agents is not associated with lower antibody response and can thus be continued safely. = 38) or nonpegylated interferon for at least 3 months (= 33), assessing humoral response to tetanus-diphtheria, meningococcus C, and pneumococcal vaccination. Tetanus-diphtheria toxoid (recall antigen), conjugated meningococcal C polysaccharide (neoantigen), and pneumococcal vaccine mounted a comparable immune response (response was defined as a 2-fold increase from pre- to postvaccination titer) between the two treatment groups . A positive immune response, defined as a 4-fold increase in antibody titer to the three vaccines, was achieved in both treatment groups, though no unfavorable control represented by healthy or untreated subjects was included . 4.1.3. Methotrexate A consistent body of evidence showed lower response to vaccination during methotrexate therapy. The unfavorable impact of methotrexate on humoral response was detected when used β-cyano-L-Alanine both in monotherapy and in combination with biologic agents. Reduced antibody titers were observed after exposure to numerous nonlive vaccines, including seasonal influenza computer virus and pneumococcus [19,20,21,22,23,24,25,26]. Studies on rheumatoid arthritis patients demonstrated a significant and substantial enhancement of the postvaccination humoral response to trivalent seasonal influenza vaccine if methotrexate was discontinued for 2C4 weeks [27,28]. Nevertheless, because a 4-week discontinuation was associated with an increased risk of disease worsening, a shorter period of discontinuation (2 weeks) improved the immunogenicity of seasonal influenza vaccination minimizing the risk of disease flaring [27,28]. 4.2. Novel Synthetic Medications Apremilast No information about the impact of apremilast therapy on humoral response induced by nonlive vaccines is currently available. 4.3. Biologic Brokers There is consensus among experts, and national and international guidelines in avoiding vaccination with attenuated live vaccines during therapy with biologic brokers, independently from their target and mechanism of action. Contrarily, nonlive vaccines can be administered in patients undergoing therapy with biologics as their selective immune-modulation does not impact vaccine-induced antibody β-cyano-L-Alanine production (Table 2). Table 2 Details about biologics and vaccination. < 0.0001), concomitant disease-modifying antirheumatic drugs (DMARDs) use (< 0.044), and protective antibody titers at baseline (< 0.0001) significantly reduced the response rate to pneumococcal vaccine in the adalimumab group compared to the placebo group . The number of patients achieving a 2-fold increase in 3 of the 5 pneumococcal titers was lower in patients treated with adalimumab and methotrexate (10/55, (18.2%)) compared to patients receiving placebo and methotrexate (17/59, (28.8%)) or adalimumab alone (27/44, (61.4%)). Similarly, a lower quantity of patients achieved the same response if treated with adalimumab and other DMARDs (hydroxychloroquine and/or leflunomide) compared to patients receiving placebo and other DMARDs (2/17, (11.8%) vs. 11/32, (34.4%)) or adalimumab alone (35/82, (42.7%)). Percentages of patients achieving protective antipneuomococcal antibody titers were comparable in both treatment groups (adalimumab: 85.9%, placebo: 81.7%), while protective anti-influenza antibody titers were detected in 94.5% and 98% of patients treated with placebo and adalimumab, respectively . Considering high anti-influenza antibody titers (4-fold increase), a smaller, although not statistically significant percentage of patients receiving adalimumab achieved this vaccine response compared to placebo (51.5% vs. 63.3%), likely due to the presence of pre-existing protective anti-influenza antibodies . There was contrasting data around the response Tal1 rate to influenza vaccination obtained with concomitant use of methotrexate: a reduced response was observed, but neither β-cyano-L-Alanine methotrexate nor other DMARDs significantly lowered humoral response in adalimumab-treated patients compared.