*3.2. Evaluation of Sublingual Immunotherapy Efficacy*

Of the 98 total patients, 66 (67.34%) patients underwent SLIT for a single allergen and 32 (32.65%) underwent SLIT for two allergens (Table 3). Each patient received the maximum tolerated dose, per the manufacturers' recommendations. SLIT was well tolerated, and no discontinuation due to severe adverse drug effects was registered.

Patients experienced a significant improvement in symptoms at T12 (mean MSS-12 = 31.11 ± 16.88) and T24 (mean MSS-24 = 27.07 ± 15.01) compared to T0 (mean MSS-0 = 80.97 ± 8.24). Indeed, ANOVA conducted on MSS revealed a significant difference between MSS-0 and MSS-12 (*p* < 0.001) and MSS-0 and MSS-24 (*p* < 0.001) (Figure 1A). Although an additional symptom improvement was recorded at T24, no significant difference was observable between MSS-12 and MSS-24 (*p* = 0.07). Accordingly, after 12 or 24 months of SLIT, the clinical improvement assessed by ΔMSS-12(%) and ΔMSS-24(%) was 61.35% and 67.71%, respectively.

To evaluate whether the number of allergens administered may affect SLIT efficacy, we compared patients undergoing single-allergen SLIT (Mono SLIT) with patients undergoing two-allergen SLIT (MIX-SLIT). Both patient groups showed a significant improvement of symptoms at T12 (Mono SLIT-MSS-12 = 29.68 ± 17.59; MIX-SLIT-MSS-12 = 34.06 ± 15.15) and T24 (Mono SLIT-MSS-24 = 26.00 ± 14.91; MIX-SLIT-MSS-24 = 29.28 ± 12.05) as compared to T0 (Mono SLIT-MSS-0 = 81.55 ± 7.75; MIX-SLIT-MSS-0 = 79.75 ± 9.18) (Figure 1B). In addition, no significant difference was found when ANOVA was conducted by comparing ΔMSS-12(%) and ΔMSS-24(%) in patients treated with a single-allergen SLIT and patients treated with a two-allergen SLIT (*p* = 0.11 and *p* = 0.07, respectively). These results indicate that the efficacy is comparable when one or two allergens are used for SLIT.

Next, we compared SLIT efficacy between patients with only rhinitis and rhinitis associated with asthma. Figure 1C illustrates that both patient groups showed a significant improvement in symptoms at T12 (rhinitis-MSS-12 = 25.90 ± 13.95; rhinitis+asthma-MSS-12 = 36.33 ± 18.05) and T24 (rhinitis-MSS-24 = 22.61 ± 11.71; rhinitis+asthma-MSS-24 = 31.53 ± 14.90) as compared to T0 (rhinitis-MSS-0 = 78.33 ± 8.55; rhinitis+asthma-MSS-0 = 83.60 ± 7.07). When ANOVA was conducted on ΔMSS, values revealed that ΔMSS-12(%) and ΔMSS-24(%) were significantly higher in patients with only rhinitis compared to patients with rhinitis and concomitant asthma (*p* < 0.05) (Figure 1C). These results indicate that SLIT was effective in both patients with allergic rhinitis and concomitant asthma. However, they also suggest that patients affected only by rhinitis can experience a better response to SLIT compared to patients with associated asthma.

**Figure 1.** Sublingual immunotherapy (SLIT) efficacy assessment in the whole cohort (**A**), in patients treated with single-allergen (Mono SLIT) and two-allergen SLIT (MIX-SLIT) (**B**), and with allergic rhinitis and concomitant asthma (**C**). MSS-0: mean symptom score at T0; MSS-12: mean symptom score at T12; MSS-24: mean symptom score at T24; ΔMSS-12 (%): percentage difference between the MSS-0 and MSS-12; ΔMSS-24 (%): percentage difference between MSS-0 and MSS-24; ns: not significant; \*,\*\*: *p* < 0.001; §: *p* < 0.05.
