## 4 Discussion
\begin{table}
\begin{tabular}{l c c c c c c} \hline \hline
**First Author, Year** & **Tial Acronym** & **Phase** & **N of Participants** & **Primary Endpoint** & **Outcome Measures (\% Responders)** & **\$ \\  & & & **Participants** & **Assessment** & **(Anifrolumab 300 mg/Placebo)** \\ \hline
**Intravenous administration** & & & & & **SRI-4** & **BICLA** & **CLASI** \\ \hline [PERSON], 2017 [17] & MUSE & IIb & 305 & 24 weeks & **34.3/17.6** & 53.5/25.7 & 63/30.8 \\ [PERSON], 2019 [2] & TULIP-1 & III & 457 & 52 weeks & **36/40** & 37/27 & 42/25 * \\ [PERSON], 2020 [1] & TULIP-2 & III & 365 & 52 weeks & 55.5/37.3 & **47.8/31.5** & 49/25 * \\ \hline
**Subcutaneous administration** & & & & & & \\ [PERSON], 2021 [21] & - & II & 36 & 12 weeks & -/- & -/- & 45/44 * \\ \hline \hline \end{tabular} \(\$\$\) Bold indicates the primary outcome measure. Outcome measures: BICLA, British Isles Lupus Assessment Group-based composite lupus assessment; CLASI, cutaneous lupus erythematosus disease area and severity index; SRI-4, systemic lupus erythematosus responder index-4. * at 12 weeks.  
\end{table} 
Table 1: Overview of clinical trials of anifrolumab in non-renal Systemic Lupus erythematosus. unlike the TULIP trials, the response rates steadily increased from 82% vs. 50% at 24 weeks to 91% vs. 44% at 52 weeks. The number of subjects was small, and this phase II trial was also not designed to assess any differences in the CLASI response. One possible explanation for the steadier increase compared to the rapid rise in response rates with the intravenous administration may be the slower absorption and biological efficacy following a subcutaneous application. Furthermore, it has been shown that IFN signaling has a central role in SLE skin pathology as the IFN signature correlates with cutaneous disease activity in SLE [24], and IFN pathways contribute to enhancing apoptosis of skin cells interfering with the protective Langerhans cell-keratinocytes axis [25]. More recently, these processes have been shown to be mediated by keratinocytes and dendritic cells in non-lesional skin lesions [26]. The available clinical trial data regarding musculoskeletal manifestations demonstrate an improvement in the phase IIb trial MUSE [17]. Of those patients with \(\geq\)8 tender and swollen joints, the percentual difference at 24 weeks of ANI responders (n = 46) was 8.9% (\(p\) = 0.351) compared to PBO (n = 37) at a dose of 300 mg. However, at 52 weeks, 48.6% (PBO) vs. 69.6% (ANI 300 mg) of patients responded (percentual difference of 21%, \(p\) = 0.038) [17]. In the TULIP-1 trial, 22/68 (32%) PBO-treated patients versus 33/70 (47%) ANI-treated patients had a \(\geq\)50% reduction in active joints at 52 weeks [2]. Lastly, in the TULIP-2 trial, 42.4% of ANI-treated patients with \(\geq\)6 swollen or tender joints had a non-statistically significant response compared to PBO (37.5%, \(p\) = 0.55) [1]. Taken together, numerically more patients with at least six swollen or tender joints treated with ANI had a 50% or greater reduction from baseline to 52 weeks in the swollen joint count (57% vs. 46%, \(p\) = 0.027), and a 50% vs. 43% reduction in the tender joint count (\(p\) = 0.095). Thus, ANI seems to lead to an improvement of joint manifestations in a relevant proportion of patients after 52 weeks.