APLs are a major determinant of the increased cardiovascular risk in patients with SLE. They adversely affect clinical manifestations, damage accrual and prognosis. Apart from the antibodies included in the 2006 revised classification criteria for APS, other non-classical aPLs might help in identifying SLE patients at increased risk of thrombotic events. The best studied are IgA anti-β2-glycoprotein I, anti-domain I β2-glycoprotein I and aPS-PT. Major organ involvement includes kidney and neuropsychiatric systems. aPL/APS severely impacts pregnancy outcomes. Due to increased thrombotic risk, these patients require aggressive cardiovascular risk factor control. Primary prophylaxis is based on low-dose aspirin in high-risk patients. Warfarin is the gold-standard drug for secondary prophylaxis.

For many years, the failure of randomized controlled trials (RCTs) has prevented patients with systemic lupus erythematosus (SLE) from benefiting from biological drugs that have proved to be effective in other rheumatological diseases. Only two biologics are approved for SLE, however they can only be administered to a restricted proportion of patients. Recently, several phase II RCTs have evaluated the efficacy and safety of new biologics in extra-renal SLE and lupus nephritis. Six drug trials have reported encouraging results, with an improvement in multiple clinical and serological outcome measures. The possibility of combining B-cell depletion and anti-BLyS treatment has also been successfully explored.

Lupus nephritis (LN) is a frequent and serious complication of systemic lupus erythematosus (SLE), impairing patients’ quality of life and significantly increasing mortality. Despite optimizing the use of conventional immunosuppressants and other biological drugs, its management remains unsatisfactory. This is mainly due to the heterogeneity of SLE, but also to insufficiently effective treatment regimens and clinical trial limitations (strict criteria, low number of patients included, and side effects). Most clinical trials of new biological therapies have failed to meet their primary endpoints in both general SLE and LN, with only two biological drugs (belimumab and anifrolumab) being approved by the Food and Drug Administration (FDA) for the treatment of SLE. Recently, several Phase II randomized controlled trials have evaluated the efficacy and safety of new biologics in LN, and some of them have demonstrated an improvement in clinical and laboratory measures. Multi-target therapies are also being successfully developed and encourage a belief that there will be an improvement in LN outcomes.

The aims of this systematic literature review (SLR) were to identify the effects of approved biological and targeted synthetic disease modifying antirheumatic drugs (b/tsDMARDs) on synovial membrane of psoriatic arthritis (PsA) patients, and to determine the existence of histological/molecular biomarkers of response to therapy. A search was conducted on MEDLINE, Embase, Scopus, and Cochrane Library (PROSPERO:CRD42022304986) to retrieve data on longitudinal change of biomarkers in paired synovial biopsies and in vitro studies. A meta-analysis was conducted by adopting the standardized mean difference (SMD) as a measure of the effect. Twenty-two studies were included (19 longitudinal, 3 in vitro). In longitudinal studies, TNF inhibitors were the most used drugs, while, for in vitro studies, JAK inhibitors or adalimumab/secukinumab were assessed. The main technique used was immunohistochemistry (longitudinal studies). The meta-analysis showed a significant reduction in both CD3+ lymphocytes (SMD −0.85 [95% CI −1.23; −0.47]) and CD68+ macrophages (sublining, sl) (SMD −0.74 [−1.16; −0.32]) in synovial biopsies from patients treated for 4–12 weeks with bDMARDs. Reduction in CD3+ mostly correlated with clinical response. Despite heterogeneity among the biomarkers evaluated, the reduction in CD3+/CD68+sl cells during the first 3 months of treatment with TNF inhibitors represents the most consistent variation reported in the literature.

Objective. Interstitial lung disease (ILD) is rare, but it is one of the most frequent extra-articular manifestations and a relevant cause of morbidity and mortality in rheumatoid arthritis (RA). Over the past few years, Janus kinase inhibitors (JAKis) have been reported to have promising efficacy in the treatment of active RA, but recent concerns have been raised about their safety profile, namely, malignancy and cardiovascular disease, limiting their use to certain patient categories. Methods. The objective of this narrative review is to summarize the current evidence of the efficacy and safety of JAKis in RA-ILD management, investigating a possible emerging role for this drug class in such a subset of patients. Results. Current studies focusing on JAKis in RA-ILD are scarce, but they globally report an overall stabilization of respiratory symptoms, functional data, and radiographic extension of ILD. In some cohorts, JAKis determined even an encouraging improvement in lung disease, and few reports presented good tolerability of JAKis in combination with antifibrotics. Concerning the safety profile, no significant increased risk of pulmonary infection has been reported. Conclusions. Thus far, evidence regarding the role of JAKis in the treatment of RA-ILD remains relatively limited, and additional prospective studies are needed to better understand the place of JAKis, if any, in preventing/stabilizing ILD in RA patients.