Open questions on the management of targeted therapies for the treatment of systemic sclerosis-interstitial lung disease: results of a EUSTAR survey based on a systemic literature review

Abstract

Background: The results of randomized controlled (RCT) and retrospective studies have expanded the armamentarium of drugs for systemic sclerosis (SSc) – interstitial lung disease (ILD) treatment. The correct positioning of these drugs is not yet clarified. Objectives: Systemic literature review (SLR) on rituximab (RTX), tocilizumab (TCZ), nintedanib and abatacept (ABT) for the treatment of SSc-ILD. The results of the SLR were used to create a dedicated survey. Design: The study was performed as a systematic review. Data sources and methods: the SLR was performed using the following terms: “(systemic sclerosis OR scleroderma) AND (interstitial lung disease OR lung fibrosis OR pulmonary fibrosis) AND (rituximab OR tocilizumab OR abatacept OR nintedanib)”. The results of the SLR were integrated in a survey including 8 domains. These were sent to all EUSTAR members and to the participants of the 2020 Scleroderma World Congress. Results: 41 studies (34 on RTX, 5 on TCZ, 2 on ABT, and 1 on nintedanib) were identified. RCTs supported the use of TCZ and nintedanib, while retrospective studies supported the use of RTX for SSc-ILD. No clear data were obtained about ABT. The survey showed that RTX is the most available option (96%) whereas the most frequent reason for targeted therapy introduction is lung progression while on csDMARDs (86% RTX, 59% TCZ and 63% nintedanib). Combination therapy was the most frequently mentioned therapeutic scheme for nintedanib (75%) and RTX (63%). Physicians’ perception of safety was similar for all drugs, while drug efficacy was the same for RTX and nintedanib, followed by TCZ (4.8 ± 2). The most frequently raised concerns pertained to efficacy, safety and combination regimens. Conclusion: Our SLR supports the use of RTX, TCZ and nintedanib for SSc-ILD patients and underlines the need for more data about upfront combination versus monotherapy. It also highlighted the need to identify predictors supporting drug choice according to both pulmonary and extra-pulmonary manifestations.

Real-life efficacy and safety of nintedanib in systemic sclerosis-interstitial lung disease: data from an Italian multicentre study

“…In fact, a recent EUSTAR survey showed how the majority of physicians (88%) expert in treating patients with SSc-ILD consider that NTD should be combined with other immunosuppressive treatments instead of using it as monotherapy. 16 Moreover, it should also be noticed that besides the efficacy in preserving lung function, our study showed that the progressive phenotype (defined according to OMERACT definitions) observed in 60% of our patients could be effectively counteracted in the majority of patients with NTD therapy. This result is particularly important as patients with progressive ILD phenotype, being a significant percentage of the whole population with SSc, 5 are the most difficult to treat.…”

“…The combination of NTD with other immunosuppressive drugs is not a novelty. In fact, a recent EUSTAR survey showed how the majority of physicians (88%) expert in treating patients with SSc-ILD consider that NTD should be combined with other immunosuppressive treatments instead of using it as monotherapy 16. Moreover, it should also be noticed that besides the efficacy in preserving lung function, our study showed that the progressive phenotype (defined according to OMERACT definitions) observed in 60% of our patients could be effectively counteracted in the majority of patients with NTD therapy.…”

Interstitial Lung Disease

“…However, several major knowledge gaps have been identified. 68 In our opinion, future research should focus on the practical use of the available drugs to answer specific unmet needs in the therapeutic approach. This would allow us to move beyond expert opinions and compensate for the lack of real evidence on different points with specific strategies, including initiation, combination, and continuation of treatment and monitoring (Box 1).…”

Anti-U11/U12 Antibodies as a Rare but Important Biomarker in Patients with Systemic Sclerosis: A Narrative Review

“…anti-U11/U12 antibodies are more prevalent in CTP negative patients [ 39 ]. However, this is not only limited to nintedanib, but applies to other novel and alternative treatment approaches in SSc-ILD, including agents with strong-supporting evidence, such as tocilizumab and rituximab [ 55 , 56 ], or others with biological or promising compoundssuch as abatacept, lenabasum, romilkimab, belimumab, bermekimab, brodalumab, tofacitinib, or even rituximab [reviewed in [ 1 , 57 ]].…”