Objectives While glucocorticoids have been considered the standard of care for IgG4-related disease (IgG4-RD), rituximab is increasingly used off-label. We aimed to evaluate the glucocorticoid-sparing ability of rituximab using real-world data. Methods This was an observational multicenter study including adult IgG4-RD patients from three European referral centers treated with glucocorticoids or rituximab (± glucocorticoids). The primary endpoint was no glucocorticoid use at 6 months. Secondary endpoints included treatment response (≥ 2-point decline in responder index (RI)), remission (RI = 0) and flare. Key safety measures included infections requiring hospitalization, and death. We applied logistic regression adjusted for potential confounders. Findings We included 167 patients, 115 (68.9 %) in the rituximab and 52 (31.1 %) in the glucocorticoid group. At baseline, the rituximab group was younger, had longer disease duration, more often relapsing disease and higher RI score than the glucocorticoid group. Despite these indicators of more severe disease, a higher proportion of patients in the rituximab group were free from glucocorticoids by 6 months (OR 3.62, 95 % CI 1.06-12.43, p = 0.040). The median cumulative prednisolone dose at 12 months was 1640.0 mg (IQR 150.0-2578.8) for the rituximab group, and 2950.0 mg (IQR 2302.0-4120.0) for the glucocorticoid group (p < 0.001). The secondary endpoints were similar between groups. Interpretation While the rituximab-treated patients in this study had more severe IgG4-RD than the glucocorticoid-treated comparators, treatment with rituximab was associated with similar effectiveness endpoints, while significantly reducing glucocorticoid use.

BACKGROUND Cryoglobulinemia is a rare disease with a prevalence of <5 cases per 10 000. In many cases there is significant diagnostic delay, leading to years of morbidity. There are no randomized trials on non-infectious type II cryoglobulinemia, and choice of therapy is based on clinical expertise and observational data. Therapy based on the monoclonal anti-CD20 antibody rituximab in combination with glucocorticosteroids is the preferred choice in many centers. This strategy induces clinical remission in two-thirds of patients. However, one-third of the initially-responding patients experience relapse within the first year. As such, many patients will not achieve sustained remission. CASE REPORT We describe the clinical course of 2 patients with non-infectious type II cryoglobulinemia. They were initially treated according to standard clinical practice, without lasting symptom relief. A novel treatment strategy was attempted, targeting the underlying B-cell clone responsible for the production of disease-inducing monoclonal immunoglobulins. These protocols, initially developed for treatment of chronic cold agglutinin disease, contain rituximab in combination with fludarabine or bendamustine. Sustained clinical, immunological, and hematological remissions were achieved in both patients, and the treatment was well tolerated with no need for hospitalization or other supportive measures. CONCLUSIONS Treating patients with type II cryoglobulinemia using chemo-immune therapy in the same regimens as used in cold agglutinin disease could be considered as a therapeutic option. Based on our observations in the 2 patients described in this case series, this approach seems feasible and well tolerated. Deep sustained remissions may be possible.

Background Interstitial lung disease in Sjögren disease (SjD-ILD) is a clinically relevant and potentially progressive complication, yet treatment remains empirical and poorly supported by evidence. Methods This multicentre observational study across three European expert centres (Oslo, Zurich, and Vienna) included patients with SjD-ILD who were diagnosed between 1997 and 2025, fulfilled the 2016 ACR/EULAR SjD criteria and had ILD confirmed by high-resolution computed tomography (HRCT). Treatment patterns and pulmonary function were analysed across four predefined calendar periods (≤2006, 2007-2011, 2012-2016, ≥2017). Outcomes included therapeutic patterns, factors associated with treatment, longitudinal changes in pulmonary function and mortality. ILD progression and improvement were defined as absolute forced vital capacity (FVC) change (≥5% or ≥10%) over 12 ± 3 and 24 ± 3 months, and by 5-year all-cause mortality. Comparisons across periods used trend tests, and logistic regression was applied to identify factors associated with treatment. We involved people with lived experience in the study design and implementation. Results Among 191 patients with SjD-ILD (mean age 59.9 ± 13.6 years, 81% females), 122 (63.9%) ever received immunosuppressive therapy, increasing from 52.4% before 2006 to 71.3% after 2017 (p = 0.03). Glucocorticoids were used in 81 patients (42.4%), rituximab in 48 (25.1%), azathioprine in 33 (17.3%), and mycophenolate-mofetil in 32 (16.8%). Patients with higher dyspnoea severity (OR 3.34, 95% CI 1.43-7.80) and FVC<70% predicted (OR 3.48, 95% CI 1.54-7.90) were more likely to be treated. Lymphocytic interstitial pneumonia was treated less frequently than non-specific interstitial pneumonia (OR 0.40, 95% CI 0.18-0.90). Over time, ILD progression remained largely unchanged, while ILD improvement (≥5% FVC increase) increased from 2.9% to 11.9% (p = 0.03). Over a mean follow-up of five years, 9 patients (4.8%) died, with no significant changes in mortality rates over time. Conclusion Management of SjD-ILD has evolved towards broader and more consistent use of immunosuppressive therapy. However, a substantial proportion of patients remained untreated, and treatment was more frequently initiated in patients with greater symptom burden and impaired lung function, which emphasises the need for earlier and evidence-based intervention strategies.

Background While the presence of distinct imaging abnormalities by high-resolution CT (HRCT) defines interstitial lung disease (ILD), there is a relative lack of validated methods to quantify these abnormalities in clinical practice, limiting ILD severity and progression assessments. We aimed to validate a semi-quantitative method for lung fibrosis assessment in patients with systemic sclerosis associated ILD (SSc-ILD) by standard and low-dose HRCT, considering lung structure and function as integral components of ILD evaluation.Methods SSc patients from Oslo and Zurich with HRCT images, pulmonary function tests, including forced vital capacity (FVC), diffusing capacity for carbon monoxide (DLCO) and the 6-minute walk test with oxygen (O2) desaturation were enrolled. We validated the semi-quantitative fibrosis extent method by HRCT using criteria for content and construct validity, discrimination, sensitivity to change and feasibility, as well as inter- and intra-rater variability.Results 65 SSc patients from Zurich and 90 from Oslo were included. Significant correlations were observed between the extent of fibrosis on HRCT and FVC (r=−0.517, p<0.001), DLCO (r=−0.400, p<0.001) and O2 desaturation (r=−0.500, p<0.001), indicating content, construct and criterion validity. Discrimination and sensitivity to change assessments showed moderate correlation with DLCO (r=−0.377, p=0.003) but not with FVC or O2 desaturation. Inter- and intra-rater variability demonstrated excellent reliability (κ=0.891 and κ=0.996, respectively), with HRCT quantification averaging 9–15 min, indicating high feasibility.Conclusion This study confirms that semi-quantitative fibrosis assessment of HRCT for SSc-ILD meets most validation criteria, supporting its use in clinical practice and showing additive value of structural to functional ILD assessment.

OBJECTIVE:Assess relative effectiveness and safety of rituximab (RTX) across the four phenotypes of IgG4-related disease (IgG4-RD). METHODS:We included phenotypically defined adult IgG4-RD patients treated with RTX +/- glucocorticoids (GC) who had evaluable data at 6 months on the composite primary outcome, which included: (i) treatment response (>= 2-point decline in responder index (RI)); (ii) absence of flare; and (iii) GC dose <= 7.5 mg prednisolone. Additional assessments at 6 and 12 months included remission (RI = 0 and prednisolone <= 7.5 mg), rate of infections and infusion reactions. Descriptive statistics and logistic regression were applied. RESULTS:We included 115 patients (74.8 % male, 86.1 % Caucasian) of whom 33 (28.7 %) had pancreato-hepato-biliary disease, 22 (19.1 %) retroperitoneal and aortic disease, 19 (16.5 %) head and neck-limited disease and 41 (35.7 %) Mikulicz' and systemic disease. The primary outcome was met by 80 patients (69.9 %) with no significant difference across phenotypes. Remission rate at 6 months was lower in retroperitoneal and aortic disease (4.5 %) than in the other phenotypes (18.2-36.6 %, p = 0.025) while the head and neck-limited phenotype had higher flare rate at 12 months than the others (38.9 % vs. 4.8-25.0 %, p = 0.005). In multivariable models, higher baseline RI and lower serum IgG4 associated with the primary outcome (p < 0.05). CONCLUSIONS:In this multi-center study, effectiveness of RTX did not differ across phenotypes. Our data do, however, indicate post-RTX differences in remission rates and flare risk across the phenotypes, with potential implications for surveillance and maintenance therapy.

BACKGROUND:In patients with systemic sclerosis, it is common practice to treat interstitial lung disease (ILD) in patients in whom progression has already occurred. We sought to clarify whether observed progression of systemic sclerosis-associated ILD confers risk for subsequent progression. METHODS:In this multicentre observational cohort study, based on an analysis of prospectively collected data, we included patients with systemic sclerosis-associated ILD aged 18 years or older at diagnosis, who fulfilled the 2013 American College of Rheumatology-European Association of Alliances in Rheumatology systemic sclerosis classification criteria. The main cohort (diagnosed between January 2001 and December 2019) was consecutively followed up annually over 4 years at the Department of Rheumatology at the Oslo University Hospital, Norway, and the Department of Rheumatology at the University Hospital Zurich, Switzerland. We applied four definitions of ILD progression: the primary definition was forced vital capacity (FVC) decline of 5% or more, and secondary definitions included FVC decline of 10% or more, progressive pulmonary fibrosis (PPF), and progressive fibrosing ILD (PF-ILD). We applied these definitions at each annual visit after the first (visit 1). We validated our findings in an enriched cohort that included patients from the main cohort with systemic sclerosis-associated ILD and short disease duration of less than 3 years along with patients diagnosed between January 2003 and September 2019 from the Division of Rheumatology, University of Michigan, Ann Arbor, MI, USA. Multivariable logistic regression analyses were applied to predict ILD progression and its effect on mortality. There was no involvement of people with lived experience in this study. FINDINGS:Of 231 patients with systemic sclerosis-associated ILD from the main cohort (mean age 48·0 years [SD 14·6], 176 [76%] female and 55 [24%] male), 71 (31%) had ILD progression as defined by an FVC decline of 5% or more between visit 1 and visit 2, 38 (16%) as defined by an FVC decline of 10% or more, 39 (17%) as defined by PPF, and 89 (39%) defined by PF-ILD. In multivariable logistic regression analyses, adjusted for risk factors for progressive systemic sclerosis-associated ILD and immunosuppressive treatment, we found that ILD progression, defined by FVC decline of 5% or more, from visit 1 to visit 2 reduced the risk for further progression from visit 2 to visit 3 (odds ratio [OR] 0·28 [95% CI 0·12-0·63]; p=0·002) and that there was no risk for subsequent progression using the other definitions (FVC decline of ≥10%: 0·57 [0·16-1·99; p=0·38]; PPF: 0·93 [0·39-2·22; p=0·88]; and PF-ILD: 0·69 [0·35-1·36]; p=0·28]). Using the primary definition of progression, we found the same results in the enriched systemic sclerosis-associated ILD cohort, wherein 41 (34%) of 121 patients had progression defined by an FVC decline of 5% or more (OR 0·22 [95% CI 0·06-0·87]; p=0·031). FVC decline of 5% or more was significantly associated with mortality (hazard ratio 1·66 [95% CI 1·05-2·62]; p=0·030) adjusted for other risk factors. INTERPRETATION:Systemic sclerosis-associated ILD progression does not predict further ILD progression at the next annual follow-up visit, even in an enriched population, but progression was associated with mortality. These results have implications for clinical practice because they support a paradigm shift in treatment strategy, advocating for initiating therapy in patients at risk of progression. Further research is needed to confirm these findings. FUNDING:None. TRANSLATIONS:For the German and Norwegian translations of the abstract see Supplementary Materials section.

Objectives The 2022 European Society of Cardiology and European Respiratory Society (ESC/ERS) guidelines for pulmonary arterial hypertension (PAH) recommend risk stratification to optimize management. However, the performance of generic PAH risk stratification tools in patients with SSc-associated PAH remains unclear. Our objective was to identify the most accurate approach for risk stratification at SSc-PAH diagnosis.Methods In this multicentre, international cohort study from the European Scleroderma Trials and Research (EUSTAR) group database, we screened 11 risk stratification tools upon SSc-PAH diagnosis. We compared the performance of the three top-ranked tools to predict mortality with the ESC/ERS three-strata model, the currently recommended tool for baseline risk assessment. We also assessed the impact of incorporating SSc-specific characteristics into the tools. Kaplan-Meier analyses and Cox regression with area under the ROC curve (AUC) were conducted.Results The ESC/ERS three-strata model had a lower ability to predict mortality than the ESC/ERS four-strata model, 'SPAHR updated' and 'REVEAL Lite 2'. The ESC/ERS four-strata model divided 'intermediate-risk' patients into two groups with significantly different long-term survival rates and is the easiest applicable tool. Incorporating SSc-specific characteristics did not significantly improve the predictive ability of any model, but a low diffusing capacity of the lung for carbon monoxide (DLCO) was an independent predictor of mortality.Conclusion Considering its ability to predict mortality, risk segregation capabilities and clinical applicability, this study provides a rationale for using the simplified ESC/ERS four-strata model at SSc-PAH diagnosis as an alternative to the comprehensive ESC/ERS three-strata model. We propose considering DLCO as an individual prognostic marker in SSc-PAH.

Background: Systemic sclerosis (SSc) is a chronic multi-system autoimmune disease associated with disability and reduced quality of life. SSc specific patient reported outcome measures (PROMs) are in use for this disease-group to understand the complexity and impact of the disease on the patients' health status better. Other PROMs are generic, as the EuroQol Five-Dimensional descriptive system (EQ-5D), used to evaluate quality of life, and frequently included as secondary endpoints in randomized trials. Objectives: To describe health status in a Norwegian SSc cohort compared with population norms and to assess change over time measured with EQ-5D questionnaire. Methods: The EQ-5D-5L was included as secondary endpoint in the Norwegian 20 week randomized ReSScue trial. The first part of this PROM consists of five dimensions (mobility, self-care, usual activities pain/discomfort and anxiety/depression) with five answers (1=no problems, 2=moderate problems, 3=severe problems, 4=extreme problems, 5=unable to do). The EQ-5D-5L index was calculated by crosswalk index values using the United Kingdom (UK) Dolan value set in absence of a scoring algorithm for Norway. The index value reflects how good or bad the health state is according to the preferences of the general population of a country/region. Results vary from -0.59 (health worse than dead) and 1 (perfect health). The second part of the questionnaire consists of a single visual analogue scale (VAS) through which patients are asked to rate their health of the day from 0-100 were 0 means the worst health Patients age- and sex matched normative data were obtained from the first Norwegian population norms for the EQ-5D-5L consisted of 12790 randomly selected Norwegian citizens (1713 woman) who were aged 18 years and older [1]. Standardized response mean (SRM) was computed and interpreted according to Cohen`s effect size index, in which 0.2 = small difference, 0.5 = moderate difference, and 0.8 = more as a large difference. Results: The study cohort included 67 SSc patients, with mean age 61 years and mean disease duration of 10 years (Table 1). In the EQ-5D dimensions, proportion of patients reporting problems compared to population norms was 96.9 % vs 69 % (p<0.001) for pain and 53.8% vs 29 % (p=0.003) for activity (Figure 1A). The changes from baseline to week 12 and 20 in patients reporting problems are shown in Figure 1B. The mean (SD) difference between patients and the Norwegian norms in the EQ-5D index score was small -0.033 (-0,16), p=0.147). The EQ5D VAS assessing "your own health today" was at baseline 61.7 (18) showing a mean difference (SD) of -16.7(19), (p<0.001) compared to the Norwegian norms. Overall the repeated measures analyses adjusted for age and gender showed no change over time for the EQ5D-index (SRM 0.02 (95% CI -0.4-0.4; p=0.105) or for the EQ-5D VAS (SRM -0.01 (95% CI -0.2-0.2; p=0.958. Conclusion: Compared to the population norms the EQ-5D dimensions pain, activity and anxiety as well as the EQ-5D VAS were significantly impaired in SSc patients. Nor the EQ-5D index score or the EQ-5D VAS showed sensitivity to change. REFERENCES: [1] Garratt AM et.al. Norwegian population norms for the EQ-5d-5L; results from a general population survey. Acknowledgements: NIL. Disclosure of Interests: Torhild Garen: None declared, Cristina Nita: None declared, Håvard Fretheim: None declared, Imon Barua: None declared, Maylen N Carstens: None declared, Henriette Didriksen: None declared, Vikas K. Sarna: None declared, Øyvind Midtvedt: None declared, Øyvind Molberg: None declared, Anna-Maria Hoffmann-Vold Boehringer Ingelheim, Boehringer Ingelheim, Janssen, Medscape, Merck Sharp & Dohme, Novartis and Roche, ARXX, BMS, Boehringer Ingelheim, Genentech, Janssen, Medscape, Merck Sharp & Dohme and Roche, Boehringer Ingelheim, Janssen.

Background: Patients with systemic sclerosis (SSc) report loss of bowel control as one of the most distressing gastrointestinal (GI) manifestations of their disease. Nevertheless, despite the pivotal aspect of fecal incontinence (FI) care, our understanding of its prevalence and true impact on SSc patients remains elusive. Objectives: The study had three aims; (i) assess prevalence and burden of FI symptoms by two different patient-reported outcome measures, (ii) identify potential associations between FI symptoms and baseline SSc characteristics, and (iii) determine predictive factors for worsening of FI-related quality of life over time in SSc patients with lower GI disease. Methods: In the 20-week multicenter randomized clinical trial (ReSScue) [1] FI symptoms were assessed in 67 SSc patients with moderate to severe lower GI symptoms at baseline, 12 and 20 weeks using the Fecal Incontinence Quality of Life (FIQL) scale and University of California Los Angeles Scleroderma Clinical Trial Consortium GIT 2.0 (UCLA GIT) scale. Patients reporting presence of FI symptoms at all three timepoints were defined as having "severe FI". Using multivariable logistic regressions, we assessed associations between baseline FI and frequency of FI with patient characteristics. Next, we assessed associations between FI, by UCLA GIT fecal soilage score and FIQL subscales, as well as ScleroID, HAQ-DI, EuroEQ-5D, patient and physician global assessment and VAS fatigue scale, using Pearson's correlation analysis. Linear mixed-effect models were applied to unveil predictors of FIQL score behavior over time. Results: In the entire cohort, 72% (48/67) reported FI on the FIQL scale, in contrast to 33% (22/67) using the UCLA GIT. Altogether, 14 SSc patients met the definition of "severe" FI. Compared to the patients with no FI, the patients who reported FI symptoms were more often anti-centromere positive and had lower Body Mass Index (Table 1 and Figure 1A). We found that "severe" FI associated with Modified Rodnan Skin Score (Figure 1B), while recurrent FI episodes associated with digital ulcers (DU), loose stools and diarrhea (Figure 1C). Age and disease duration predicted FI worsening over time in all and the severe FI patients (Figure 1D), with no associations between baseline FI severity and score changes in either cohort. The FIQL subdomains, particularly coping (r=-0.74, p<.001) and embarrassment (r=-0.63, p<.001), correlated with both mild and moderate to severe UCLA fecal soilage scores, notably in "severe" FI patients. No correlation was found between FIQL subdomains and ScleroID lower GI domain and no other patient-reported outcome measures correlated with the severity of fecal soilage. Conclusion: In SSc patients with moderate to severe lower GI disease, reported prevalence of fecal incontinence symptoms is high. In this study, the FIQL scale identified more FI cases than the UCLA GIT score, probably indicating higher sensitivity of the FIQL scale. Recurrent FI episodes are associated with more severe SSc-related GI involvement. Although we have identified significant associations with various aspects of FI, early FI assessment appears key to prevent the considerable life restrictions patients face daily. REFERENCES: [1] Hoffmann-Vold AM, Fretheim HH, Sarna VK, Barua I, Carstens MN, Distler O, et al. Safety and efficacy of faecal microbiota transplantation by Anaerobic Cultivated Human Intestinal Microbiome (ACHIM) in patients with systemic sclerosis: study protocol for the randomised controlled phase II ReSScue trial. BMJ Open. 2021 Jun;11(6): e048541. Acknowledgements: NIL. Disclosure of Interests: Cristina Nita: None declared, Håvard Fretheim Boehringer Ingelheim, Bayer, Torhild Garen: None declared, Imon Barua: None declared, Maylen N Carstens: None declared, Henriette Didriksen: None declared, Vikas K. Sarna: None declared, Knut EA Lundin Takeda and Thermofisher, Takeda, Topas, Chugai, Alimentiv and GSK, Oliver Distler Boehringer Ingelheim, Janssen, Medscape, CITUS AG, 4P-Pharma, Abbvie, Acceleron, Alcimed, Altavant, Amgen, AnaMar, Argenx, Arxx, AstraZeneca, Blade, Bayer, Boehringer Ingelheim, Corbus, CSL Behring, Galderma, Galapagos, Glenmark, Gossamer, Horizon, Janssen, Kymera, Lupin, Medscape, Merck, Miltenyi Biotec, Mitsubishi Tanabe, Novartis, Orion, Prometheus, Redxpharma, Roivant, Topadur and UCB., Dinesh Khanna: None declared, Elizabeth Volkmann Boehringer Ingelheim, GSK, Boehringer Ingelheim, Prometheus, Horizon, Øyvind Midtvedt: None declared, Tore Midtvedt: None declared, Alvilde Dhainaut: None declared, Anna-Kristine H Halse: None declared, Gunnstein Bakland: None declared, Inge C. Olsen: None declared, Maiju E Pesonen: None declared, Øyvind Molberg: None declared, Anna-Maria Hoffmann-Vold Boehringer Ingelheim, Boehringer Ingelheim, Janssen, Medscape, Merck Sharp & Dohme, Novartis and Roche, ARXX, BMS, Boehringer Ingelheim, Genentech, Janssen, Medscape, Merck Sharp & Dohme and Roche, Boehringer Ingelheim, Janssen.

Background: The use of fecal microbiota transplantation (FMT) in systemic sclerosis (SSc) is an area of active investigation. The 20-week multicenter, randomized ReSScue trial [1] did not show efficacy of FMT by standard 'Anaerobic Cultivated Human Intestinal Microbiota' (ACHIM) on primary outcome (diarrhea or bloating), but the exploratory endpoint, impact of FMT on fecal incontinence (FI) symptoms, has not been assessed. Objectives: To evaluate the efficacy of FMT on FI in the randomized ReSScue trial. Methods: 67 SSc patients were randomly assigned to either placebo (n=34) or ACHIM treatment (n=33). The primary outcome and FI symptoms were assessed using the University of California Los Angeles Scleroderma Clinical Trial Consortium GIT 2.0 (UCLA GIT) at every visit. The Bristol Stool Form Scale assessed stool consistency at baseline and week 12. The impact of FI symptoms on quality of life was gauged using the Fecal Incontinence Quality of Life (FIQL) scale. One-way repeated measure analysis explored the behavior of FI symptoms over time. Changes meeting the minimally clinically important difference (MCID) threshold at week 20 were considered meaningful [2,3]. Effect size was calculated by Cohen's index (0.2 = small, 0.5 = moderate, 0.8 = large). Analyses were conducted for all patients, and a subset who reported FI at all time points (baseline, 12 and 20 weeks) and were defined as the "severe FI" cohort. Results: At baseline, 48 patients reported symptoms of FI with 24 in each treatment arm. The "severe FI" cohort included 14 patients, 8 in the ACHIM group and 6 in the placebo group. FMT-treated FI patients exhibited shorter disease duration and higher total UCLA GIT scores than placebo-FI patients (Table 1). At week 20, FMT-treated patients showed numerically improved UCLA fecal soilage scores, surpassing the MCID thresholds of "somewhat better" compared to the placebo group (Figure 1A,1C). Furthermore, the subset characterized by "severe FI" sustained improvement from 12 to 20 weeks (Figure 1B, 1C). Fewer FMT-treated patients reported loose stool at week 12, specifically 3 out of the initial 9 in the entire cohort and 6 in the "severe FI" cohort. In contrast, the placebo group had an additional two patients reporting watery stool. Over 20-weeks, despite reported changes in FI and stool consistency, patients did not perceive a corresponding improvement in their quality of life, consistently rating themselves as "about the same" on the FIQL scale. Conclusion: While the ReSScue trial showed no efficacy of FMT on bloating and diarrhea in SSc patients, the current analyses show that FMT significantly relieved FI symptoms, with consistent improvement over 20 weeks. A possible explanation might be the improved stool consistency leading to a decreased frequency of bowel loss. However, the positive results should be interpreted with caution given the wide 95% confidence intervals, limited number of participants, and short study duration. REFERENCES: [1] Hoffmann-Vold AM, Fretheim HH, Sarna VK, Barua I, Carstens MN, Distler O, et al. Safety and efficacy of faecal microbiota transplantation by Anaerobic Cultivated Human Intestinal Microbiome (ACHIM) in patients with systemic sclerosis: study protocol for the randomised controlled phase II ReSScue trial. BMJ Open. 2021 Jun;11(6): e048541. [2] Khanna D, Hays RD, Maranian P, Seibold JR, Impens A, Mayes MD, et al. Reliability and validity of the university of california, los angeles scleroderma clinical trial consortium gastrointestinal tract instrument. Arthritis Rheum. 2009 Sep 15;61(9):1257–63. [3] 'T Hoen LA, Utomo E, Schouten WR, Blok BFM, Korfage IJ. The fecal incontinence quality of life scale (FIQL) and fecal incontinence severity index (FISI): Validation of the Dutch versions. Neurourology and Urodynamics. 2017 Mar;36(3):710–5. Acknowledgements: NIL. Disclosure of Interests: Cristina Nita: None declared, Håvard Fretheim Boehringer Ingelheim, Bayer, Torhild Garen: None declared, Imon Barua: None declared, Maylen N Carstens: None declared, Henriette Didriksen: None declared, Vikas K. Sarna: None declared, Knut EA Lundin Takeda and Thermofisher, Takeda, Topas, Chugai, Alimentiv and GSK, Oliver Distler Boehringer Ingelheim, Janssen, Medscape, CITUS AG, 4P-Pharma, Abbvie, Acceleron, Alcimed, Altavant, Amgen, AnaMar, Argenx, Arxx, AstraZeneca, Blade, Bayer, Boehringer Ingelheim, Corbus, CSL Behring, Galderma, Galapagos, Glenmark, Gossamer, Horizon, Janssen, Kymera, Lupin, Medscape, Merck, Miltenyi Biotec, Mitsubishi Tanabe, Novartis, Orion, Prometheus, Redxpharma, Roivant, Topadur and UCB, Dinesh Khanna: None declared, Elizabeth Volkmann Boehringer Ingelheim, GSK, Boehringer Ingelheim, Prometheus, Horizon, Øyvind Midtvedt: None declared, Tore Midtvedt: None declared, Alvilde Dhainaut: None declared, Anna-Kristine H Halse: None declared, Gunnstein Bakland: None declared, Inge C. Olsen: None declared, Maiju E Pesonen: None declared, Øyvind Molberg: None declared, Anna-Maria Hoffmann-Vold Boehringer Ingelheim, Boehringer Ingelheim, Janssen, Medscape, Merck Sharp & Dohme, Novartis and Roche, ARXX, BMS, Boehringer Ingelheim, Genentech, Janssen, Medscape, Merck Sharp & Dohme and Roche, Boehringer Ingelheim, Janssen.