Successful long-term systemic sclerosis treatment by high-frequent low-dose B cell-depleting therapy.

OBJECTIVES: Systemic sclerosis (SSc) is a multiorgan disease with a 10-year mortality rate of up to 50 %. B cell-depleting therapy with rituximab (RTX) appears effective in SSc treatment, but data from randomized controlled trials (RCTs) are lacking, and the frequency and dosage of RTX in SSc have no consensus. We aimed to evaluate the long-term efficacy and safety of quarterly RTX administration in SSc. METHODS: This study retrospectively analyzed 40 patients with SSC treated with RTX twice within 14 days every 3 months from 2010 to 2020. The patients fulfilled the LeRoy and the American College of Rheumatology/European League Against Rheumatism Criteria for SSc. Modified Rodnan skin score (mRSS), lung function test results, and serum immunoglobulin (IgG, IgA, and IgM) concentrations were analyzed. RESULTS: A total of 40 patients with SSc received RTX over a median time of 3.9 years (range: 1-10 years). The median mRSS (baseline: 19, 24 months: 16, p < 0.001) demonstrated a significant improvement, and the predicted forced vital capacity was stable. No new or unexpected safety signals, especially regarding treatment-related infectious adverse events, were observed. Immunoglobulin concentrations were within normal range, and specific antibodies to pneumococcal polysaccharides were preserved despite long-term B cell-depleting therapy. None of the patients died during the observation period of up to 10 years. CONCLUSION: SSc was effectively and safely treated with low-dose RTX quarterly. RCTs are warranted to validate the advantage of continuous B cell depletion by quarterly low-dose RTX administration compared to other treatment intervals.

Microstructural analysis of subchondral bone in knee osteoarthritis.

The results of this study show increased formation of bone in the subchondral areas in advanced stages of osteoarthritis of the knee. These changes seem to be influenced by mechanical factors. INTRODUCTION: Subchondral bone changes seem to contribute to the progression of knee osteoarthritis (OA). This study aimed to analyze subchondral bone microstructure in specimens of late-stage knee OA in respect to articular cartilage damage, meniscus integrity, and knee joint alignment. METHODS: Thirty proximal tibiae of 30 patients (20 female and 10 male) with late-stage OA retrieved during total knee arthroplasty were scanned using a high-resolution micro-computed tomography. The scans were semi-automatically segmented into five volumes of interest. The volumes of interest were then further analyzed using commercially available software. The degree of articular cartilage damage was assessed semi-quantitatively by magnetic resonance imaging before surgery. RESULTS: The mean bone fraction volume (bone volume/total volume (BV/TV)) in all weight-bearing locations was significantly higher compared to the non-weight-bearing reference point below the anterior cruciate ligament (p = 0.000). The mean BV/TV in the medial compartment was significantly higher compared to the lateral compartment (p = 0.007). As for the BV/TV in intact menisci, there was a significantly lower subchondral bone fraction volume compared to subluxated or luxated menisci in the medial (p = 0.020) and lateral compartment (p = 0.005). Varus alignment had a significantly higher subchondral BV/TV in the medial compartment, whereas valgus alignment had a significantly higher subchondral BV/TV in the lateral compartment (p = 0.011). CONCLUSIONS: The results show significant differences of subchondral bone microstructural parameters in respect to cartilage damage, meniscus' structural integrity, and knee joint alignment. Therefore, subchondral bone changes seem to be a secondary process in the late-stage OA of the knee caused by mechanical changes.