TNF inhibitor treatment is associated with a lower risk of hand osteoarthritis progression in rheumatoid arthritis patients after 10 years

Loef, M.; Kroon, Féline P B; Bergstra, Sytske Anne; Pol, J.A. van der; Lems, Willem F.; Kerstens, P.; Allaart, Cornelia F; Kloppenburg, Margreet

doi:10.1093/rheumatology/key016

Cited by 16 publications

(12 citation statements)

References 31 publications

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“…Therefore, it is imperative to identify an important indicator of the severity of the disease through examining the expression level of inflammatory cytokines. For instance, previous researches have shown that tumour necrosis factor (TNF‐α) and interleukin (IL)‐1β are the main components of inflammation in RA . However, the current treatment of RA remains expensive, especially the costs of biological agents, surgery and rehabilitation treatment , and hence exploration for the molecular mechanism of RA is still essential to minimize the clinical and socioeconomic impacts of RA.…”

Section: Introductionmentioning

confidence: 99%

Imatinib inhibits CSF1R that stimulates proliferation of rheumatoid arthritis fibroblast-like synoviocytes

Tang

Peng

et al. 2018

Clinical and Experimental Immunology

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Summary In this study, we aimed to explore the effects of imatinib on the proliferation of rheumatoid arthritis synovial cell (RA‐FLS) and inflammatory responses by regulating CSF1R. Differential genes were screened via microarray analysis, followed by being analysed through the weighted co‐expression network (WGCNA) network, that included module and cluster analysis. The relationship between imatinib and genes was visualized using the Search Tool for the Retrieval of Interacting Genes (STITCH) database. Expressions of mRNA and protein were determined by reverse transcription–polymerase chain reaction (RT–PCR) and Western blot, respectively. Cell viability was examined via clone formation assay, while cell cycle and apoptosis were analysed through flow cytometry analysis. The hub gene CSF1R was ultimately determined by microarray analysis and WGCNA analysis. Colony‐stimulating‐factor receptor‐1 (SF1R) was highly expressed in rheumatoid arthritis tissues and cells, and CSF1R over‐expression could promote inflammatory responses. Moreover, CSF1R could promote RA‐FLS proliferation, inhibit apoptosis and accelerate the cell cycle. The targeting relationship between imatinib and CSF1R was also validated in this study. Imatinib attenuated RA‐FLS inflammation in a concentration‐dependent manner. Meanwhile, imatinib could inhibit RA‐FLS proliferation and promote apoptosis, ultimately reducing the damage of RA‐FLS. Over‐expression of CSF1R accelerated the cell cycle and proliferation of RA‐FLS, while inhibiting cell apoptosis. Conversely, imatinib could significantly restrain the cell cycle and viability of RA‐FLS and accelerated apoptosis via suppression of CSF1R expression. Further, histological and serological assay investigated and proved the proinflammatory effects of CSF1R in RA rabbits.

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Section: Introductionmentioning

confidence: 99%

Imatinib inhibits CSF1R that stimulates proliferation of rheumatoid arthritis fibroblast-like synoviocytes

Tang

Peng

et al. 2018

Clinical and Experimental Immunology

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“…Presumably, tackling inflammatory mechanisms appears to be helpful here, not only suggested by the short-term treatment success of glucocorticoids, 5 but also by the interesting finding that tumour necrosis factor inhibitor treatment is associated with a lower risk of hand OA progression in patients with RA. 23 A previous study, the digital osteoarthritis in refractory hand OA-study (DORA), evaluating adalimumab in patients with refractory hand OA, failed to demonstrate any clinical 50% improvement after 6 weeks. There were also no statistically significant differences for any of the secondary outcomes (number of painful joints and of swollen joints, morning stiffness, patient global assessments, functional index for hand OA and consumption of analgesics).…”

Section: Osteoarthritis Osteoarthritis Osteoarthritismentioning

confidence: 97%

Hydroxychloroquine in patients with inflammatory and erosive osteoarthritis of the hands: results of the OA-TREAT study—a randomised, double-blind, placebo-controlled, multicentre, investigator-initiated trial

et al. 2021

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ObjectivesHand osteoarthritis (OA) is a condition characterised by cartilage degradation and frequently erosive changes. Analgesics and non-steroidal anti-inflammatory drugs are used for symptomatic relief but are often poorly tolerated or contraindicated. Previous publications suggest hydroxychloroquine (HCQ) as a possible treatment for hand OA. The OA-TREAT study aimed to investigate the efficacy and safety of HCQ in patients with inflammatory and erosive hand OA (EOA).MethodsOA-TREAT was an investigator-initiated, multicentre, randomised, double-blind, placebo (PBO)-controlled trial. Patients with inflammatory and EOA, according to the ACR criteria, with radiographically erosive disease were randomised 1:1 to HCQ 200–400 mg/day or PBO for 52 weeks (W52). Both groups received stable standard therapy. The primary endpoint was Australian Canadian Hand Osteoarthritis Index (AUSCAN) for pain and hand disability at W52.Results75 patients were randomised to HCQ and 78 to PBO. At W52, mean AUSCAN pain was 26.7 in HCQ and 26.5 in PBO patients (p=0.92). Hand disability measured by AUSCAN function (mean) was 48.1 in HCQ and 51.3 in PBO patients (p=0.36). Changes in radiographic scores did not differ significantly (p>0.05) between treatment groups. There were 7 serious adverse events in the HCQ and 15 in the PBO group.ConclusionsOA-TREAT is the first large randomised PBO controlled trial focusing on EOA. HCQ was no more effective than PBO for changes in pain, function and radiographic scores in the 52-week period. Overall safety findings were consistent with the known profile of HCQ.

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“…TNF inhibition has also been investigated using IgG monoclonal antibodies (infliximab or adalimumab) or circulating receptor fusion protein (etanercept). Treatment with anti-TNF-α blockers has demonstrated a decrease in disease progression but not in symptoms in patients with hand OA ( Verbruggen et al, 2012 ; Kloppenburg et al, 2018 ; Loef et al, 2018 ).…”

Section: Current and Future Pharmaceutical Therapy For Oamentioning

confidence: 99%

Immunological Events, Emerging Pharmaceutical Treatments and Therapeutic Potential of Balneotherapy on Osteoarthritis

et al. 2021

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TNF inhibitor treatment is associated with a lower risk of hand osteoarthritis progression in rheumatoid arthritis patients after 10 years

Abstract: TNFi treatment was associated with a reduced risk on radiographic hand OA progression in DIP joints but not in PIP joints after 10 years. Although the effect sizes are small, these results provide evidence for influence of TNF-α in hand OA pathogenesis.

Cited by 16 publications

References 31 publications

Imatinib inhibits CSF1R that stimulates proliferation of rheumatoid arthritis fibroblast-like synoviocytes

Imatinib inhibits CSF1R that stimulates proliferation of rheumatoid arthritis fibroblast-like synoviocytes

Hydroxychloroquine in patients with inflammatory and erosive osteoarthritis of the hands: results of the OA-TREAT study—a randomised, double-blind, placebo-controlled, multicentre, investigator-initiated trial

Immunological Events, Emerging Pharmaceutical Treatments and Therapeutic Potential of Balneotherapy on Osteoarthritis

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