Variability in clinical and biological response to rituximab in autoimmune diseases: an opportunity for personalized therapy?

Reddy, Venkat; Leandro, Maria

doi:10.2217/ijr.14.18

Cited by 7 publications

(10 citation statements)

References 89 publications

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“…Repopulation of the peripheral blood occurs predominantly with naive mature and transitional B cells, similar to the situation after bone marrow transplantation. As previously reviewed, prolonged clinical response in RA and in SLE seems to be associated with delayed reconstitution of peripheral blood CD27 + memory B cells, whereas shorter responses correlates with repopulation with higher levels of memory B cells 35 .…”

Section: Response To Treatmentmentioning

confidence: 90%

“…It is recognized that even effective depletion as measured in peripheral blood does not always correlate with clinical response 37 . As previously suggested by our group, to understand these discrepancies better it is important to distinguish inadequate clinical response despite effective depletion as "refractory disease", and not achieving effective depletion as "rituximab resistance" 35 . The latter could be explained by insufficient dose or increased drug clearance, but also to resistance of B-cell clones to depletion mechanisms induced by rituximab.…”

Section: Rituximab Resistance Vs Refractory Diseasementioning

confidence: 96%

“…The response to B-cell depletion is remarkably variable between patients with SLE, with respect to the degree and duration of BCD, clinical response, duration of remission and relapse 35 . Treatment with rituximab is associated with a reduction in anti-dsDNA and anti-nucleosome antibody levels, but no change is seen in anti-ENA antibodies 36 .…”

Section: Rituximab In Slementioning

confidence: 99%

“…These important concepts led us to hypothesize that patients who do not achieve clinical response but are effectively depleted ("refractory disease") and who do not reveal any evidence of early repopulation may not benefit from further B-cell targeted therapies. In contrast, at least some patients from the group with poor clinical response who did not achieve effective sustained depletion ("rituximab resistance") may benefit from other B-cell depletion agents or treatment regimens 35 .…”

Section: Rituximab Resistance Vs Refractory Diseasementioning

confidence: 99%

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Improving B-cell depletion in systemic lupus erythematosus and rheumatoid arthritis

Mota

Reddy

Isenberg

2016

Expert Review of Clinical Immunology

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Rituximab-based B-cell depletion (BCD) therapy is effective in refractory rheumatoid arthritis (RA) and although used to treat patients with refractory systemic lupus erythematosus (SLE) in routine clinical practice, rituximab failed to meet the primary endpoints in two large randomised controlled trials (RCTs) of non-renal (EXPLORER) and renal (LUNAR) SLE. Areas covered: We review how BCD could be improved to achieve better clinical responses in RA and SLE. Insights into the variability in clinical response to BCD in RA and SLE may help develop new therapeutic strategies. To this end, a literature search was performed using the following terms: rheumatoid arthritis, systemic erythematosus lupus, rituximab and B-cell depletion. Expert commentary: Poor trial design may have, at least partly, contributed to the apparent lack of response to BCD in the two RCTs of patients with SLE. Enhanced B-cell depletion and/or sequential therapy with belimumab may improve clinical response at least in some patients with SLE.

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Section: Response To Treatmentmentioning

confidence: 90%

Section: Rituximab Resistance Vs Refractory Diseasementioning

confidence: 96%

Section: Rituximab In Slementioning

confidence: 99%

Section: Rituximab Resistance Vs Refractory Diseasementioning

confidence: 99%

See 2 more Smart Citations

Improving B-cell depletion in systemic lupus erythematosus and rheumatoid arthritis

Mota

Reddy

Isenberg

2016

Expert Review of Clinical Immunology

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“…Поэтому подходы к выбору оптимальной дозы РТМ при РА требует дальнейшего изу-чения в рамках проблемы персонифицированной терапии этого заболевания [51]. В то же время необходимо прини-мать во внимание дозозависимые НЯ на фоне лечения РТМ, такие как поздняя нейтропения [52] и гипогаммагло-булимнемия [53].…”

Section: таблицаunclassified

The Efficacy and Safety of Rituximab Biosimilar (Acellbia®) in Rheumatoid Arthritis as the First Biological Agent: Results of Phase Iii (Alterra) Clinical Trial

Nasonov

Мазуров

Зонова

et al. 2017

Naučno-praktičeskaâ revmatologiâ

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The Russian biotechnological company «BIOCAD» has designed a chimeric monoclonal antibody against CD20 (BCD-020, Acellbia®) that is a biosimilar of rituximab (RTM; MabThera®, F. Hoffmann-La Roche Ltd., Switzerland). In recent years, there has been evidence that RTM can be used at lower doses than those given in the standard recommendations and instructions for the use of this drug. This serves as the basis for the BCD-020-4/ALTERRA (ALTErnative Rituximab regimen in Rheumatoid Arthritis) trial, the objective of which was to investigate the efficiency and safety of using Acellbia® (at a dose of 600 mg twice at a 2-week interval) as the first biological agent (BA) for methotrexate (MTX)-resistant active rheumatoid arthritis (RA). The investigation enrolled 159 patients aged 18 to 80 years with active RA. After 24 weeks 65.7 and 29.4% of patients achieved 20% improvement by the American College of Rheumatology (ACR) criteria in the Acellbia® + MTX and placebo (PL) + MTX groups, respectively (p<0.0001). The differences in the ACR20 response rate in the two groups were 36.3% (95% CI, 19.27–53.28%). There were significant differences between the groups in the ACR50 response rates: 28.4% and 5.9% (p=0.001) and in the ACR70 ones: 12.8% and only 2.0%, respectively (p=0.036). Analysis of all recorded adverse events (AE) frequency showed no significant differences between the patients in the study and control groups and demonstrates its equivalence with that of RTM (MabThera®); all the AE were expectable. It is noted that antibodies to RTM with binding and neutralizing activities had no impact on the efficiency and safety of therapy.

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Effect of Rituximab on Serum Levels of Anti-C1q and Antineutrophil Cytoplasmic Autoantibodies in Refractory Severe Lupus Nephritis

Zhang

Zhao

2014

Cell Biochem Biophys

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The objective of this study was to analyze and compare the effects of rituximab (RTX) and cyclophosphamide (CTX) on the serum levels of anti-C1q antibodies and antineutrophil cytoplasmic autoantibodies (ANCA) in assessing the prognosis of severe and refractory lupus nephritis (LN). Eighty-four cases of severe and refractory LN were randomly divided into two groups of 42 cases each: CTX group and RTX group (CTX+RTX) during February 2010 to February 2014 in our hospital. Changes in serum levels of anti-C1q antibodies and ANCA in the two groups were examined, and efficacies of the drugs were compared. The total efficacy of RTX group was found to be 83.3 %, which was significantly higher than that of the CTX group, 57.1 % (p < 0.05). The serum anti-C1q antibodies and ANCA were decreased to 11.9 and 26.2 % in the RTX-treated group, which was significantly lower than those observed in the CTX-treated patients (21.4 and 69.0 % respectively) (p < 0.05). The clinical indices of LN were significantly improved in the two groups after the treatment. However, the urinary protein, albumin, complement C3, the percentage of CD19(+)B cells, and SLEDAI scores in the RTX group were significantly lower than those in the CTX group (p < 0.05). RTX plus with CTX showed a better therapeutic efficacy compared to CTX, and it significantly improved the prognosis of refractory and severe LN. The improvement in disease prognosis was directly related to the reduced serum levels of anti-C1q and ANCA measured during the course of treatment suggesting that they can serve to be valuable biomarkers of LN prognosis. Moreover, the measurement can assist in the judgment of RTX efficacy guiding the adjustment of the drug dose to improve the quality of life.

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Variability in clinical and biological response to rituximab in autoimmune diseases: an opportunity for personalized therapy?

Cited by 7 publications

References 89 publications

Improving B-cell depletion in systemic lupus erythematosus and rheumatoid arthritis

Improving B-cell depletion in systemic lupus erythematosus and rheumatoid arthritis

The Efficacy and Safety of Rituximab Biosimilar (Acellbia®) in Rheumatoid Arthritis as the First Biological Agent: Results of Phase Iii (Alterra) Clinical Trial

Effect of Rituximab on Serum Levels of Anti-C1q and Antineutrophil Cytoplasmic Autoantibodies in Refractory Severe Lupus Nephritis

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