Rituximab for Gout

Overseen By John FitzGerald, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of California, Los Angeles

Must be taking: Rituximab, Methotrexate

Must not be taking: Steroids, Investigational drugs

Disqualifiers: Renal impairment, Heart failure, Cancer, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 35

9 Participants Needed

Trial Summary

What is the purpose of this trial?

This safety and feasibility, open-label study of up to 9 subjects will examine a group of subjects with poorly controlled tophaceous gout (intolerant to or ineffective oral urate lowering agents and loss of prior Pegloticase response) pre-treated with Rituximab to recapture response to Methotrexate-Pegloticase.

Do I need to stop my current medications for the trial?

Yes, you will need to stop taking any oral urate lowering therapy at least 7 days before the first Pegloticase infusion and remain off it during the Pegloticase infusions.

What data supports the effectiveness of the drug Rituximab for treating gout?

Rituximab has been shown to be effective in treating other conditions like hepatitis C-associated cryoglobulinemic vasculitis and ANCA-associated vasculitis, where it helped achieve remission and had a good safety profile. This suggests it might also be beneficial for gout, although direct evidence for gout is not provided. ^{1 2 3 4 5}

Is rituximab generally safe for humans?

Rituximab has been used for over 10 years and is generally considered safe, but it can increase the risk of infections, especially in people with weakened immune systems. It is important to screen for hepatitis B before treatment, as rituximab can reactivate this virus, leading to serious liver problems. Some studies also suggest a possible link to a rare brain infection called PML. ^{4 6 7 8 9}

How does the drug Rituximab differ from other treatments for gout?

Rituximab is unique because it targets the CD20 antigen on B cells, which is different from typical gout treatments that focus on reducing uric acid levels. This mechanism is more commonly used in treating autoimmune diseases and certain types of cancer, making its application in gout novel. ^{10 11 12 13 14}

Research Team

John FitzGerald, MD

Principal Investigator

University of California, Los Angeles

Eligibility Criteria

This trial is for people with severe gout who can't take or haven't had success with standard oral treatments and have stopped responding to Pegloticase. They'll be given Rituximab before restarting Methotrexate-Pegloticase therapy.

Inclusion Criteria

Meets the American College of Rheumatology Classification Criteria for Gout

I agree to stop my gout medication 7 days before starting Pegloticase treatment.

I stopped taking Pegloticase because it didn't work or caused a bad reaction.

Exclusion Criteria

Pregnant, planning to become pregnant, breastfeeding, or not on an effective form of birth control

Anaphylaxis or other prior severe infusion reaction to Pegloticase

Abnormal blood cell counts

Timeline

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

1 visit (in-person)

Rituximab Pre-Treatment

Rituximab 1000 mg administered at week -6 and week -4 via intravenous infusion over 5 hours

6 weeks

2 visits (in-person)

Methotrexate Treatment

Methotrexate 15 mg orally once weekly, started 4 weeks prior to Pegloticase initiation

6 weeks

4 visits (virtual)

Methotrexate-Pegloticase Study Treatment

Methotrexate administered weekly and Pegloticase coadministered every two weeks for up to 12 months

12 months

26 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 months

2 visits (phone)

Treatment Details

Interventions

• Rituximab

Trial Overview The study is testing if giving Rituximab, an immune system-modifying drug, before resuming a combination of Methotrexate and Pegloticase helps patients with tough-to-treat gout respond better to treatment.

Participant Groups

Group I: Rituximab Experimental Treatment 1 Intervention

Rituximab 1000 mg will be administered at week -6 and week -4 via intravenous infusion over the duration of 5 hours prior to the Pegloticase (Standard-of-Care) treatment.

Rituximab is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Rituxan for:

• Non-Hodgkin's lymphoma
• Chronic lymphocytic leukemia
• Rheumatoid arthritis
• Granulomatosis with polyangiitis
• Microscopic polyangiitis

Approved in European Union as MabThera for:

• Non-Hodgkin's lymphoma
• Chronic lymphocytic leukemia
• Rheumatoid arthritis
• Granulomatosis with polyangiitis
• Microscopic polyangiitis

Approved in Canada as Rituxan for:

• Non-Hodgkin's lymphoma
• Chronic lymphocytic leukemia
• Rheumatoid arthritis
• Granulomatosis with polyangiitis
• Microscopic polyangiitis

Who Is Running the Clinical Trial?

University of California, Los Angeles

Lead Sponsor

Trials

1,594

Recruited

10,430,000+

Findings from Research

Tocilizumab is an effective treatment option for rheumatoid arthritis in patients who have not responded to other therapies, but it is not more effective than rituximab in cases of multiple treatment failures, based on clinical evaluations of four placebo-controlled trials.

While tocilizumab offers convenience with intravenous administration every four weeks, it carries significant risks of serious infections and other adverse effects, and its long-term safety profile, particularly regarding cancer risk, remains uncertain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tocilizumab: new drug. Rheumatoid arthritis: another 'mab', no therapeutic advantage. [2016]

Rituximab has been shown to be very safe over more than 10 years of use, but it can significantly increase the risk of infections, especially in patients with low-grade lymphoma or severe immunodeficiency, such as those with HIV or on immunosuppressive therapies.

The most critical infection associated with rituximab is hepatitis B reactivation, which can lead to severe liver failure; therefore, screening for hepatitis B and considering preemptive antiviral treatment is essential for patient safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rituximab-associated infections. Gea-Banacloche, JC.[2020]

Rituximab (RTX) showed a high overall response rate of 61.3% in patients with refractory granulomatosis with polyangiitis (GPA), with complete remission achieved in 9.3% of cases, indicating its efficacy in treating this condition.

Granulomatous manifestations, particularly orbital masses, were more resistant to RTX treatment compared to vasculitic manifestations, with a significant difference in response rates (89.2% for renal disease vs. 44.4% for orbital masses), highlighting the need for tailored treatment approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rituximab for refractory granulomatosis with polyangiitis (Wegener's granulomatosis): comparison of efficacy in granulomatous versus vasculitic manifestations. Holle, JU., Dubrau, C., Herlyn, K., et al.[2022]

Rituximab is a genetically engineered monoclonal antibody that effectively targets CD20-positive B-cell malignancies, making it a key treatment for conditions like non-Hodgkin lymphoma and chronic lymphocytic leukemia.

While rituximab is effective for various B-cell related diseases, it carries significant risks, including severe infusion reactions and other serious side effects, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A review of rituximab in cutaneous medicine. Scheinfeld, N.[2020]

Rituximab is primarily indicated for refractory immune thrombocytopenic purpura and is considered the best treatment for cold agglutinin disease, but its long-term benefit-to-risk ratio remains uncertain, especially in relation to splenectomy.

While rituximab shows promise in treating various autoimmune diseases, including Wegener granulomatosis and HCV-associated cryoglobulinemia, there are significant risks of adverse events, particularly infections and severe reactions in certain patient populations, highlighting the need for further clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rituximab off label use for difficult-to-treat auto-immune diseases: reappraisal of benefits and risks. Sailler, L.[2022]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Therapeutic Potential of Rituximab in Managing Hepatitis C-Associated Cryoglobulinemic Vasculitis: A Systematic Review. [2023]

2. Germany pubmed.ncbi.nlm.nih.gov

[Rheumatic diseases with initial manifestations in middle age: gout, rheumatoid arthritis and ANCA-associated vasculitides]. [2021]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Treatment of severe renal disease in ANCA positive and negative small vessel vasculitis with rituximab. [2022]

4. France pubmed.ncbi.nlm.nih.gov

Tocilizumab: new drug. Rheumatoid arthritis: another 'mab', no therapeutic advantage. [2016]

5. England pubmed.ncbi.nlm.nih.gov

Single-dose rituximab for remission induction and maintenance therapy in ANCA-associated vasculitis: a retrospective analysis of 17 patients. [2015]

6. United States pubmed.ncbi.nlm.nih.gov

Rituximab-associated infections. [2020]

7. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of low-dose rituximab as induction therapy for antineutrophil cytoplasmic antibody-associated vasculitis with renal involvement: a Chinese case series. [2023]

8. Netherlands pubmed.ncbi.nlm.nih.gov

B-cell therapies in established rheumatoid arthritis. [2019]

9. Spain pubmed.ncbi.nlm.nih.gov

[Rituximab in rheumatoid arthritis: a systematic review of efficacy and safety]. [2018]

10. England pubmed.ncbi.nlm.nih.gov

Rituximab for refractory granulomatosis with polyangiitis (Wegener's granulomatosis): comparison of efficacy in granulomatous versus vasculitic manifestations. [2022]

11. United States pubmed.ncbi.nlm.nih.gov

A review of rituximab in cutaneous medicine. [2020]

12. England pubmed.ncbi.nlm.nih.gov

Treatment of refractory retrobulbar granuloma with rituximab in a patient with ANCA-negative Wegener's granulomatosis: a case report. [2016]

13. Germany pubmed.ncbi.nlm.nih.gov

[Recommendations on the use of rituximab for ANCA-associated vasculitis]. [2018]

14. United States pubmed.ncbi.nlm.nih.gov

Rituximab off label use for difficult-to-treat auto-immune diseases: reappraisal of benefits and risks. [2022]