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Innovations
Rituximab for treatment of ocular inflammatory disease: a series of four cases
  1. P A Kurz1,2,3,
  2. E B Suhler1,
  3. D Choi1,
  4. J T Rosenbaum1
  1. 1
    Casey Eye Institute/Oregon Health & Science University, Portland, Oregon, USA
  2. 2
    Dayton VA Medical Center, Dayton, Ohio, USA
  3. 3
    Ohio State University Department of Ophthalmology, Columbus, Ohio, USA
  1. Dr J T Rosenbaum, Mail Code L467AD, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA; rosenbaj{at}ohsu.edu

Abstract

Rituximab may be effective in the treatment of ocular inflammatory disease. Dosing is less frequent than many medications currently available. Four cases are reported, each of which appeared to have responded well to treatment with rituximab, although patient 2 was able to remain on a low dose of prednisone for only 2 months. The ongoing pilot study will hopefully provide additional insight into the benefit of rituximab for treatment of scleritis and idiopathic orbital inflammatory disease.

https://doi.org/10.1136/bjo.2007.133173

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    Rituximab (Rituxan), a genetically engineered, chimeric, monoclonal antibody that recognises CD20 on mature B lymphocytes, has demonstrated efficacy in the treatment of rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), thyroid-associated ophthalmopathy and Wegener granulomatosis (WG).1–8 One report also suggests benefit in refractory anterior uveitis.9 Rituximab is proposed to deplete CD20+ B cells by three mechanisms: antibody-dependent cellular cytotoxicity, complement-dependent cytotoxicity and apoptosis. Treatment with rituximab intravenously results in profound reduction in peripheral blood B lymphocytes for approximately 6 to 12 months, although longer periods of depletion can occur.10

    INNOVATION

    Patients with WG may develop orbital inflammation. Scleritis can be associated with RA, SLE and WG. Although the use of rituximab for ocular inflammatory disease has not been extensively studied, it seems reasonable to consider rituximab to treat these ocular inflammatory conditions. We report two cases of refractory scleritis and two cases of non-infectious orbital inflammation in which treatment with rituximab appeared beneficial.

    PATIENT 1

    A 57-year-old white male with a history of nodular scleritis failed treatment with non-steroidal anti-inflammatory drugs, azathioprine and mycophenolate mofetil (MMF) monotherapy. After treatment with rituximab, he tapered off prednisone. He remained quiet on MMF 1000 mg twice daily for 11 months before having a mild, unilateral flare that was promptly controlled with low-dose prednisone.

    Seventeen months following the rituximab infusions, he had a bilateral flare requiring prednisone 40 mg/day. Repeat treatment with rituximab induced remission and allowed prednisone tapering.

    PATIENT 2

    A 27-year-old female with diabetes, RA and bilateral anterior scleritis failed treatment with anakinra, methotrexate, hydroxychloroquine, etanercept, adalimumab, minocycline and leflunomide. Treatment with rituximab allowed her to taper prednisone to 30 mg every other day while continuing methotrexate 20 mg/week.

    Five months after receiving rituximab, she required retreatment for recurrent joint and eye symptoms. With continued methotrexate therapy, she tapered prednisone to 5 mg/day and remained quiet on this dose for 2 months before flaring following a hospital admission for hyperglycaemia.

    PATIENT 3

    A 29-year-old female with severe idiopathic orbital inflammation failed methotrexate, MMF and combination therapy with methotrexate and ciclosporin. She had only transient benefit with cyclophosphamide 1000 mg intravenous Q 3 weeks for 4 months before it was stopped after she had a rash with the last two infusions. Three to 4 months after treatment with rituximab, she stopped methotrexate due to nausea. She remained quiet off all medications for 1 year before having recurrent orbital inflammation which responded to reinstitution of oral methotrexate 15 mg/week.

    PATIENT 4

    A 30 year-old female with limited WG failed treatment with azathioprine, methotrexate and oral cyclophosphamide. She gained 23 kg on prednisone and had required treatment with intravenous methylprednisolone. The orbital disease continued to worsen despite prednisone 50 mg/day.

    Following rituximab, both sinus and orbital disease improved. With continued subcutaneous methotrexate therapy at 25 mg/week, prednisone was tapered to 6 mg/day.

    Four months following treatment with rituximab, she had increased nasal crusting requiring a small pulse of prednisone 20 mg/day which was tapered to 10 mg/day over 2 weeks and subsequently back to 6 mg/day.

    SIDE EFFECTS

    The most common side effects with rituximab are infusion-related symptoms, which usually occur with the first infusion, may vary in severity and are usually reversible with medical intervention. These symptoms may include a flu-like illness, fever, chills/rigors, urticaria, nausea, headache, bronchospasm, hypotension and angio-oedema. More severe manifestations which can even lead to death rarely include hypoxia, pulmonary infiltrates, myocardial infarction, ventricular fibrillation or other cardiac arrhythmias, cardiogenic shock, acute respiratory distress syndrome, acute renal failure requiring dialysis (in the setting of tumour lysis syndrome), severe mucocutaneous skin reactions, hepatitis B reactivation, progressive multifocal leucoencepalopathy, other opportunistic infections, abdominal pain, and bowel obstruction or perforation (when used in combination with chemotherapy in patients with diffuse large B cell lymphoma).

    All patients in our case series were pretreated with diphenhydramine 25–50 mg intravenous, acetaminophen and methylprednisolone 100 mg intravenous just before the infusion. Patients 1 and 2 noted itching with infusion. Patient 1 also noted anxiety with the infusion (perhaps related to the methylprednisolone). Patient 4 had nausea that was controlled with promethazine and rigors that responded to lorazepam and meperidine.

    CASE SERIES

    For patients 1–3, a treatment with rituximab consisted of 1 g intravenous twice, with a 2-week interval between doses (table 1). Patient 4 received 375 mg/m2 weekly for 4 weeks. A mixed-effects model was used to test the statistical significance of the difference in prednisone dose levels before and after rituximab therapy while accounting for potential correlations among repeated measures within a person.

    View this table:
    Table 1 Four patients’ responses

    LIMITATION

    The obvious limitation of this case series is the small sample size. However, as these inflammatory conditions are relatively uncommon, it is difficult to develop large randomised clinical trials dealing with inflammatory eye disease. Patients 1–3 received rituximab in a different dosing regimen than Patient 4. With a small sample size, it is unclear whether one dosing regimen is preferred over the other. We do not have data quantifying the B-lymphocyte count before and after treatment in these cases.

    POTENTIAL APPLICATION

    Rituximab may have a role in treatment of ocular inflammatory disease, including refractory scleritis and non-infectious orbital inflammatory disease. Continued investigation will help define this role.

    SUMMARY

    Rituximab may be effective in the treatment of ocular inflammatory disease. Dosing is less frequent than many medications currently available. We have reported four cases here, each of which appeared to have responded well to treatment with rituximab, although patient 2 was able to remain on a low dose of prednisone for only 2 months. Our ongoing pilot study will hopefully provide additional insight into the benefit of rituximab for treatment of scleritis and idiopathic orbital inflammatory disease.

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    Footnotes

    • Funding: We are grateful for financial support from the Stan and Madelle Rosenfeld Family Trust.

    • Competing interests: JTR, EBS and PAK disclose a relationship with Genentech, in that Genentech is sponsoring the follow-up Phase I/II prospective study.

    • Ethics approval: Ethics approval was provided by the Institutional Review Board, Oregon Health & Science University.

    • Patient consent: Obtained.