Background/Purpose: Even though 40 years have passed since MCTD was defined as a distinct disorder, there is still no evidence based therapy available. The choice of treatment is based on data from related connective tissue diseases. Biological agents have been used in a few patients with disease resistant to conventional immune-modulating drugs. Tumor necrosis factor alpha (TNFα) inhibitors have had limited efficacy and/or adverse effects (1, 2). B cell depletion therapy with rituximab (RTX) has only been reported in three MCTD patients, two of these responded to the treatment (3, 4), whereas the last had a treatment related  complications (5). 

Methods: A retrospective chart review of all the MCTD patients who were treated with RTX at the Rheumatology unit at the Oslo University Hospital from the 1st of June 2006 to the 15th of June 2012 and fulfilled at least one of the four MCTD criteria sets (Kasukawa’s, Alarcón-Segovia’s, Kahn’s and/or Sharp’s criteria) were performed. 

Results: Four female MCTD patients, all fulfilling all the four MCTD criteria sets, were treated with RTX according to the rheumatoid arthritis protocol with two 1,000 mg RTX infusions two weeks apart. Two of these patients were retreated with RTX after 10 and 21 months. At the start of the RTX treatment, the patient’s mean age was 44 years (37 to 65) and their mean disease duration was 8.7 (5 to 12) years. The mean observation time was 46 (23 to 70) months. So far, no adverse effects have been identified

Patient details;
Patient 1: Therapy resistant thrombocytopenia over years. Normalization of platelets 15 weeks after RTX and currently uses low dose prednisolone (GC).
Patient 2: Therapy resistant myositis with high serum creatinine kinase (CK, max 4605 U/L); reduced proximal muscle strength and increased signal intensity on MRI (STIR and T1).
After RTX, normalization of CK and reduced MRI changes and was able to reduce GC dose.  She had two minor relapses, the first 12 months after RTX and is currently treated with methotrexate (MTX) and low dose GC.
Patient 3: Therapy resistant myositis with; high CK (max 7076 U/L); MRI changes and reduced muscle strength. Two courses of RTX, ten months apart, with the background of MTX, GC, Hydroxychloroquine (HCQ) led to normalization of CK and increased muscle strength.
Patient 4: MCTD/RA overlap, therapy resistant, destructive arthritis. Non-responder to two TNFα-inhibitors. RTX with a background therapy of MTX, GC & HCQ, led to a complete remission of arthritis and significant relief in Raynaud’s phenomenon for 18 months. A recent relapse was treated with a new round of rituximab.

Conclusion:

During the observation period, four MCTD patients received B cell depletion therapy with RTX. The treatment was well tolerated and had significant clinical effects on thrombocytopenia, myositis and arthritis. Randomized controlled trials are needed to further evaluate the effects of RTX in MCTD. 

References:
1. Richez C et al. Clin Exp Rheumatol. 2005;23(2):273
2. Christopher-Stine L et al. J Rheumatol. 2003;30(12):2725-7
3. Haroon M et al. Rheumatology (Oxford). 2007;46(4):718-9
4. Rudolph SE et al. Dtsch Med Wochenschr. 2009;134(36):1734-8
5. Vela P et al.  Lupus. 2010;19(8):1005-6

ACR Meeting Abstracts - https://acrabstracts.org/abstract/evaluating-the-therapeutic-effects-of-b-cell-depletion-therapy-with-rituximab-in-a-longitudinal-cohort-of-mixed-connective-tissue-disease-patients/