Case 1: a 74-year-old Japanese woman at the time of starting tocilizumab treatment
The patient had joint pain and swelling in 2003. She was diagnosed with RA and treated with disease-modifying antirheumatic drugs (DMARDs). In 2015, the right wrist joint was swollen and tender, and the CRP level increased to 2.83 mg/dl (normal value < 0.3 mg/dl). Although she received treatment for RA with methotrexate (MTX), salazosulfapyridine (SASP), and steroids, her arthritis was poorly controlled. In December 2015, because her arthritis worsened, she visited our hospital. Scleroderma from the fingers to the forearms was also observed at the first visit.
Anti-nuclear antibody (ANA) was 1280× (centromere), anti-cyclic citrullinated peptide antibody (ACPA) was 150 U/ml (normal value ≤4.5 U/ml), rheumatoid factor (RF) was 52 IU/ml (normal value ≤15 IU/ml), and anti-centromere antibody was 17.8 IU/ml (normal value ≤7.0 U/ml); all of them were elevated, but antibodies against topoisomerase I and U1-RNP were negative. The skin sclerosis developed from her fingers and expanded to her forearms, face, and feet. Chest computed tomography (CT) showed slight interstitial lung disease in the bilateral lower lung areas. The patient met the classification criteria for SSc established by the ACR/EULAR criteria in 2013 [6]. The patient was diagnosed with overlap syndrome involving RA and SSc. Larsen grade 3 was observed on both wrist and ankle X-rays, and grade 4 was observed on the left elbow X-ray. The 28-joint disease activity score with erythrocyte sedimentation rate (DAS28-ESR) and the clinical disease activity index (CDAI) were high, at 5.66 and 31.8, respectively. The modified Rodnan total skin thickness score (mRSS) was 23.
Both the RA and SSc were judged to be active, and it was decided to treat the patient with TCZ, 162 mg every 2 weeks. Administration of steroid (prednisolone 5 mg/day) and DMARDs (MTX 6 mg/week and SASP 1000 mg/day) was continued (Fig. 1a). During the 18-month period of TCZ therapy, TCZ was well tolerated, and the patient experienced general improvement in normal daily activities. At 18 months, the patient global assessment improved by 71 (75 to 4), the DAS28-ESR decreased from 5.66 to 1.10, the CDAI decreased from 31.8 to 5.5, and skin thickness evaluated with the mRSS improved from 23 to 3 (Fig. 1a). Reductions of both RA disease activity and of mRSS were seen.
There were no remarkable adverse events. Interstitial pneumonia did not change during the treatment period.
Case 2: a 65-year-old Japanese woman at the time of starting tocilizumab treatment
This patient with a history of RA diagnosed at 27 years of age underwent right wrist arthroplasty. After arthroplasty, she had been receiving sodium gold thiomalate (Shiosol®) for 7 years, which relieved her joint symptoms. However, she abruptly stopped outpatient visits, and was lost to follow-up.
In 2010, she was affected by joint pain, swelling and scleroderma of the palms, and visited our hospital again. The skin sclerosis developed from her fingers and expanded to her forearms, face, and feet. The findings of her right forearm skin biopsy were found to be consistent with SSc. She was diagnosed with overlap syndrome involving RA and SSc. She received treatment with cyclosporine, SASP, and steroids for RA and SSc treatment. Though an initial response was seen, the arthritis worsened. In 2016, both wrist joints were swollen and tender, and the CRP level increased to 1.05 mg/dl (normal value < 0.3 mg/dl). Larsen grade 3 was observed on wrist X-rays. A CT study showed patchy infiltrates associated with ground-glass opacities in the bilateral lower lung areas. ANA was 320× (homogeneous), ACPA was 151 U/ml (normal value ≤4.5 U/ml), RF was 229 IU/ml (normal value ≤15 IU/ml), and anti-topoisomerase I antibody was 88.7 U/ml (normal value ≤7.0 U/ml); all of them were increased, but antibodies against centromere and U1-RNP were negative. DAS28-ESR and CDAI were high, at 7.14 and 34.6, respectively. Skin sclerosis developed from her fingers to her forearms and face, and the mRSS was 15.
Both the RA and SSc were judged to be active, and it was decided to treat the patient with TCZ, 162 mg every 2 weeks. Administration of steroid (7 mg/day) and a DMARD (cyclosporine 150 mg/day) was continued (Fig. 1b). During the 18-month period of TCZ therapy, both RA disease activity and mRSS decreased. At 18 months, the patient global assessment improved by 32 (68 to 36), RA disease activity decreased (DAS28-ESR decreased from 7.14 to 3.70; CDAI decreased from 34.6 to 8.4), and skin thickness evaluated with the mRSS improved from 15 to 7 (Fig. 1b).
Interstitial pneumonia did not change during the treatment period. This patient developed cellulitis in the right foot plantar region at 6 weeks of treatment as an adverse reaction. TCZ was withdrawn for 4 weeks, but after the cellulitis resolved, she continued TCZ treatment.