Use of a bDMARD or tsDMARD for the management of inflammatory arthritis under checkpoint inhibitors: an observational study.

OBJECTIVE: There is limited experience regarding the use of biological disease-modifying antirheumatic drug (bDMARD) and JAK inhibitor (JAKi) for the management of immune checkpoint inhibitors (ICI)-induced inflammatory arthritis. We aimed to assess their efficacy and safety in this setting. METHODS: Using the Club Rhumatismes and Inflammation French network, we conducted a multicentre, retrospective, observational study of patients with cancer diagnosed with inflammatory arthritis under ICI(s) and treated with bDMARD or JAKi. Clinical data were collected using a standardised case report form. RESULTS: Twenty patients (60% men, median age 69.5 years) were included, with rheumatoid arthritis (RA)-like (n=16), polymyalgia rheumatica-like (n=2) or psoriatic arthritis-like (n=2) clinical presentation. Two patients had pre-existing RA. 90% were treated with glucocorticoids as first-line therapy and 60% received methotrexate prior to bDMARD or JAKi. Anti-interleukin-6 receptor (IL-6R) therapy was used in 13/20 patients (65%), leading to clinical improvement in 11/13 patients (85%), but one patient experienced intestinal perforation and cancer progression was noticed in 6/13 patients (46%). Tumour necrosis factor inhibitors were used in 5/20 patients (25%), with improvement in 4/5 patients (80%) and cancer progression was observed in 3/5 patients (60%). Two infections (diverticulitis and pneumonitis) were reported. Anakinra, baricitinib and ustekinumab were each used in one patient. Median duration of the bDMARD or JAKi was 17 weeks. CONCLUSION: Anti-IL-6R therapy is currently the most common strategy in patients with ICI-induced inflammatory arthritis and insufficient response to glucocorticoids and methotrexate, leading to improvement in >80%. Overall, cancer progression occurred in about half of patients and whether the bDMARD/JAKi impacted the tumour response remains to be determined.

Efficacy and safety of rituximab in peripheral ulcerative keratitis associated with rheumatoid arthritis.

OBJECTIVE: Peripheral ulcerative keratitis (PUK) is a rare but severe ocular complication of rheumatoid arthritis (RA). It can be considered as an ocular manifestation of rheumatoid vasculitis (RV). Our case series aimed to evaluate the efficacy of rituximab (RTX) for PUK occurring in patients with RA. METHODS: Study population were patients with RA-associated PUK treated with RTX 1000 mg on days 1 and 15 at least once after the diagnosis. We identified patients referred to the rheumatology and ophthalmology departments of our hospital between February 2014 and June 2020. We also included patients referred by their specialist after being contacted through the Club Rhumatismes et Inflammation. Demographic data and clinical and biological features were retrospectively collected. RESULTS: We included seven patients (three men and four women, median age 58 years). All but one had a long-standing RA with a median disease duration of 13.9 years (IQR 0-30.2). RA was erosive in six out of seven patients. All patients had rheumatoid factors and anticitrullinated peptides antibodies were positive in six of them. PUK was complicated by corneal perforation in three patients and required surgery. After a median follow-up of 29.8 months (IQR 5-75), corneal inflammation was controlled in all patients. PUK recurred in one patient, 8 months after a single infusion of RTX. 71% of the patients presented a good articular response. No patient developed other manifestations of RV. No serious adverse event related to RTX was observed. CONCLUSION: RTX appears to be an efficient and safe therapeutic option in the treatment of RA-associated PUK.

Secukinumab and ustekinumab treatment in psoriatic arthritis: results of a direct comparison.

OBJECTIVES: To evaluate the characteristics of patients (pts) with PsA treated by ustekinumab (UST) or secukinumab (SEK) and to compare real-world persistence of UST and SEK in PsA. METHODS: In this retrospective, national, multicentre cohort study, pts with PsA (CASPAR criteria or diagnosis confirmed by the rheumatologist) initiating UST or SEK with a follow-up ≥6 months were included from January 2011 to April 2019. The persistence between SEK and UST was assessed after considering the potential confounding factors by using pre-specified propensity-score methods. Causes of discontinuation and tolerance were also collected. RESULTS: A total of 406 pts were included: 245 with UST and 161 with SEK. The persistence rate was lower in the UST group compared with the SEK group [median persistence 9.4 vs 14.7 months; 26.4% vs 38.0% at 2 years; weighted hazard ratio (HR) = 1.42; 95% CI: 1.07, 1.92; P =0.015]. In subgroup analysis, the persistence rate of SEK associated with MTX was significantly higher than that of UST associated with MTX: HR = 2.20; 95% CI: 1.30, 3.51; P =0.001, in contrast to SEK vs UST monotherapy: HR = 1.06; 95% CI: 0.74, 1.53; P =0.75. Discontinuation due to inefficacy was reported in 91.7% (SEK) and 82.4% (UST) of pts. Discontinuation due to an adverse event was reported in 12.2% (SEK) and 7.7% (UST) of pts. CONCLUSION: In this first study comparing UST and SEK, the persistence of SEK was higher than that of UST in PsA. In subgroup analysis, this difference was only found in association with MTX.

Bone and joint complications in patients with hereditary hemochromatosis: a cross-sectional study of 93 patients.

BACKGROUND: The aim of this study was to determine the frequency and characteristics of bone and joint complications, specifically bone fragility, joint replacement surgery, and arthropathy, in hereditary hemochromatosis (HH) and related factors. METHODS: This study was a cross-sectional observational study of 93 patients with HH. Radiographs of the hands, wrists, knees, and ankles were scored for joint space narrowing, erosions and cysts, osteophytes, and chondrocalcinosis. Prevalent (vertebral and non-vertebral) fragility fractures were recorded and bone mineral density (BMD) was systematically evaluated by dual energy X-ray absorptiometry. Bone fragility was defined as (i) a T-score ⩽ -2.5 at any site with or without a prevalent fragility fracture, or (ii) a T-score between -1.0 and -2.5 at any site and a prevalent fragility fracture. RESULTS: The mean age of the patients was 60.0 (11.2) years, and 58.0% of them were men. The frequency of radiographic MCP2-3 arthropathy was 37.6% (95% CI 0.28-0.48). Radiographic MCP2-3 arthropathy was independently associated with older age [OR 1.17 (1.09-1.26) per year, p < 0.0001], male sex [OR 3.89 (1.17-12.97), p = 0.027] and C282Y+/+ genotype [OR 4.78 (1.46-15.68), p = 0.010]. The frequency of joint replacement surgery was 12.9% (95% CI 0.07-0.21). The frequency of bone fragility was 20.4% (95% CI 0.13-0.30). Bone fragility was independently associated with hepatic cirrhosis [OR 8.20 (1.74-38.68), p = 0.008]. DISCUSSION: Radiographic MCP2-3 arthropathy was found to occur in 37.6% of patients with HH. The association observed between this form of arthropathy and C282Y homozygosity, male sex, and older age suggests that demographic characteristics and genetic background are likely to be major determinants of this joint disorder and play a more important role than severity of iron overload. Bone fragility was observed in a fifth of the patients with HH, independently of genetic background and severity of iron overload, and was strongly associated with hepatic cirrhosis. CONCLUSION: Future investigations should focus on pathogenesis and early identification of patients at risk of developing bone and joint complications secondary to HH.

Back pain following instillations of BCG for superficial bladder cancer is not a reactive complication: review of 30 Mycobacterium bovis BCG vertebral osteomyelitis cases.

Mycobacterium bovis Bacillus Calmette-Guérin (BCG) instillations are used in bladder cancer treatment. Adverse effects can occur. Osteoarticular complications are mainly reactive arthritis, but true infections have been described, such as vertebral osteomyelitis. We made a review of M. bovis BCG vertebral osteomyelitis after instillations for bladder cancer using PubMed search. We added three new French cases. Twenty-seven cases of BCG vertebral osteomyelitis had been reported on PubMed. Of the 30 cases, all were male, averaging 73.4 ± 8.7 years old. Median time between diagnosis and first and last instillation was 22.5 and 14 months respectively. Half of vertebral osteomyelitis was thoracic and lumbar in the other half. Sensitivo-motor deficit was present at diagnosis in 42% of cases. Other infectious locations were common, mainly infectious abdominal aortic aneurysms (20%). Rifampicin, ethambutol and isoniazid were the usual therapy. Poor outcomes were reported with 50% of one or more spine surgery. M. bovis BCG vertebral osteomyelitis following bladder instillation for bladder cancer is a rare complication. However, the late onset of back pain after instillations differentiates them from reactive arthritis. Concomitant septic location such as infectious abdominal aortic aneurysms must be known.