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Correspondence on 'Immune checkpoint inhibitor-induced inflammatory arthritis persists after immunotherapy cessation’ by Braaten et al
  1. Fulvia Ceccarelli1,
  2. Andrea Botticelli2,
  3. Alain Jonathan Gelibter2,
  4. Ilaria Leccese1,
  5. Ramona Lucchetti1,
  6. Enrico Cortesi2,
  7. Guido Valesini1,
  8. Paolo Marchetti2,
  9. Fabrizio Conti1
  1. 1 Arthritis Center, Dipartimento di Scienze Cliniche Internistiche, Anestesiologiche e Cardiovascolari, Sapienza Università di Roma, Sapienza University of Rome, Roma, Italy
  2. 2 Oncologia, Dipartimento di Medicina Clinica e Molecolare, Sapienza University of Rome, Roma, Italy
  1. Correspondence to Dr Fulvia Ceccarelli, Arthritis Center, Dipartimento di Scienze Cliniche Internistiche, Anestesiologiche e Cardiovascolari, Sapienza Università di Roma, Sapienza University of Rome, Roma 00161, Italy; fulviaceccarelli{at}

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We read with interest the study published by Braaten and colleagues, analysing the long-term outcomes of 60 patients developing persistent inflammatory arthritis (IA) after immune checkpoint inhibitors (ICIs) cessation. The most relevant result of the study was the presence of active arthritis in more than half of the patients at the last follow-up visit.1

We report here our experience in the context of a joint oncology/rheumatology outpatient clinic, in order to evaluate the risk of developing IA in patients treated by anti-PD1 drugs. During 1-year period, we consecutively assessed all the adult patients candidate to anti-PD1 treatment, referring to the Oncology Unit at the Sapienza University of Rome. After treatment starts, in the case of musculoskeletal manifestations, patients were referred to the Sapienza Arthritis Center, Rheumatology Unit, Sapienza University of Rome. Arthritis was defined as the occurrence of at least one episode of clinical synovitis, with morning stiffness lasting at least 30 min. IA activity was assessed by disease activity score on 28 joints by ESR (DAS28-ESR).2 We investigated the presence of rheumatoid factor (RF), anticitrullinated protein (ACPA) and antinuclear antibodies. In the clinically involved joints, ultrasonographic assessment was performed according to EULAR guidelines.3

We evaluated 72 patients (M/F 48/24, median age 66 years, IQR 13.0) affected by lung cancer (75.1%), renal cancer (15.3%), melanoma skin cancer (6.9%), or other neoplastic diseases (2.7%). Sixty-seven patients were treated with nivolumab and the remaining with pembrolizumab (median treatment duration 7 months, IQR 13.0). After 3 months of follow-up, the malignant disease had not progressed in 48 patients (66.7%), whereas an exitus was registered in 21 patients (29.2%). During the follow-up period, seven Caucasian patients (9.7%) developed clinically evident synovitis (absolute risk for IA 0.1, incidence rate 0.01). Table 1 reports the main demographic, oncologic and rheumatological features of these patients. Two patients could be classified as affected by rheumatoid arthritis (RA) according to ACR/EULAR 2010 criteria,4 seropositive in one case (RF and ACPA). Autoantibodies assessment was negative in the remaining patients. Five patients (71.4%) were treated with prednisone (starting dosage 10–12.5 mg/daily, with 2.5 mg reduction every 2 weeks until drug stopping) and the remaining two with non-steroidal anti-inflammatory drugs (NSAIDs) (diclofenac 150 mg/daily for 15 consecutive days). The above-mentioned treatments induced a quick, complete and persistent response in all the patients, except for the seropositive RA subject, in which subcutaneous methotrexate (10 mg/weekly) was added after 4 weeks, achieving a remission status in 3 months. All the patients continued ICIs treatment.

Table 1

Demographic features, malignancy history, rheumatological, clinical and ultrasonographic manifestations, time to onset, autoantibody profile and treatment of the seven patients developing synovitis. Active synovitis was defined by the presence of power Doppler signal.

Several differences could be identified by comparing our cohort with the one described by Braaten and colleagues. The previous study included patients developing IA after ICIs cessation, whereas in our cohort, IA appeared during treatment. Nonetheless, in the majority of our patients with IA, treatment with glucocorticoids or NSAIDs was able to induce a prompt and persistent remission. The only patient requiring a disease-modifying anti-rheumatic drug (DMARD) was affected by seropositive RA. Conversely, more than half of the patients evaluated in the Braaten’s study showed an active disease at the last visit, as confirmed by the need to introduce synthetic and/or biological DMARDs. In our opinion, this is the most relevant difference between the two cohorts, and this could be explained by the different ICIs treatment. We selected patients treated by anti-PD1, in order to make the cohort homogeneous, whereas the other study included different ICIs. In conclusion, the high risk to develop IA in ICs inhibitors-treated patients confirms the need to include the rheumatologist in the management of these subjects, as recently underlined in the literature review conducted by Jamal and colleagues.5 The longitudinal assessment of these patients could allow the identification of subjects at risk to develop this specific adverse event.

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  • Contributors FCe, AB, PM and FC make substantial contributions to the conception or design of the work, the acquisition, analysis and interpretation of data, to draft the work and revising it critically for important intellectual content. AG, IL, RL contributed to data acquisition and interpretation and to draft paper. GV make substantial contributions to the conception or design of the work and revising it critically for important intellectual content. All the authors provided a final approval of the version published.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; internally peer reviewed.

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