Identification of outcome domains in immune checkpoint inhibitor-induced inflammatory arthritis and polymyalgia rheumatica: A scoping review by the OMERACT irAE working group

Ghosh, Nina; Couette, Nina; Binsbergen, Wouter H. van; Weinmann, Sophia C; Jivanelli, Bridget; Shea, Beverley; Bass, Anne R.; Benesova, Karolina; Bingham, Clifton O.; Calabrese, Cassandra; Cappelli, Laura C.; Chan, Karmela Kim; Choy, Ernest; Daoussis, Dimitrios; Goodman, Susan M.; Hudson, Marie; Jamal, Shahin; Leipe, Jan; López-Olivo, María A.; Suarez‐Almazor, María E.; Laken, Conny J. van der; Liew, David; Kostine, Marie

doi:10.1016/j.semarthrit.2022.152110

Cited by 13 publications

(6 citation statements)

References 21 publications

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“…1 2 6-11 A strength of our study is the comprehensive prospective collection of data (169 parameters) on R-irAE and cancer with extensive statistical analysis limited to two cancer subgroups and reporting depth rarely found in other studies according to a recent scoping literature review. 5 Limitations of this study include shared decisionmaking as an important factor in DMARD initiation and limited statistical power for some outcomes due to small numbers of patients for certain subgroups. Furthermore, we chose to focus here specifically on R-irAEs in routine interdisciplinary care without comparison to non-(R-) irAE controls, nor the exploration of novel molecular biomarkers, as we have addressed both in previous studies.…”

Section: Discussionmentioning

confidence: 98%

“… 1 5 Valid data from prospective studies as well as classification and outcome measures are largely missing for R-irAEs. 5 However, they cannot be derived from previous large ICI clinical trials due to under-recognition/under-reporting of R-irAEs and shortcomings of the Common Terminology Criteria for Adverse Events for R-irAEs. 1 2 6–11 This also leaves unanswered the question of whether R-irAE characteristics differ according to the underlying tumor as described for skin and gastrointestinal irAEs.…”

Section: Introductionmentioning

confidence: 99%

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Sex and anti-inflammatory treatment affect outcome of melanoma and non-small cell lung cancer patients with rheumatic immune-related adverse events

Gente,

Diekmann,

Daniello

et al. 2023

J Immunother Cancer

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BackgroundRheumatic immune-related adverse events (R-irAEs) occur in 5–15% of patients receiving immune checkpoint inhibitors (ICI) and, unlike other irAEs, tend to be chronic. Herein, we investigate the factors influencing cancer and R-irAEs outcomes with particular focus on adverse effects of anti-inflammatory treatment.MethodsIn this prospective, multicenter, long-term, observational study, R-irAEs were comprehensively analyzed in patients with malignant melanoma (MM, n=50) and non-small cell lung cancer (NSCLC, n=41) receiving ICI therapy who were enrolled in the study between August 1, 2018, and December 11, 2022.ResultsAfter a median follow-up of 33 months, progressive disease or death occurred in 66.0% and 30.0% of MM and 63.4% and 39.0% of patients with NSCLC. Male sex (progression-free survival (PFS): p=0.013, and overall survival (OS): p=0.009), flare of a pre-existing condition (vs de novo R-irAE, PFS: p=0.010) and in trend maximum glucocorticoid (GC) doses >10 mg and particularly ≥1 mg/kg prednisolone equivalent (sex-adjusted PFS: p=0.056, OS: p=0.051) were associated with worse cancer outcomes. Patients receiving disease-modifying antirheumatic drugs (DMARDs) showed significantly longer PFS (n=14, p=0.011) and OS (n=20, p=0.018). Effects of these variables on PFS and/or OS persisted in adjusted Cox regression models. Additionally, GC treatment negatively correlated with the time from diagnosis of malignancy and the latency from ICI start until R-irAE onset (all p<0.05). R-irAE features and outcomes were independent of other baseline patient characteristics in both studied cancer entities.ConclusionMale sex, flare of pre-existing rheumatologic conditions and extensive GC treatment appeared to be linked with unfavorable cancer outcomes, while DMARD use had a favorable impact. These findings challenge the current dogma of restrictive DMARD use for R-irAE and thus may pave the way to better strategies and randomized controlled trials for the growing number of patients with R-irAE.

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Section: Discussionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

Sex and anti-inflammatory treatment affect outcome of melanoma and non-small cell lung cancer patients with rheumatic immune-related adverse events

Gente,

Diekmann,

Daniello

et al. 2023

J Immunother Cancer

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“…Secondly, drugs may interfere with the Immune tolerance mechanism, causing the immune system to attack normal joint tissues. Finally, arthralgia may also be due to the influence of drugs on the neural network, resulting in sensory abnormalities and changes in pain signal transmission ( 26 ). These indicates the use of immune checkpoint inhibitors may bring a series of adverse events.…”

Section: Discussionmentioning

confidence: 99%

Arthralgia adverse events due to immune-checkpoint inhibitors for lung cancer patients: a systematic review and meta-analysis

Zou,

Wang,

Sun

et al. 2023

Front. Oncol.

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BackgroundImmune agents targeting Programmed cell death-1 (PD-1) are a new type of cancer treatment drugs. By inhibiting the interaction between PD-1 and PD-L1, the ability of the immune system to attack tumor cells is enhanced. These immune preparations have shown significant efficacy in the treatment of various malignant tumors. However, like other drugs, immune preparations targeting PD-1 may also cause side effects, including arthralgia. Therefore, we conduct a meta-analysis to assess whether immune-checkpoint inhibitors targeting programmed cell death-1 in lung cancer patients will lead to arthralgia adverse events.MethodsWe conducted a comprehensive search across multiple databases, including PubMed, Medline (Ovid), Web of Science, Cochrane, Embase, Scopus, CKNI, Wang fang, VIP database, Sino Med, and Clinical Trails, to identify relevant studies. The search encompassed articles published up until June 20th, 2023. The primary outcome is adverse events about arthralgia and secondary outcomes are any other related with arthralgia. Data extraction was carried out by two independent individuals, and the Cochrane Risk of Bias tool version 2.0 was employed to assess the included studies. The systematic review and meta-analysis were conducted using RevMan 5.3 software.Results12 studies are included in the meta-analysis. All included studies were determined to have a low risk of random sequence generation bias. The meta-analysis result showed that arthralgia RR = 1.11, 95% CI [0.88, 1.40], I2 = 56%, back pain RR = 1.86, 95% CI [1.07, 3.26], I2 = 84%, myalgia RR = 0.49, 95% CI [0.27, 0.88], I2 = 86% and muscular pain RR = 1.97, 95% CI [1.40, 2.77], I2 = 23%.ConclusionThe use of targeted inhibitors may lead to an increased incidence of back pain, while potentially reducing the occurrence of myalgia. On the other hand, immune-checkpoint inhibitors targeting programmed cell death-1 in lung cancer patients may not cause arthralgia and muscular pain.

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“…PMR recently emerged as a side effect of cancer immunotherapy [ 148 , 149 , 150 , 151 , 152 , 153 , 154 ]. Compared with anti-CTLA-4 antibodies, anti-PD-1/PD-L1 antibodies have a higher risk of inducing this manifestation [ 103 ].…”

Section: Rheumatic Iraesmentioning

confidence: 99%

Rheumatic Immune-Related Adverse Events due to Immune Checkpoint Inhibitors—A 2023 Update

Dang¹,

Watanabe²,

Shiomi³

et al. 2023

IJMS

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With the aging of the population, malignancies are becoming common complications in patients with rheumatoid arthritis (RA), particularly in elderly patients. Such malignancies often interfere with RA treatment. Among several therapeutic agents, immune checkpoint inhibitors (ICIs) which antagonize immunological brakes on T lymphocytes have emerged as a promising treatment option for a variety of malignancies. In parallel, evidence has accumulated that ICIs are associated with numerous immune-related adverse events (irAEs), such as hypophysitis, myocarditis, pneumonitis, and colitis. Moreover, ICIs not only exacerbate pre-existing autoimmune diseases, but also cause de novo rheumatic disease–like symptoms, such as arthritis, myositis, and vasculitis, which are currently termed rheumatic irAEs. Rheumatic irAEs differ from classical rheumatic diseases in multiple aspects, and treatment should be individualized based on the severity. Close collaboration with oncologists is critical for preventing irreversible organ damage. This review summarizes the current evidence regarding the mechanisms and management of rheumatic irAEs with focus on arthritis, myositis, and vasculitis. Based on these findings, potential therapeutic strategies against rheumatic irAEs are discussed.

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Identification of outcome domains in immune checkpoint inhibitor-induced inflammatory arthritis and polymyalgia rheumatica: A scoping review by the OMERACT irAE working group

Cited by 13 publications

References 21 publications

Sex and anti-inflammatory treatment affect outcome of melanoma and non-small cell lung cancer patients with rheumatic immune-related adverse events

Sex and anti-inflammatory treatment affect outcome of melanoma and non-small cell lung cancer patients with rheumatic immune-related adverse events

Arthralgia adverse events due to immune-checkpoint inhibitors for lung cancer patients: a systematic review and meta-analysis

Rheumatic Immune-Related Adverse Events due to Immune Checkpoint Inhibitors—A 2023 Update

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