Immune checkpoint inhibitor-induced joint involvement.

Mending Broken Hearts

Apremilast for immune checkpoint inhibitor-induced psoriasis: A case series

Immune-Related Adverse Events and Outcomes in Patients with Advanced Non–Small Cell Lung Cancer: A Predictive Marker of Efficacy?

CA: A Cancer Journal for Clinicians publishes information about the prevention, early detection, and treatment of cancer, as well as nutrition, palliative care, survivorship, and additional topics of interest related to cancer care.

Mortality and immune-related adverse events after immune checkpoint inhibitor initiation for cancer among patients with pre-existing rheumatoid arthritis: a retrospective, comparative, cohort study.

BACKGOUND: The prevalence of rheumatoid arthritis (RA) and its specific autoantibodies varies in different populations. This variability depends on the genetic polymorphism of the immune response genes among which the HLA system plays a major role. AIM: We conducted a preliminary study of the distribution of HLA-DRB1 and HLA-DQB1 first field level alleles in a sample of 100 Albanian patients with RA. METHODS: In this context, we studied the HLA-DRB1 and HLA-DQB1 first-level allele frequencies in 100 Albanian patients with RA and considering their rheumatoid factor (RF) and anti-citrullinated peptide antibodies (ACPA) serologic subgroups. We compared them with the respective frequencies in a population of 191 Albanian individuals without known pathology. RESULTS: No differences were found between the controls and the RA patient group, but three statistically significant differences were found: an increase in DRB1*04 among ACPA-positive, RF-positive and ACPA-positive/RF-positive patients, a significant decrease in DRB1*11 among ACPA-positive/RF-positive, and also a decrease in DRB1*13 among RF-positive patient subgroups. The frequencies of DRB1 allotypes in ACPA+ and RF+ patients compared to their counterpart ACPA− and RF−patient subgroups showed the predisposing effect of HLA-DRB1*04 for ACPA and RF seropositivity (p, respectively, 0.0008 and 0.0017) and the protective role of HLA-DRB1*11 for ACPA and RF positivity (p, respectively, 0.007 and 0.02). The same protective role from the RF positivity is also found with the HLA-DRB1*13 alleles (p = 0.007). As far as the DQB1 locus is concerned, a protective association has been found between the HLA-DQB1*06 alleles with both RF+ and RF+ ACPA+ positivity (p, respectively, 0.05 and 0.04) when comparing the control group with the respective RA patient subgroups. In ACPA+ and RF+ patients compared to the ACPA− and RF− patient subgroups, the only detected difference was between RF (+) and RF (−) patients (p =0.04). CONCLUSION: The relatively low frequencies of DRB1*04 and high (DRB1*11 and DRB1*13) in the Albanian population might explain the rather low positivity rate of ACPA and RF antibodies among the Albanian RA patients. Our study demonstrates that DRB1*11, DRB1*13 and DQB1*06 may be negatively associated with RA. Conversely, DRB1*04 may confer susceptibility to RA in Albanian population.

<h3>Background</h3> Immune-related adverse events (irAEs) induced by immune checkpoint inhibitor (ICI) therapy can involve multiple organ systems, of which cutaneous irAEs (c-irAEs) are the most common.^1–5 Understanding co-occurrence patterns and...

Liver toxicity as a limiting factor to the increasing use of immune checkpoint inhibitors.

Background Immune checkpoint inhibitors (ICI) against CTLA-4 or PD-1/PD-L1 improve the survival of patients with advanced malignancies including melanoma, lung cancer among other tumours. Because of its mechanism of action, ICI are prone to produce different immune-related adverse events (irAEs), including musculo-skeletal manifestations. Objectives Our aim was to describe the experience with rheumatic irAEs in two tertiary centres. Methods All adult patients referred to the Rheumatology department from 2015 to 2018 because of the onset of musculo-skeletal symptoms following treatment with an ICI were included. Data collected comprised demographic features as well as ICI indication and type, history of rheumatic disease, disease manifestations at irAE onset, laboratory tests, ultrasound findings and treatment. Diagnostic and treatment approach was done according clinical judgment and in a daily clinical practice setting. Results 20 patients were included, 50% female, with a mean age of 61,5 years (range 32-83). The indication for ICI was melanoma in 10 cases, lung cancer in 5, urothelial neoplasia in 2 and squamous skin, breast and head and neck cancer in 1 case each. Pembrolizumab was the most used ICI accounting for 9 cases (1 combined with epacadostat), 8 patients were treated with Nivolumab (4 combined with Ipilimumab), 2 wit Atezolizumab (1 combined with Ibatasertib) and 1 Ipilimumab in monotherapy. A history of previous rheumatic disease was reported in 8 patients (1 seropositive RA, 1 Spondyloarthritis, 1 SLE, 1 gout, 1 chondrocalcinosis, 1 fibromyalgia, 1 De Quervain tendinitis, 1 hand osteoarthritis) and 1 had psoriasis. The most frequent irAE presentation was arthritis with 8 cases (40%), arthralgia in 4 cases (20%), 1 case of myalgia, 2 presented PMR-like symptoms, 1 tenosynovitis and 2 paraesthesia (1 with associated dysesthesia). After assessment, 7 patients were diagnosed as undifferentiated arthritis, 1 leukocytoclastic vasculitis, 1 small-vessel vasculitis, 2 psoriatic-like arthritis, 1 tenosynovitis, 2 PMR and 6 were classified as having non-inflammatory symptoms. Antibody status was analyzed in 16 patients. Anticitrullinated-peptide antibodies, rheumatoid factor and HLA B27 were negative in all cases (except for 1 patient with seropositive RA), ANAs were positive in 4 (including 1 patient with previous SLE) but without any specificities (i.e. ENAs) and ANCA were negative in one case with small-vessel vasculitis. Ultrasound assessment was performed in 6 patients, 3 presented synovial hypertrophy with positive power Doppler (1 with tenosynovitis associated), 1 peritendinous fluid collection, 1 elbow joint effusion and 1 bilateral supraspinatus calcified tendinopathy. Most patients were treated with glucocorticoids 12 (60%) and NSAID 6 (30%) and only 3 patients had to discontinue ICI treatment due to irAEs. Conclusion Our results were in line with previous studies showing that musculo-skeletal irAEs associated to ICI may present as a flare of a previous known rheumatic disease or as a de novo symptom. Most patients presented with asymmetric mono or oligoarthritis having a good response to GC and NSAID without the need of adding DMARD or withdraw of ICI therapy.. Disclosure of Interests Sebastian C Rodriguez-Garcia: None declared, DAVID LOBO: None declared, Raul Castellanos-Moreira Speakers bureau: MSD, Lilly, Ana Milena Millan Arciniegas: None declared, Roberto Gumucio: None declared, Ana Laiz Consultant for: Lilly, Novartis, AbbVvie, MSD, UCB and Janssen, Speakers bureau: Lilly, Novartis, Abvvie, MSD, UCB and Janssen, Virginia Ruiz-Esquide Speakers bureau: Sanofi, Lilly, MSD, Berta Magallares: None declared, Cesar Diaz-Torne: None declared, Patricia Moya: None declared, Ivan Castellvi Consultant for: I received fees less than 5000USD as a consultant for Kern and Actelion, Paid instructor for: I received fees less than 2000USD as a instructor for Boehringer -Ingelheim, Novartis and Gebro, Speakers bureau: ND, Hector Corominas: None declared, Jose A. Gomez-Puerta Consultant for: Pfizer, Roche, Speakers bureau: Abbvie, BMS, Janssen, MSD, Pfizer, Roche

Immunologic rheumatic disorders

Rationale:Immune checkpoint inhibitors (ICIs) have shown efficacy for the treatment of various kinds of malignant tumors. However, ICIs can cause immune-related adverse events, such as arthritis. Nevertheless, the treatment of ICI-induced arthritis has not been established yet. Here we report a case of ICI-induced polyarthritis successfully treated using sarilumab and monitored using joint ultrasonography.Patient concerns:A 61-year-old man presented with polyarthritis. He had been treated with nivolumab for recurrent renal cell carcinoma 11 months before. He developed ICI-induced nephritis (proteinuria and elevated serum creatinine) 3 months before, which resolved after discontinuing nivolumab for 1 month. Two months after resuming nivolumab, he developed polyarthralgia and joint swelling, which were suspected to be associated with nivolumab administration, and hence we discontinued nivolumab again. Laboratory tests revealed elevated C-reactive protein level and erythrocyte sedimentation rate, but were negative for rheumatoid factor and anti-cyclic citrullinated peptide antibody. Joint ultrasonography revealed active synovitis in several joints, but a joint X-ray revealed no bone erosion.Diagnoses:We diagnosed polyarthritis as ICI-induced arthritis because the findings were not typical of rheumatoid arthritis (no bone erosion and seronegativity) and the patient had already developed other immune-related adverse events (ICI-induced nephritis).Interventions:After discontinuation of nivolumab, we started treatment with 15 mg daily prednisolone and 1000 mg daily sulfasalazine, although it was ineffective. Hence, we initiated 200 mg biweekly sarilumab.Outcomes:Following sarilumab administration, polyarthritis improved rapidly, and joint ultrasonography confirmed the rapid improvement of synovitis. Hence, we tapered off the glucocorticoid treatment. No recurrence of renal cell carcinoma was noted for 2 years after the initiation of sarilumab despite no anti-tumor therapy.Lessons:Sarilumab may serve as a good treatment option for treating refractory ICI-induced polyarthritis. Joint ultrasonography may contribute to the evaluation of ICI-induced polyarthritis and monitoring the effects of treatments.

Incidence and Predictors of CKD and Estimated GFR Decline in Patients Receiving Immune Checkpoint Inhibitors

Objectives To investigate the potential association between tumour necrosis factor (TNF) inhibitor treatment and malignant melanomas in rheumatoid arthritis, melanoma risks in rheumatoid arthritis patients not treated with biological drugs,...

FRI0136 Risk for Lung Cancer in RA and Different RA Phenotypes: Results from A Population-Based Case-Control Study

Immune checkpoint inhibitors (ICIs) have improved survival in patients with advanced melanoma but can be associated with a spectrum of immune-related adverse events (AEs), including both autoimmune-related AEs and other immune-related inflammatory AEs. These associations have primarily been evaluated in clinical trials that include highly selected patients, with older adults often underrepresented. To evaluate the association between use of ICIs and immune-related AEs (autoimmune and other immune related) among older patients with cutaneous melanoma. A population-based cohort study was conducted from January 1, 2011, to December 31, 2015. Data were analyzed from January 31 to May 31, 2021. With use of a linked database of Medicare claims and Surveillance, Epidemiology, and End Results (SEER) Program population-based cancer registries, patients of White race diagnosed with stages II-IV or unknown (American Joint Committee on Cancer, AJCC Cancer Staging Manual 6th edition) first primary cutaneous melanoma during 2011-2015, as reported to SEER, and followed up through December 31, 2015, were identified. Immune checkpoint inhibitors for treatment of melanoma. The association between ICIs and immune-related AEs ascertained from Medicare claims data was estimated using multivariable Cox regression with hazard ratios (HRs) and 95% CIs and with cumulative incidence accounting for competing risk of death. The study included 4489 patients of White race with first primary melanoma (3002 men [66.9%]; median age, 74.9 [range, 66.0-84.9] years). During follow-up (median, 1.4 [range, 0-5.0] years), 1576 patients (35.1%) had an immune-related AE on a Medicare claim. Use of ICIs (reported for 418 patients) was associated with autoimmune-related AEs (HR, 2.5; 95% CI, 1.6-4.0), including primary adrenal insufficiency (HR, 9.9; 95% CI, 4.5-21.5) and ulcerative colitis (HR, 8.6; 95% CI, 2.8-26.3). Immune checkpoint inhibitors also were associated with other immune-related AEs (HR, 2.2; 95% CI, 1.7-2.8), including Cushing syndrome (HR, 11.8; 95% CI, 1.4-97.2), hyperthyroidism (HR, 6.3; 95% CI, 2.0-19.5), hypothyroidism (HR, 3.8; 95% CI, 2.4-6.1), hypopituitarism (HR, 19.8; 95% CI, 5.4-72.9), other pituitary gland disorders (HR, 6.0; 95% CI, 1.2-30.2), diarrhea (HR, 3.5; 95% CI, 2.5-4.9), and sepsis or septicemia (HR, 2.2; 95% CI, 1.4-3.3). Most associations were pronounced within 6 months following the first ICI claim and comparable with or without a baseline history of autoimmune disease. The cumulative incidence at 6 months following the first ICI claim was 13.7% (95% CI, 9.7%-18.3%) for autoimmune-related AEs and 46.8% (95% CI, 40.7%-52.7%) for other immune-related AEs. In this cohort study of older adults with melanoma, ICIs were associated with autoimmune-related AEs and other immune-related AEs. Although some findings were consistent with clinical trials of ICIs, others warrant further investigation. As ICI use continues to expand rapidly, ongoing investigation of the spectrum of immune-related AEs may optimize management of disease in patients.