DPP4 inhibitor-induced polyarthritis: a report of three cases

Crickx, Étienne; Marroun, Ibrahim; Veyrie, C.; Beller, Christine Le; Schoindre, Y.; Bouilloud, F.; Blëtry, O.; Kahn, Jean‐Emmanuel

doi:10.1007/s00296-013-2710-7

Cited by 47 publications

(28 citation statements)

References 8 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The involvement of CD26/DPP4 in arthritis has been reviewed recently, involving glycosylation and DPP4 autoantibodies on one hand and SDF‐α on the other hand . Additionally, one study summarizes three cases of DPP4 inhibitor‐induced polyarthritis .…”

Section: Involvement Of Cd26/dpp4 In Pathologymentioning

confidence: 98%

Cut to the chase: a review of CD26/dipeptidyl peptidase-4's (DPP4) entanglement in the immune system

Klemann

Wagner

Stephan

et al. 2016

Clinical and Experimental Immunology

362

437

View full text Add to dashboard Cite

SummaryCD26/DPP4 (dipeptidyl peptidase 4/DP4/DPPIV) is a surface T cell activation antigen and has been shown to have DPP4 enzymatic activity, cleaving-off amino-terminal dipeptides with either L-proline or L-alanine at the penultimate position. It plays a major role in glucose metabolism by Nterminal truncation and inactivation of the incretins glucagon-like peptide-1 (GLP) and gastric inhibitory protein (GIP). In 2006, DPP4 inhibitors have been introduced to clinics and have been demonstrated to efficiently enhance the endogenous insulin secretion via prolongation of the half-life of GLP-1 and GIP in patients. However, a large number of studies demonstrate clearly that CD26/DPP4 also plays an integral role in the immune system, particularly in T cell activation. Therefore, inhibition of DPP4 might represent a double-edged sword. Apart from the metabolic benefit, the associated immunological effects of long term DPP4 inhibition on regulatory processes such as T cell homeostasis, maturation and activation are not understood fully at this stage. The current data point to an important role for CD26/DPP4 in maintaining lymphocyte composition and function, T cell activation and co-stimulation, memory T cell generation and thymic emigration patterns during immune-senescence. In rodents, critical immune changes occur at baseline levels as well as after in-vitro and in-vivo challenge. In patients receiving DPP4 inhibitors, evidence of immunological side effects also became apparent. The scope of this review is to recapitulate the role of CD26/DPP4 in the immune system regarding its pharmacological inhibition and T cell-dependent immune regulation.Keywords: autoimmunity, B cell, cell activation, chemokines, T cells Structure and characterization of CD26Originally described 50 years ago [1], the lymphocyte cell surface protein CD26 possess a dipeptidyl peptidase-4 (DPP4) activity. It cleaves dipeptides from the N-termini of oligopeptides and smaller peptides with proline or alanine at the penultimate position, as illustrated in Fig. 1b [International Union of Biochemistry and Molecular Biology (IUBMB) Enzyme Nomenclature EC 3.4.14.5].CD26/DPP4 is a homodimer and an integral type II glycoprotein anchored to the membrane by its signal peptide. The primary structure consists of a short six amino acid cytoplasmic tail, a 22 amino acid transmembrane, a 738 amino acid extracellular portion comprised of a flexible stalk, glycosylation-rich region, cysteine-rich region and catalytic region with the catalytic triad Ser 630 , Asp 708 and His 740 (Fig. 1e). Recent studies have revealed that the transmembrane region contributes to enzyme activity and quaternary structure by dimerization [2]. The crystal structure of human CD26/DPP4 has been elucidated to reveal two domains: an eight-bladed propeller and an a/b-hydrolase domain. The propeller is open and consists of two subdomains made up of blades II-V and VI-VIII for the glycosylation-rich and cysteine-rich regions, respectively (Fig. 1d). Most monoclonal anti-CD26/DPP4 antibodies,...

show abstract

Section: Involvement Of Cd26/dpp4 In Pathologymentioning

confidence: 98%

Cut to the chase: a review of CD26/dipeptidyl peptidase-4's (DPP4) entanglement in the immune system

Klemann

Wagner

Stephan

et al. 2016

Clinical and Experimental Immunology

362

437

View full text Add to dashboard Cite

show abstract

“…However, when data from these large trial was pooled, there was a significantly increased risk for pancreatitis in the DPP‐4 inhibitor treated patients (OR 1.79; 95% CI 1.13‐2.82, P = .013), yet the absolute risk increase was small (0.13%) . Dipeptidyl peptidase‐4 inhibitors have also been associated with polyarthritis, which seems to be reversible upon discontinuation of therapy …”

Section: Safetymentioning

confidence: 99%

“…95% CI 1.13-2.82, P = .013), yet the absolute risk increase was small (0.13%). 96 Dipeptidyl peptidase-4 inhibitors have also been associated with polyarthritis, 97,98 which seems to be reversible upon discontinuation of therapy. 98 In May 2016, the US Food and Drug Administration issued an alert about the possibility of an increased risk of amputations with canagliflozin arising from an interim analysis of the CANVAS trial.…”

Section: Other Possible Safety Concernsmentioning

confidence: 99%

When metformin is not enough: Pros and cons of SGLT2 and DPP‐4 inhibitors as a second line therapy

Avogaro

Delgado

Lingvay

2018

Diabetes Metabolism Res

View full text Add to dashboard Cite

The newer oral therapies for type 2 diabetes mellitus, dipeptidyl peptidase-4 (DPP-4) inhibitors and sodium glucose cotransporter 2 (SGLT2) inhibitors, have advantages over older agents. Dipeptidyl peptidase-4 inhibitors are weight neutral and have few adverse effects. Sodium glucose cotransporter 2 inhibitors have additional benefits: weight loss, blood pressure reduction, cardiovascular risk reduction, and renoprotective effects. Sodium glucose cotransporter 2 inhibitors have increased risk of urogenital infections and possible risk of "euglycaemic" diabetic ketoacidosis. It is important to balance the benefits over the older-oral therapies as these agents are more expensive; yet some analyses suggest that they are within the limits of what is considered cost-effective in health care. We discuss the relative merits and drawbacks of these 2 classes and consider their roles in the treatment of type 2 diabetes mellitus. We suggest a number of patient profiles where early use of these agents could be used. We favour the use of SGLT2 inhibitors over DPP-4 inhibitors as add on therapy to metformin when glycaemic targets have not been achieved given their similar glycaemic efficacy and the additional benefits of SGLT2 inhibitors. We particularly favour SGLT2 inhibitors in those where additional weight loss and blood pressure reductions are desired, and in patients with heart failure or cardiovascular disease. Care should be taken to warn patients about genital fungal infections and to avoid use in people with risk factors for SGLT2 associated ketoacidosis. We favour DPP-4 inhibitors in those where side effects of other agents are of concern, the frail elderly population, and those with renal disease precluding SGTL2 inhibitor use.

show abstract

“…20 While studies suggested a potential role of DPP4i as a novel therapy for several inflammatory diseases by inhibiting T cell proliferation and cytokine production, 6 7 21-27 a few cases of inflammatory arthritis potentially related to use of DPP4i have been reported. 28 The objective of this study was to estimate the risk of incident systemic AD including RA, systemic lupus erythematosus, psoriasis, psoriatic arthritis, multiple sclerosis and inflammatory bowel disease in patients with diabetes starting a DPP4i drug compared with those starting non-DPP4i oral hypoglycaemic agents. We hypothesised that patients starting a DPP4i would have a reduced risk of incident RA and other AD compared with those starting non-DPP4i drugs only.…”

Section: Introductionmentioning

confidence: 99%

Dipeptidyl peptidase-4 inhibitors in type 2 diabetes may reduce the risk of autoimmune diseases: a population-based cohort study

et al. 2014

View full text Add to dashboard Cite

Objective Dipeptidyl peptidase-4 (DPP4), also known as CD26, is a transmembrane glycoprotein which has a co-stimulatory function in the immune response. DPP4 inhibitors (DPP4i) are oral glucose-lowering drugs for type 2 diabetes mellitus (T2DM). This study evaluated the risk of incident rheumatoid arthritis (RA) and other autoimmune diseases (AD) such as systemic lupus erythematosus, psoriasis, multiple sclerosis, and inflammatory bowel disease, associated with DPP4i in patients with T2DM. Methods Using U.S. insurance claims data (2005–2012), we conducted a population-based cohort study that included initiators of combination therapy with DPP4i (DPP4i plus metformin) and non-DPP4i (non-DPP4i plus metformin). RA and other AD were identified with ≥2 diagnoses and ≥1 dispensing for AD-specific immunomodulating drugs or steroids. Composite AD includes RA or other AD. Propensity score (PS)-stratified Cox proportional hazards models compared the risk of AD in DPP4i initiators vs. non-DPP4i, controlling for potential confounders. Results After asymmetric trimming on the PS, 73,928 patients with T2DM starting DPP4i combination therapy and 163,062 starting non-DPP4i combination therapy were selected. Risks of incident RA and composite AD were lower in the DPP4i group vs. non-DPP4i with the PS-stratified hazard ratio of 0.66 (95% CI 0.44–0.99) for RA, 0.73 (0.51–1.03) for other AD, and 0.68 (95% CI 0.52–0.89) for composite AD. Conclusions In this large cohort of diabetic patients, those initiating DPP4i combination therapy appear to have a decreased risk of incident AD including RA compared to those initiating non-DPP4i combination therapy. These results may suggest possible pharmacologic pathways for prevention or treatment of AD.

show abstract

DPP4 inhibitor-induced polyarthritis: a report of three cases

Cited by 47 publications

References 8 publications

Cut to the chase: a review of CD26/dipeptidyl peptidase-4's (DPP4) entanglement in the immune system

Cut to the chase: a review of CD26/dipeptidyl peptidase-4's (DPP4) entanglement in the immune system

When metformin is not enough: Pros and cons of SGLT2 and DPP‐4 inhibitors as a second line therapy

Dipeptidyl peptidase-4 inhibitors in type 2 diabetes may reduce the risk of autoimmune diseases: a population-based cohort study

Contact Info

Product

Resources

About