Pembrolizumab-induced psoriatic arthritis treated with disease-modifying anti-rheumatic drugs in a patient with gastric cancer:A case report

BACKGROUND Immune checkpoint inhibitor(ICI)-induced rheumatic immune-related adverse events(ir AEs)have been infrequently reported,and the treatment of severe or refractory arthritis as ir AEs has not been established yet.CASE SUMMARY The patient was a 67-year-old man with a history of well-controlled foot psoriasis who presented with polyarthralgia.He had received pembrolizumab for metastatic gastric adenocarcinoma 2 mo previously.Physical examination revealed erythematous swelling in the distal interphalangeal joints,left shoulder,and both knees.He had plaque psoriasis with psoriatic nail dystrophy and dactylitis in the distal joints of the fingers and toes.Inflammatory markers including C-reactive protein and erythrocyte sedimentation rate were elevated but rheumatoid factor and anticyclic citrullinated peptide antibody were negative.The patient was diagnosed with psoriatic arthritis(PsA)and started on methylprednisolone 1 mg/kg/day after pembrolizumab discontinuation.However,despite 1 wk of methylprednisolone treatment,PsA worsened;hence,leflunomide and methotrexate were started.After 4 wk of steroid treatment,PsA worsened and improved repeatedly with steroid tapering.Therefore,the therapy was intensified to include etanercept,a tumor necrosis factor inhibitor,which ultimately resulted in adequate PsA control.CONCLUSION This is the first report of ICI-induced PsA in a gastric cancer patient.Some rheumatic ir AEs with refractory severe arthritis may require disease-modifying anti-rheumatic drugs and long-term management.

Blood glucose changes surrounding initiation of tumor-necrosis factor inhibitors and conventional disease-modifying anti-rheumatic drugs in veterans with rheumatoid arthritis

AIM To determine the scope of acute hypoglycemic effects for certain anti-rheumatic medications in a large retrospective observational study. METHODS Patients enrolled in the Veterans Affairs Rheumatoid Arthritis (VARA) registry were selected who, during follow-up, initiated treatment with tumor necrosis factor inhibitors (TNFi's, including etanercept, adalimumab, infliximab, golimumab, or certolizumab), prednisone, or conventional disease-modifying anti-rheumatic drugs(DMARDs), and for whom proximate random blood glucose (RBG) measurements were available within a window 2-wk prior to, and 6 mo following, medication initiation. Similar data were obtained for patients with proximate values available for glycosylated hemoglobin A1C values within a window 2 mo preceding, and 12 mo following, medication initiation. RBG and A1C measurements were compared before and after initiation events using paired t-tests, and multivariate regression analysis was performed including established comorbidities and demographics.RESULTS Two thousands one hundred and eleven patients contributed at least one proximate measurement surrounding the initiation of any examined medication. A significant decrease in RBG was noted surrounding 653 individual hydroxychloroquine-initiation events(-3.68 mg/dL, P = 0.04), while an increase was noted for RBG surrounding 665 prednisone-initiation events(+5.85 mg/d L, P < 0.01). A statistically significant decrease in A1C was noted for sulfasalazine initiation, as measured by 49 individual initiation events(-0.70%, P < 0.01). Multivariate regression analyses, using methotrexate as the referent, suggest sulfasalazine (β =-0.58, P = 0.01) and hydroxychloroquine(β =-5.78, P = 0.01) use as predictors of lower post-medicationinitiation RBG and A1C values, respectively. Analysis by drug class suggested prednisone (or glucocorticoids) as predictive of higher medication-initiation event RBG among all start events as compared to DMARDs, while this analysis did not show any drug class-level effect for TNFi. A diagnosis of congestive heart failure(β = 4.69, P = 0.03) was predictive for higher post-initiation RBG values among all medication-initiation events.CONCLUSION No statistically significant hypoglycemic effects surrounding TNFi initiation were observed in this large cohort. Sulfasalazine and hydroxychloroquine may have epidemiologically significant acute hypoglycemic effects.

Study on Therapeutic Mechanism of Anti-Rheumatism Effect of Siegesbeckia Pubescens

Objective: To explore the mechanism of anti-rheumatic effect of the active fraction of Siegesbeckia pubescens (AFSP). Methods: Adjuvant arthritis (AA) model of rat was produced to observe the effect of AFSP on lymphocyte proliferation, interleukin-1 and -2 (IL-1,-2) activity, pathologic section of ankle joint, and analgesic effect, in model rat. Results: AFSP could reduce the inflammatory pathologic response of ankle joint. It has good analgesic effect, the analgesic rate being 65%. AFSP could also strengthen T-lymphocyte proliferation, promote IL-2 activity and inhibit IL-1 activity. Compared with the control group, the difference was significant (P<0.01). Conclusion: By means of regulating the immune function of organism, AFSP could improve the local pathologic response to antagonize against rheumatism, therefore, it is an effective anti-rheumatism herbal medicine.

Clinical deep remission and related factors in a large cohort of patients with rheumatoid arthritis

Background:Clinical remission is the treatment target in rheumatoid arthritis (RA).This study aimed to investigate clinical remission and related factors in a large cohort of patients with RA.Methods:This study composed of 342 patients with RA.Data were collected by face-to-face interview of 1049 patients with RA who visited the Department of Rheumatology of three teaching hospitals from September 2015 to May 2016.The patients with RA were clinically assessed by rheumatologists and a four-page questionnaire was completed on site.Subsequently,patients fulfilled remission criteria were further analyzed.The practicability of different definitions of remission of RA was rated by a panel of rheumatologists.Sustained intensive disease modifying anti-rheumatic drug (DMARD) treatment was defined as a combination treatment with two or more DMARDs for at least 6 months.Results:In this cohort of 342 patients with RA,the proportions of patients achieving remission were 38.0%,29.5%,24.9%,21.1%,19.0%,18.1%,and 17.0%,based on criteria of disease activity score in 28 joints (DAS28) using CRP (DAS28-CRP),DAS28 using ESR (DAS28-ESR),routine assessment of patient index data 3 (RAPID-3),Boolean,simplified disease activity index (SDAI),clinical disease activity index,and the newly described clinical deep remission (CliDR),respectively.Boolean and CliDR are the best in practicability scored by rheumatologists (7.5 and 8.0,respectively).Compared with the non-sustained intensive group,sustained intensive treatment with DMARDs yielded higher remission rates of 25.6%,23.8%,and 21.3% in patients with RA based on Boolean (χ^2=3.937,P=0.047),SDAI (χ^2=4.666,P=0.031),and CliDR criteria (χ^2=4.297,P=0.038).The most commonly prescribed conventional synthesized DMARDs (csDMARDs) in patients with RA was leflunomide,followed by methotrexate,and hydroxychloroquine.Compared with the non-remission group,patients achieving remission had a longer median duration of DMARDs (45.0 [22.8–72.3] months,Z=-2.295,P=0.022).Conclusions:The findings in this study indicated that clinical deep remission is achievable in patients with RA.Sustained intensive DMARD treatment is needed to achieve a better outcome in RA.

Coexisting ankylosing spondylitis and rheumatoid arthritis： A case report with literature review

A 30-year-old female patient with coexisting ankylosing spondylitis and rheumatoid arthritis was diagnosed and treated. The human leukocyte antigen （HLA）-B27 is a predisposing factor of ankylosing spondylitis and HLA-DR4 is a predisposing factor of rheumatoid arthritis. This patient was HLA-B27 and HLA-DR4 positive, and ankylosing spondylitis manifested before rheumatoid arthritis. After disease modifying anti-rheumatic drugs successfully arrested ankylosing spondylitis activity the patient conceived and delivered a healthy baby. One year later, she developed peripheral polyarthritis and was diagnosed with rheumatoid arthritis. We hypothesized that pregnancy may be one of the environmental factors that can activate rheumatoid arthritis, and that disease modifying anti-rheumatic drugs play an important role in keeping the disease under control.

Efficacy,safety,and cost-effectiveness of triple therapy in preventing relapse in rheumatoid arthritis:A randomized controlled trial(ESCoRT study)

Background:Biological agents,such as tumor necrosis factor inhibitors(TNFi),have been widely used in rheumatoid arthritis(RA)patients and greatly improved goal achievement.The aim of this study was to investigate whether conventional synthetic diseasemodifying anti-rheumatic drugs(csDMARDs)combination was better in reducing relapse than methotrexate(MTX)monotherapy,and more cost-effective than continuing TNFi plus MTX in RA patients who achieved low disease activity(LDA)with TNFi and MTX therapy.Methods:RA patients who failed to csDMARDs received an induction therapy of MTX plus TNFi for maximally 12 weeks.Those achieving LDA in 12 weeks were randomly assigned at a 1:1:1 ratio into three groups:(A)adding hydroxychloroquine and sulfasalazine for the first 12 weeks and then discontinuing TNFi for the following 48 weeks;(B)maintaining TNFi and MTX for 60 weeks;and(C)maintaining TNFi and MTX for the first 12 weeks and then discontinuing TNFi for the following 48 weeks.The primary outcome was relapse.Results:A total of 117 patients were enrolled for induction therapy and 67 patients who achieved LDA within 12 weeks were randomized,with 24,21,and 22 patients in groups A,B,and C,respectively.The relapse rates of groups A and B during the entire 60 weeks were comparable[10/22(45.5%)vs.7/20(35.0%),χ^(2)=0.475,P=0.491],however,significantly lower than that of group C[10/22(45.5%)vs.17/20(85.0%),χ^(2)=5.517,P=0.019;7/20(35.0%)vs.17/20(85.0%),χ^(2)=11.035,P=0.004,respectively].Taking RMB 100,000 Yuan as the threshold of willingness to pay,compared to MTX monotherapy(group C),both TNFi maintenance and triple csDMARDs therapies were cost-effective,but triple csDMARDs therapy was better.Conclusion:For RA patients who have achieved LDA with TNFi and MTX,csDMARDs triple therapy was a cost-effective option in favor of reducing relapse.Trial registration:ClinicalTrials.gov,NCT02320630.