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Clinical and Experimental Rheumatology May 2022Due to the rarity of relapsing polychondritis (RP), no randomised clinical trial has been conducted to date and treatment remains empirical. We performed a systematic... (Review)
Review
OBJECTIVES
Due to the rarity of relapsing polychondritis (RP), no randomised clinical trial has been conducted to date and treatment remains empirical. We performed a systematic literature review to assess the efficacy of the main conventional immunosuppressants and biotherapies used in RP.
METHODS
We searched MEDLINE for original articles without language restriction. Abstracts from American College of Rheumatology (ACR) and European Alliance of Associations for Rheumatology (EULAR) were also considered for inclusion. Observational studies and clinical trials reporting on the efficacy of conventional immunosuppressants and biotherapies in adult patients with RP were selected and pooled response rates for each treatment were computed.
RESULTS
Of 304 articles and abstracts identified, 31 underwent full-text review, and 11 were included. The studies involved a total of 177 patients, exposed to a total of 247 lines of treatments. The main treatments studied (by number of lines) were: TNF inhibitors (TNFi), n=92; methotrexate (MTX), n=38; tocilizumab (TCZ), n=26; anakinra (ANA), n=21; rituximab (RTX), n=16; abatacept (ABT), n=14; cyclophosphamide (CYC), n=14; azathioprine (AZA), n=13. The pooled response rates across studies were: 72% [95% CI: 42-95] for ABT, 66% [95% CI: 49-82] for TCZ, 64% [95% CI: 53-74] for TNFi, 56% [95% CI: 37-73] for MTX, 47% [95% CI: 26-68] for ANA, 43% [95% CI: 20-68] for RTX. Based on more limited data, response rates for AZA and CYC ranged from 38 to 100% and from 25 to 100%, respectively.
CONCLUSIONS
In this systematic review of available evidence regarding the treatment of relapsing polychondritis, ABT, TCZ and TNFi were the drugs associated with the best outcomes. ABT efficacy must be interpreted in light of the small number of patients treated. While MTX had slightly less efficacy, it is one of the drugs for which data are the most robust.
Topics: Abatacept; Adult; Antirheumatic Agents; Arthritis, Rheumatoid; Humans; Immunosuppressive Agents; Methotrexate; Polychondritis, Relapsing; Rituximab; Tumor Necrosis Factor Inhibitors
PubMed: 35238756
DOI: 10.55563/clinexprheumatol/h9gq1o -
Autoimmunity Reviews Jun 2021The primary vasculitides constitute a heterogeneous group of immune mediated diseases of incompletely understood pathogenesis currently classified by the size of blood... (Review)
Review
The primary vasculitides constitute a heterogeneous group of immune mediated diseases of incompletely understood pathogenesis currently classified by the size of blood vessels affected (Chapel Hill classification). In recent years, several drugs with well-characterized immunological targets have been tested in clinical trials in large vessel vasculitis and small vessel vasculitis. Such trials provide "reverse translational" or bedside to bench information about underlying pathogenic mechanisms. Therefore, the aim of this systematic literature review was to examine the evidence base for a more refined mechanistic immunological classification of vasculitis. A total of 40 studies (20 randomized controlled trials (RCTs), 16 prospective studies, 1 retrospective cohort study and 3 case series) were included for full qualitative assessment. RCTs concerning biologic therapy for large vessel vasculitis mainly supports interleukin 6 receptor inhibition (tocilizumab). RCTs concerning biologic therapy for granulomatosis with polyangiitis and microscopic polyangiitis mainly support anti-CD20 treatment (rituximab) and complement inhibition with a small molecule C5a receptor antagonist (avacopan) is an emerging treatment option. The biologic treatment of eosinophilic granulomatosis with polyangiitis is centered around interleukin 5 inhibition (mepolizumab). Studies on tumor necrosis factor alpha inhibition (adalimumab, infliximab, and etanercept) showed negative results in giant cell arteritis but some effect in Takayasu arteritis. Taken together, clinical studies with cytokine and cell specific drugs are dissecting the heterogeneous immunopathogenic mechanisms of vasculitis and support a mechanistic immunological classification. Especially, cytokine antagonism is pointing towards immunological distinctions between eosinophilic granulomatosis with polyangiitis and granulomatosis with polyangiitis/microscopic polyangiitis and differences between giant cell arteritis and Takayasu arteritis.
Topics: Churg-Strauss Syndrome; Etanercept; Giant Cell Arteritis; Granulomatosis with Polyangiitis; Humans; Microscopic Polyangiitis; Randomized Controlled Trials as Topic; Rituximab; Takayasu Arteritis
PubMed: 33872767
DOI: 10.1016/j.autrev.2021.102829 -
Autoimmunity Reviews Jan 2023Rheumatoid arthritis (RA) is an autoimmune disease characterized by symmetrical peripheral polyarthritis in the hands and/or feet, leading to long-term disability if not... (Review)
Review
BACKGROUND
Rheumatoid arthritis (RA) is an autoimmune disease characterized by symmetrical peripheral polyarthritis in the hands and/or feet, leading to long-term disability if not treated effectively. RA is preceded by a preclinical phase, in which genetically predisposed individuals accumulate environmental risk factors, and during which autoimmunity develops, followed by the emergence of non-specific signs and symptoms before arthritis becomes manifest. Early treatment in at-risk individuals - i.e. before the disease is fully established - has the theoretical potential to delay or prevent disease onset, with a positive impact on both patients' life and society.
OBJECTIVES
We aimed to understand the feasibility of preventive treatment in at-risk individuals, taking into account recently performed studies and ongoing clinical trials, as well as patient perspectives.
METHODS
We performed a systematic literature review (SLR) on Medline and Embase, searching articles published between 2010 and 2021 with the following key-words: "Rheumatoid arthritis", "arthralgia", "pre-treatment" or "prevent".
RESULTS
Our SLR identified a total of 1821 articles. Articles were independently screened by two researchers. A total of 14 articles were included after screening, and an additional 8 reports were manually included. We identified ten relevant clinical trials performed in at-risk individuals, or in individuals with undifferentiated inflammatory arthritis. Although no treatment was shown to prevent RA onset, early treatment with rituximab and abatacept delayed onset of full-blown RA, and both conventional and biological disease-modifying anti-rheumatic drugs (DMARDs) decreased disease-related physical limitations and increased DAS28-defined remission, at least temporarily.
CONCLUSIONS
This SLR demonstrates that early treatment of at-risk individuals may be effective in delaying RA onset, thereby decreasing disease-related limitations in individuals in the pre-clinical phase of RA. Whether this may ultimately lead to prevention of RA remains to be determined.
Topics: Humans; Arthritis, Rheumatoid; Antirheumatic Agents; Abatacept; Rituximab; Autoimmunity
PubMed: 36280095
DOI: 10.1016/j.autrev.2022.103217 -
Annals of the Rheumatic Diseases Jun 2020To inform the 2019 update of the European League against Rheumatism (EULAR) recommendations for the management of rheumatoid arthritis (RA).
Efficacy of pharmacological treatment in rheumatoid arthritis: a systematic literature research informing the 2019 update of the EULAR recommendations for management of rheumatoid arthritis.
OBJECTIVES
To inform the 2019 update of the European League against Rheumatism (EULAR) recommendations for the management of rheumatoid arthritis (RA).
METHODS
A systematic literature research (SLR) to investigate the efficacy of any disease-modifying antirheumatic drug (DMARD) (conventional synthetic (cs)DMARD, biological (b) and biosimilar DMARD, targeted synthetic (ts)DMARD) or glucocorticoid (GC) therapy in patients with RA was done by searching MEDLINE, Embase and the Cochrane Library for articles published between 2016 and 8 March 2019.
RESULTS
234 abstracts were selected for detailed assessment, with 136 finally included. They comprised the efficacy of bDMARDs versus placebo or other bDMARDs, efficacy of Janus kinase (JAK) inhibitors (JAKi) across different patient populations and head-to-head of different bDMARDs versus JAKi or other bDMARDs. Switching of bDMARDs to other bDMARDs or tsDMARDs, strategic trials and tapering studies of bDMARDs, csDMARDs and JAKi were assessed. The drugs evaluated included abatacept, adalimumab, ABT-122, baricitinib, certolizumab pegol, SBI-087, CNTO6785, decernotinib, etanercept, filgotinib, golimumab, GCs, GS-9876, guselkumab, hydroxychloroquine, infliximab, leflunomide, mavrilimumab, methotrexate, olokizumab, otilimab, peficitinib, rituximab, sarilumab, salazopyrine, secukinumab, sirukumab, tacrolimus, tocilizumab, tofacitinib, tregalizumab, upadacitinib, ustekinumab and vobarilizumab. The efficacy of many bDMARDs and tsDMARDs was shown. Switching to another tumour necrosis factor inhibitor (TNFi) or non-TNFi bDMARDs after TNFi treatment failure is efficacious. Tapering of DMARDs is possible in patients achieving long-standing stringent clinical remission; in patients with residual disease activity (including patients in LDA) the risk of flares is increased during the tapering. Biosimilars are non-inferior to their reference products.
CONCLUSION
This SLR informed the task force regarding the evidence base of various therapeutic regimen for the development of the update of EULAR's RA management recommendation.
Topics: Antirheumatic Agents; Arthritis, Rheumatoid; Biological Products; Biosimilar Pharmaceuticals; Drug Substitution; Drug Therapy, Combination; Glucocorticoids; Humans; Janus Kinase Inhibitors; Randomized Controlled Trials as Topic; Synthetic Drugs; Tumor Necrosis Factor-alpha
PubMed: 32033937
DOI: 10.1136/annrheumdis-2019-216656 -
RMD Open Feb 2020Biologic disease-modifying antirheumatic drugs (bDMARDs) and targeted synthetic DMARDs are used in patients with psoriatic arthritis (PsA), but few studies directly... (Comparative Study)
Comparative Study Meta-Analysis
BACKGROUND
Biologic disease-modifying antirheumatic drugs (bDMARDs) and targeted synthetic DMARDs are used in patients with psoriatic arthritis (PsA), but few studies directly compare their clinical efficacy. In such situations, network meta-analysis (NMA) can inform evidence-based decision-making.
OBJECTIVE
To evaluate the comparative efficacy and safety of approved bDMARDs in patients with PsA.
METHODS
Bayesian NMA was conducted to compare the clinical efficacy of bDMARDs at weeks 12‒16 in bDMARD-naïve patients with PsA in terms of American College of Rheumatology (ACR) criteria, Psoriatic Arthritis Response Criteria (PsARC) and Psoriasis Area and Severity Index (PASI). Safety end points were evaluated in the overall mixed population of bDMARD-naive and bDMARD-experienced patients.
RESULTS
For ACR, all treatments except abatacept were statistically superior to placebo. Infliximab was most effective, followed by golimumab and etanercept, which were statistically superior to most other treatments. Ixekizumab 80 mg every 2 weeks (Q2W) was statistically superior to abatacept subcutaneous, apremilast and both regimens of ustekinumab; similar findings were observed for ixekizumab 80 mg Q4W. For PsARC response, ixekizumab did not significantly differ from other therapies, except for golimumab, infliximab and etanercept, which were superior to most other agents including ixekizumab. For PASI response, infliximab was numerically most effective, but was not statistically superior to ixekizumab, which was the next best performing agent. Analysis of safety end points identified few differences between treatments.
CONCLUSION
Our NMA confirms the efficacy and acceptable safety profile of bDMARDs in patients with active PsA. There were generally few statistically significant differences between most treatments.
Topics: Abatacept; Adult; Antibodies, Monoclonal, Humanized; Antirheumatic Agents; Arthritis, Psoriatic; Biological Products; Clinical Decision-Making; Humans; Immune Checkpoint Inhibitors; Interleukin-17; Network Meta-Analysis; Placebos; Safety; Severity of Illness Index; Treatment Outcome
PubMed: 32094304
DOI: 10.1136/rmdopen-2019-001117 -
RMD Open Mar 2022Randomised controlled trials (RCTs) have compared biological and targeted systemic disease-modifying antirheumatic drugs (DMARDS) against placebo in psoriatic arthritis... (Meta-Analysis)
Meta-Analysis
Targeted systemic therapies for psoriatic arthritis: a systematic review and comparative synthesis of short-term articular, dermatological, enthesitis and dactylitis outcomes.
INTRODUCTION
Randomised controlled trials (RCTs) have compared biological and targeted systemic disease-modifying antirheumatic drugs (DMARDS) against placebo in psoriatic arthritis (PsA); few have compared them head to head.
OBJECTIVES
To compare the efficacy and safety of all evaluated DMARDs for active PsA, with a special focus on biological DMARDs (bDMARDs) licensed for PsA or psoriasis.
METHODS
A systematic review identified RCTs and Bayesian network meta-analysis (NMA) compared treatments on efficacy (American College of Rheumatology (ACR) response, Psoriasis Area and Severity Index (PASI) response, resolution of enthesitis and dactylitis) and safety (patients discontinuing due to adverse events (DAE)) outcomes. Subgroup analyses explored ACR response among patients with and without prior biological therapy exposure.
RESULTS
The NMA included 46 studies. Results indicate that some tumour necrosis factor inhibitors (anti-TNFs) may perform numerically, but not significantly, better than interleukin (IL) inhibitors on ACR response but perform worse on PASI response. Few significant differences between bDMARDs on ACR response were observed after subgrouping for prior bDMARD exposure. Guselkumab and IL-17A or IL-17RA inhibitors-brodalumab, ixekizumab, secukinumab-were best on PASI response. These IL-inhibitors and adalimumab were similarly efficacious on resolution of enthesitis and dactylitis. Infliximab with and without methotrexate, certolizumab 400 mg every 4 weeks and tildrakizumab showed the highest rates of DAE; abatacept, golimumab and the IL-inhibitors, the lowest.
CONCLUSIONS
Despite similar efficacy for ACR response, IL-17A and IL-17RA inhibitors and guselkumab offered preferential efficacy to anti-TNFs in skin manifestations, and for enthesitis and dactylitis, thereby supporting drug selection based on predominant clinical phenotype.
Topics: Abatacept; Antirheumatic Agents; Arthritis, Psoriatic; Enthesopathy; Humans
PubMed: 35321874
DOI: 10.1136/rmdopen-2021-002074 -
Frontiers in Immunology 2021Besides recurrent infections, a proportion of patients with Common Variable Immunodeficiency Disorders (CVID) may suffer from immune dysregulation such as... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Besides recurrent infections, a proportion of patients with Common Variable Immunodeficiency Disorders (CVID) may suffer from immune dysregulation such as granulomatous-lymphocytic interstitial lung disease (GLILD). The optimal treatment of this complication is currently unknown. Experienced-based expert opinions have been produced, but a systematic review of published treatment studies is lacking.
GOALS
To summarize and synthesize the published literature on the efficacy of treatments for GLILD in CVID.
METHODS
We performed a systematic review using the PRISMA guidelines. Papers describing treatment and outcomes in CVID patients with radiographic and/or histologic evidence of GLILD were included. Treatment regimens and outcomes of treatment were summarized.
RESULTS
6124 papers were identified and 42, reporting information about 233 patients in total, were included for review. These papers described case series or small, uncontrolled studies of monotherapy with glucocorticoids or other immunosuppressants, rituximab monotherapy or rituximab plus azathioprine, abatacept, or hematopoietic stem cell transplantation (HSCT). Treatment response rates varied widely. Cross-study comparisons were complicated because different treatment regimens, follow-up periods, and outcome measures were used. There was a trend towards more frequent GLILD relapses in patients treated with corticosteroid monotherapy when compared to rituximab-containing treatment regimens based on qualitative endpoints. HSCT is a promising alternative to pharmacological treatment of GLILD, because it has the potential to not only contain symptoms, but also to resolve the underlying pathology. However, mortality, especially among immunocompromised patients, is high.
CONCLUSIONS
We could not draw definitive conclusions regarding optimal pharmacological treatment for GLILD in CVID from the current literature since quantitative, well-controlled evidence was lacking. While HSCT might be considered a treatment option for GLILD in CVID, the risks related to the procedure are high. Our findings highlight the need for further research with uniform, objective and quantifiable endpoints. This should include international registries with standardized data collection including regular pulmonary function tests (with carbon monoxide-diffusion), uniform high-resolution chest CT radiographic scoring, and uniform treatment regimens, to facilitate comparison of treatment outcomes and ultimately randomized clinical trials.
Topics: Clinical Trials as Topic; Combined Modality Therapy; Common Variable Immunodeficiency; Disease Management; Disease Susceptibility; Humans; Lung Diseases, Interstitial; Prognosis
PubMed: 33936030
DOI: 10.3389/fimmu.2021.606099 -
Archives of Rheumatology Jun 2022Biological medications have been used with an increasing frequency to treat rheumatological diseases. Autoimmune events can be induced by these drugs, such as... (Review)
Review
OBJECTIVES
Biological medications have been used with an increasing frequency to treat rheumatological diseases. Autoimmune events can be induced by these drugs, such as psoriasiform lesions, alopecia, lupus and, vasculitis, which more often affects the skin (small-sized vessels) and eventually other organs. In this review, we describe the clinical profile of patients with vasculitis induced by the main biological agents used in rheumatology.
PATIENTS AND METHODS
We performed a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations. The PubMed database was used for searching eligible articles. We included case reports, case series, and letter to the editor of patients on anti-tumor necrosis factor-alpha (anti-TNF-a) molecules, as well as tocilizumab, ustekinumab, secukinumab, rituximab, and abatacept, who had vasculitis induced by these agents.
RESULTS
Eighty-one articles were included for final analysis (n=89). Twenty-seven patients were using infliximab, 20 adalimumab, 18 etanercept, seven secukinumab, four certolizumab, four rituximab, three golimumab, three ustekinumab, two abatacept, and one tocilizumab. Unspecific leukocytoclastic vasculitis (LCV) was the most common type of vasculitis (n=37), followed by anti-neutrophil cytoplasmic antibody (ANCA)- associated vasculitis (n=16). The medication was replaced with another biological molecule in 23 cases, with only four relapses. In six cases, the biological was maintained, but vasculitis worsened/persisted in one case, being necessary drug removal.
CONCLUSION
Infections, infusion reaction, cancer, and autoimmune events are well-known side effects of biological therapy. This review demonstrates that vasculitis is another adverse effect of this type of therapy, particularly the anti-TNF-a molecules, and LCV the most reported type of vasculitis.
PubMed: 36017201
DOI: 10.46497/ArchRheumatol.2022.9049 -
Journal For Immunotherapy of Cancer Jan 2024Immune checkpoint inhibitor (ICI) treatment has become an important therapeutic option for various cancer types. Although the treatment is effective, ICI can...
Immune checkpoint inhibitor (ICI) treatment has become an important therapeutic option for various cancer types. Although the treatment is effective, ICI can overstimulate the patient's immune system, leading to potentially severe immune-related adverse events (irAEs), including hepatitis, colitis, pneumonitis and myocarditis. The initial mainstay of treatments includes the administration of corticosteroids. There is little evidence how to treat steroid-resistant (sr) irAEs. It is mainly based on small case series or single case reports. This systematic review summarizes available evidence about sr-irAEs. We conducted a systematic literature search in PubMed. Additionally, we included European Society for Medical Oncology, Society for Immunotherapy of Cancer, National Comprehensive Cancer Network and American Society of Clinical Oncology Guidelines for irAEs in our assessment. The study population of all selected publications had to include patients with cancer who developed hepatitis, colitis, pneumonitis or myocarditis during or after an immunotherapy treatment and for whom corticosteroid therapy was not sufficient. Our literature search was not restricted to any specific cancer diagnosis. Case reports were also included. There is limited data regarding life-threatening sr-irAEs of colon/liver/lung/heart and the majority of publications are single case reports. Most publications investigated sr colitis (n=26), followed by hepatitis (n=21), pneumonitis (n=17) and myocarditis (n=15). There is most data for mycophenolate mofetil (MMF) to treat sr hepatitis and for infliximab, followed by vedolizumab, to treat sr colitis. Regarding sr pneumonitis there is most data for MMF and intravenous immunoglobulins (IVIG) while data regarding infliximab are conflicting. In sr myocarditis, most evidence is available for the use of abatacept or anti-thymocyte globulin (ATG) (both with or without MMF) or ruxolitinib with abatacept. This review highlights the need for prompt recognition and treatment of sr hepatitis, colitis, pneumonitis and myocarditis. Guideline recommendations for sr situations are not defined precisely. Based on our search, we recommend-as first line treatment-(1) MMF for sr hepatitis, (2) infliximab for sr colitis, followed by vedolizumab, (3) MMF and IVIG for sr pneumonitis and (4) abatacept or ATG (both with or without MMF) or ruxolitinib with abatacept for sr myocarditis. These additional immunosuppressive agents should be initiated promptly if there is no sufficient response to corticosteroids within 3 days.
Topics: Humans; Abatacept; Adrenal Cortex Hormones; Colitis; Hepatitis; Immunoglobulins, Intravenous; Infliximab; Mycophenolic Acid; Myocarditis; Neoplasms; Nitriles; Pneumonia; Pyrazoles; Pyrimidines
PubMed: 38233099
DOI: 10.1136/jitc-2023-007409 -
Clinical and Experimental Immunology Jul 2021Cytotoxic T lymphocyte antigen 4 (CTLA-4) haploinsufficiency (CHAI) and lipopolysaccharide-responsive beige-like anchor (LRBA) deficiency (LATAIE) are newly identified... (Review)
Review
Cytotoxic T lymphocyte antigen 4 (CTLA-4) haploinsufficiency (CHAI) and lipopolysaccharide-responsive beige-like anchor (LRBA) deficiency (LATAIE) are newly identified inborn errors of immunity with shared molecular pathomechanisms and clinical manifestations. In this review, we aimed to provide differential comparisons regarding demographic, clinical, immunological and molecular characteristics between these two similar conditions. A literature search was conducted in PubMed, Web of Science and Scopus databases and included studies were systematically evaluated. Overall, 434 (222 CHAI and 212 LATAIE) patients were found in 101 eligible studies. The CHAI patients were mainly reported from North America and western Europe, while LATAIE patients were predominantly from Asian countries. In CHAI, positive familial history (P < 0·001) and in LATAIE, consanguineous parents (P < 0·001) were more common. In CHAI patients the rates of granulomas (P < 0·001), malignancies (P = 0·001), atopy (P = 0·001), cutaneous disorders (P < 0·001) and neurological (P = 0·002) disorders were higher, while LATAIE patients were more commonly complicated with life-threatening infections (P = 0·002), pneumonia (P = 0·006), ear, nose and throat disorders (P < 0·001), organomegaly (P = 0·023), autoimmune enteropathy (P = 0·038) and growth failure (P < 0·001). Normal lymphocyte subsets and immunoglobulins except low serum levels of CD9 B cells (14·0 versus 38·4%, P < 0·001), natural killer (NK) cells (21 versus 41·1%, P < 0·001), immunoglobulin (Ig)G (46·9 versus 41·1%, P = 0·291) and IgA (54·5 versus 44·7%, P = 0·076) were found in the majority of CHAI and LATAIE patients, respectively. The most frequent biological immunosuppressive agents prescribed for CHAI and LATAIE patients were rituximab and abatacept, respectively. Further investigations into the best conditioning and treatment regimens pre- and post-transplantation are required to improve the survival rate of transplanted CHAI and LATAIE patients.
Topics: Adaptor Proteins, Signal Transducing; CTLA-4 Antigen; Haploinsufficiency; Humans; Immunoglobulins; Immunosuppressive Agents; Lymphocytes
PubMed: 33788257
DOI: 10.1111/cei.13600