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Annals of the Rheumatic Diseases Jan 2024Since the publication of the EULAR recommendations for the management of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) in 2016, several...
BACKGROUND
Since the publication of the EULAR recommendations for the management of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) in 2016, several randomised clinical trials have been published that have the potential to change clinical care and support the need for an update.
METHODS
Using EULAR standardised operating procedures, the EULAR task force undertook a systematic literature review and sought opinion from 20 experts from 16 countries. We modified existing recommendations and created new recommendations.
RESULTS
Four overarching principles and 17 recommendations were formulated. We recommend biopsies and ANCA testing to assist in establishing a diagnosis of AAV. For remission induction in life-threatening or organ-threatening AAV, we recommend a combination of high-dose glucocorticoids (GCs) in combination with either rituximab or cyclophosphamide. We recommend tapering of the GC dose to a target of 5 mg prednisolone equivalent/day within 4-5 months. Avacopan may be considered as part of a strategy to reduce exposure to GC in granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA). Plasma exchange may be considered in patients with rapidly progressive glomerulonephritis. For remission maintenance of GPA/MPA, we recommend rituximab. In patients with relapsing or refractory eosinophilic GPA, we recommend the use of mepolizumab. Azathioprine and methotrexate are alternatives to biologics for remission maintenance in AAV.
CONCLUSIONS
In the light of recent advancements, these recommendations provide updated guidance on AAV management. As substantial data gaps still exist, informed decision-making between physicians and patients remains of key relevance.
Topics: Humans; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Antibodies, Antineutrophil Cytoplasmic; Azathioprine; Cyclophosphamide; Granulomatosis with Polyangiitis; Microscopic Polyangiitis; Remission Induction; Rituximab; Practice Guidelines as Topic
PubMed: 36927642
DOI: 10.1136/ard-2022-223764 -
The Cochrane Database of Systematic... Jul 2023Psoriasis is an immune-mediated disease with either skin or joints manifestations, or both, and it has a major impact on quality of life. Although there is currently no... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Psoriasis is an immune-mediated disease with either skin or joints manifestations, or both, and it has a major impact on quality of life. Although there is currently no cure for psoriasis, various treatment strategies allow sustained control of disease signs and symptoms. The relative benefit of these treatments remains unclear due to the limited number of trials comparing them directly head-to-head, which is why we chose to conduct a network meta-analysis.
OBJECTIVES
To compare the benefits and harms of non-biological systemic agents, small molecules, and biologics for people with moderate-to-severe psoriasis using a network meta-analysis, and to provide a ranking of these treatments according to their benefits and harms.
SEARCH METHODS
For this update of the living systematic review, we updated our searches of the following databases monthly to October 2022: the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and Embase.
SELECTION CRITERIA
Randomised controlled trials (RCTs) of systemic treatments in adults over 18 years with moderate-to-severe plaque psoriasis, at any stage of treatment, compared to placebo or another active agent. The primary outcomes were: proportion of participants who achieved clear or almost clear skin, that is, at least Psoriasis Area and Severity Index (PASI) 90; proportion of participants with serious adverse events (SAEs) at induction phase (8 to 24 weeks after randomisation).
DATA COLLECTION AND ANALYSIS
We conducted duplicate study selection, data extraction, risk of bias assessment, and analyses. We synthesised data using pairwise and network meta-analysis (NMA) to compare treatments and rank them according to effectiveness (PASI 90 score) and acceptability (inverse of SAEs). We assessed the certainty of NMA evidence for the two primary outcomes and all comparisons using CINeMA, as very low, low, moderate, or high. We contacted study authors when data were unclear or missing. We used the surface under the cumulative ranking curve (SUCRA) to infer treatment hierarchy, from 0% (worst for effectiveness or safety) to 100% (best for effectiveness or safety).
MAIN RESULTS
This update includes an additional 12 studies, taking the total number of included studies to 179, and randomised participants to 62,339, 67.1% men, mainly recruited from hospitals. Average age was 44.6 years, mean PASI score at baseline was 20.4 (range: 9.5 to 39). Most studies were placebo-controlled (56%). We assessed a total of 20 treatments. Most (152) trials were multicentric (two to 231 centres). One-third of the studies (65/179) had high risk of bias, 24 unclear risk, and most (90) low risk. Most studies (138/179) declared funding by a pharmaceutical company, and 24 studies did not report a funding source. Network meta-analysis at class level showed that all interventions (non-biological systemic agents, small molecules, and biological treatments) showed a higher proportion of patients reaching PASI 90 than placebo. Anti-IL17 treatment showed a higher proportion of patients reaching PASI 90 compared to all the interventions. Biologic treatments anti-IL17, anti-IL12/23, anti-IL23, and anti-TNF alpha showed a higher proportion of patients reaching PASI 90 than the non-biological systemic agents. For reaching PASI 90, the most effective drugs when compared to placebo were (SUCRA rank order, all high-certainty evidence): infliximab (risk ratio (RR) 49.16, 95% CI 20.49 to 117.95), bimekizumab (RR 27.86, 95% CI 23.56 to 32.94), ixekizumab (RR 27.35, 95% CI 23.15 to 32.29), risankizumab (RR 26.16, 95% CI 22.03 to 31.07). Clinical effectiveness of these drugs was similar when compared against each other. Bimekizumab and ixekizumab were significantly more likely to reach PASI 90 than secukinumab. Bimekizumab, ixekizumab, and risankizumab were significantly more likely to reach PASI 90 than brodalumab and guselkumab. Infliximab, anti-IL17 drugs (bimekizumab, ixekizumab, secukinumab, and brodalumab), and anti-IL23 drugs except tildrakizumab were significantly more likely to reach PASI 90 than ustekinumab, three anti-TNF alpha agents, and deucravacitinib. Ustekinumab was superior to certolizumab. Adalimumab, tildrakizumab, and ustekinumab were superior to etanercept. No significant difference was shown between apremilast and two non-biological drugs: ciclosporin and methotrexate. We found no significant difference between any of the interventions and the placebo for the risk of SAEs. The risk of SAEs was significantly lower for participants on methotrexate compared with most of the interventions. Nevertheless, the SAE analyses were based on a very low number of events with very low- to moderate-certainty evidence for all the comparisons. The findings therefore have to be viewed with caution. For other efficacy outcomes (PASI 75 and Physician Global Assessment (PGA) 0/1), the results were similar to the results for PASI 90. Information on quality of life was often poorly reported and was absent for several of the interventions.
AUTHORS' CONCLUSIONS
Our review shows that, compared to placebo, the biologics infliximab, bimekizumab, ixekizumab, and risankizumab were the most effective treatments for achieving PASI 90 in people with moderate-to-severe psoriasis on the basis of high-certainty evidence. This NMA evidence is limited to induction therapy (outcomes measured from 8 to 24 weeks after randomisation), and is not sufficient for evaluating longer-term outcomes in this chronic disease. Moreover, we found low numbers of studies for some of the interventions, and the young age (mean 44.6 years) and high level of disease severity (PASI 20.4 at baseline) may not be typical of patients seen in daily clinical practice. We found no significant difference in the assessed interventions and placebo in terms of SAEs, and the safety evidence for most interventions was very low to moderate quality. More randomised trials directly comparing active agents are needed, and these should include systematic subgroup analyses (sex, age, ethnicity, comorbidities, psoriatic arthritis). To provide long-term information on the safety of treatments included in this review, an evaluation of non-randomised studies is needed. Editorial note: This is a living systematic review. Living systematic reviews offer a new approach to review updating, in which the review is continually updated, incorporating relevant new evidence as it becomes available. Please refer to the Cochrane Database of Systematic Reviews for the current status of this review.
Topics: Adult; Male; Humans; Female; Ustekinumab; Methotrexate; Infliximab; Network Meta-Analysis; Systematic Reviews as Topic; Psoriasis; Tumor Necrosis Factor-alpha; Biological Products
PubMed: 37436070
DOI: 10.1002/14651858.CD011535.pub6 -
Clinical Reviews in Allergy & Immunology Aug 2023Vernal keratoconjunctivitis (VKC) is a chronic, bilateral corneal and conjunctival problem which typically presents in young individuals. VKC is characterized by... (Review)
Review
Vernal keratoconjunctivitis (VKC) is a chronic, bilateral corneal and conjunctival problem which typically presents in young individuals. VKC is characterized by itching, photophobia, white mucous discharge, lacrimation, foreign body sensation, and pain due to corneal involvement of shield ulcers. Vernal keratoconjunctivitis is categorized within ocular diseases. The diagnosis is clinical, as no sure biomarkers pathognomonic of the disease have yet been identified. The VKC therapy relies on different types of drugs, from antihistamines and topical steroids to cyclosporine or tacrolimus eye drops. In extremely rare cases, there is also the need for surgical treatment for the debridement of ulcers, as well as for advanced glaucoma and cataracts, caused by excessive prolonged use of steroid eye drops. We performed a systematic review of the literature, according to PRISMA guideline recommendations. We searched the PubMed database from January 2016 to June 2023. Search terms were Vernal, Vernal keratoconjunctivitis, and VKC. We initially identified 211 articles. After the screening process, 168 studies were eligible according to our criteria and were included in the review. In this study, we performed a systematic literature review to provide a comprehensive overview of currently available diagnostic methods, management of VKC, and its treatments.
Topics: Humans; Conjunctivitis, Allergic; Ulcer; Cyclosporine; Tacrolimus; Ophthalmic Solutions
PubMed: 37658939
DOI: 10.1007/s12016-023-08970-4 -
Osteoarthritis and Cartilage Oct 2023Guideline adherence for hip and knee osteoarthritis management is often poor, possibly related to the quality and/or inconsistent recommendations. This systematic review... (Review)
Review
OBJECTIVES
Guideline adherence for hip and knee osteoarthritis management is often poor, possibly related to the quality and/or inconsistent recommendations. This systematic review of hip and knee osteoarthritis guidelines aimed to appraise the quality and consistency in recommendations across higher-quality guidelines.
METHODS
Eight databases, guideline repositories, and professional associations websites were searched on 27/10/2022. Guideline quality was appraised using the Appraisal of Guidelines for Research and Evaluation II (AGREE II tool) (six domains). Higher quality was defined as scoring ≥60% for domains 3 (rigour of development), 6 (editorial independence), plus one other. Consistency in recommendations across higher-quality guidelines was reported descriptively. This review was registered prospectively (CRD42021216154).
RESULTS
Seven higher-quality and 18 lesser-quality guidelines were included. AGREE II domain scores for higher-quality guidelines were > 60% except for applicability (average 46%). Higher-quality guidelines consistently recommended in favour of education, exercise, and weight management and non-steroidal anti-inflammatory drugs (hip and knee), and intra-articular corticosteroid injections (knee). Higher quality guidelines consistently recommended against hyaluronic acid (hip) and stem cell (hip and knee) injections. Other pharmacological recommendations in higher-quality guidelines (e.g., paracetamol, intra-articular corticosteroid (hip), hyaluronic acid (knee)) and adjunctive treatments (e.g., acupuncture) were less consistent. Arthroscopy was consistently recommended against in higher-quality guidelines. No higher-quality guidelines considered arthroplasty.
CONCLUSION
Higher-quality guidelines for hip and knee osteoarthritis consistently recommend clinicians implement exercise, education, and weight management, alongside consideration of Non-Steroidal Anti-Inflammatory Drugs and intra-articular corticosteroid injections (knee). Lack of consensus on some pharmacological options and adjunctive treatments creates challenges for guideline adherence. Future guidelines must prioritise providing implementation guidance, considering consistently low applicability scores.
Topics: Humans; Osteoarthritis, Knee; Hyaluronic Acid; Osteoarthritis, Hip; Anti-Inflammatory Agents, Non-Steroidal; Adrenal Cortex Hormones
PubMed: 37394226
DOI: 10.1016/j.joca.2023.05.015 -
Journal of the American Academy of... Aug 2023
Meta-Analysis
Comparative efficacy of biologics and oral agents in palmoplantar psoriasis and palmoplantar pustulosis: A systematic review and network meta-analysis of randomized clinical trials.
Topics: Humans; Biological Products; Network Meta-Analysis; Randomized Controlled Trials as Topic; Psoriasis; Administration, Oral; Treatment Outcome; Ustekinumab; Severity of Illness Index; Adalimumab; Etanercept; Dermatologic Agents
PubMed: 37121476
DOI: 10.1016/j.jaad.2023.04.043 -
Arthritis Care & Research Aug 2023To develop initial American College of Rheumatology (ACR) guidelines on the use of exercise, rehabilitation, diet, and additional interventions in conjunction with...
OBJECTIVE
To develop initial American College of Rheumatology (ACR) guidelines on the use of exercise, rehabilitation, diet, and additional interventions in conjunction with disease-modifying antirheumatic drugs (DMARDs) as part of an integrative management approach for people with rheumatoid arthritis (RA).
METHODS
An interprofessional guideline development group constructed clinically relevant Population, Intervention, Comparator, and Outcome (PICO) questions. A literature review team then completed a systematic literature review and applied the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to rate the certainty of evidence. An interprofessional Voting Panel (n = 20 participants) that included 3 individuals with RA achieved consensus on the direction (for or against) and strength (strong or conditional) of recommendations.
RESULTS
The Voting Panel achieved consensus on 28 recommendations for the use of integrative interventions in conjunction with DMARDs for the management of RA. Consistent engagement in exercise received a strong recommendation. Of 27 conditional recommendations, 4 pertained to exercise, 13 to rehabilitation, 3 to diet, and 7 to additional integrative interventions. These recommendations are specific to RA management, recognizing that other medical indications and general health benefits may exist for many of these interventions.
CONCLUSION
This guideline provides initial ACR recommendations on integrative interventions for the management of RA to accompany DMARD treatments. The broad range of interventions included in these recommendations illustrates the importance of an interprofessional, team-based approach to RA management. The conditional nature of most recommendations requires clinicians to engage persons with RA in shared decision-making when applying these recommendations.
Topics: Humans; United States; Rheumatology; Arthritis, Rheumatoid; Antirheumatic Agents; Diet; Exercise Therapy
PubMed: 37227116
DOI: 10.1002/acr.25117 -
Clinical Rheumatology Sep 2023Systematic r eview to evaluate the quality of the clinical practice guidelines (CPG) for rheumatoid arthritis (RA) management and to provide a synthesis of high-quality... (Review)
Review
Systematic r eview to evaluate the quality of the clinical practice guidelines (CPG) for rheumatoid arthritis (RA) management and to provide a synthesis of high-quality CPG recommendations, highlighting areas of consistency, and inconsistency. Electronic searches of five databases and four online guideline repositories were performed. RA management CPGs were eligible for inclusion if they were written in English and published between January 2015 and February 2022; focused on adults ≥ 18 years of age; met the criteria of a CPG as defined by the Institute of Medicine; and were rated as high quality on the Appraisal of Guidelines for Research and Evaluation II instrument. RA CPGs were excluded if they required additional payment to access; only addressed recommendations for the system/organization of care and did not include interventional management recommendations; and/or included other arthritic conditions. Of 27 CPGs identified, 13 CPGs met eligibility criteria and were included. Non-pharmacological care should include patient education, patient-centered care, shared decision-making, exercise, orthoses, and a multi-disciplinary approach to care. Pharmacological care should include conventional synthetic disease modifying anti-rheumatic drugs (DMARDs), with methotrexate as the first-line choice. If monotherapy conventional synthetic DMARDs fail to achieve a treatment target, this should be followed by combination therapy conventional synthetic DMARDs (leflunomide, sulfasalazine, hydroxychloroquine), biologic DMARDS and targeted synthetic DMARDS. Management should also include monitoring, pre-treatment investigations and vaccinations, and screening for tuberculosis and hepatitis. Surgical care should be recommended if non-surgical care fails. This synthesis offers clear guidance of evidence-based RA care to healthcare providers. TRIAL REGISTRATION: The protocol for this review was registered with Open Science Framework ( https://doi.org/10.17605/OSF.IO/UB3Y7 ).
Topics: Adult; Humans; Antirheumatic Agents; Arthritis, Rheumatoid; Hydroxychloroquine; Methotrexate; Sulfasalazine; Practice Guidelines as Topic
PubMed: 37291382
DOI: 10.1007/s10067-023-06654-0 -
Expert Review of Clinical Immunology 2023Palmoplantar psoriasis (PP) represents a localized type of disease. While controversy over its' classification exists, a hyperkeratotic type, a pustular type and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Palmoplantar psoriasis (PP) represents a localized type of disease. While controversy over its' classification exists, a hyperkeratotic type, a pustular type and palmoplantar pustulosis (PPP) have been recognized. PP management is regularly supported by biologic agents. Our study aimed to review and synthesize available data regarding the efficacy of approved biologics for PP and PPP.
RESEARCH DESIGN AND METHODS
A literature search was conducted in PubMed, CENTRAL, Scopus, and ClinicalTrilas.gov. Utilizing random-effects inverse-variance frequentist network meta-analyses (NMAs), we ranked interventions. The proportion of participants with cleared skin was the primary outcome. Fifty and 75% improvement in palmoplantar psoriasis area severity index (PPASI) were also explored (PPASI50, PPASI75).
RESULTS
In total, 15 randomized controlled trials (RCTs) exploring the efficacy of on-label adalimumab, bimekizumab, etanercept, guselkumab, infliximab, ixekizumab, secukinumab, and ustekinumab were included. Data for PP were synthesized. Every biologic agent examined, except from infliximab, outperformed placebo. On-label secukinumab exhibited the highest probability of inducing complete resolution. Ixekizumab and infliximab ranked best on inducing PPASI50 and PPASI75. Our review supports that guselkumab is effective for PPP.
CONCLUSIONS
Secukinumab, ixekizumab and infliximab are effective for PP. Research is warranted to produce evidence about the efficacy of biologics in PP and PPP.
Topics: Humans; Infliximab; Network Meta-Analysis; Biological Factors; Psoriasis; Biological Products; Severity of Illness Index; Treatment Outcome
PubMed: 37842734
DOI: 10.1080/1744666X.2023.2272049 -
Annals of the Rheumatic Diseases May 2024New modes of action and more data on the efficacy and safety of existing drugs in psoriatic arthritis (PsA) required an update of the EULAR 2019 recommendations for the...
OBJECTIVE
New modes of action and more data on the efficacy and safety of existing drugs in psoriatic arthritis (PsA) required an update of the EULAR 2019 recommendations for the pharmacological treatment of PsA.
METHODS
Following EULAR standardised operating procedures, the process included a systematic literature review and a consensus meeting of 36 international experts in April 2023. Levels of evidence and grades of recommendations were determined.
RESULTS
The updated recommendations comprise 7 overarching principles and 11 recommendations, and provide a treatment strategy for pharmacological therapies. Non-steroidal anti-inflammatory drugs should be used in monotherapy only for mild PsA and in the short term; oral glucocorticoids are not recommended. In patients with peripheral arthritis, rapid initiation of conventional synthetic disease-modifying antirheumatic drugs is recommended and methotrexate preferred. If the treatment target is not achieved with this strategy, a biological disease-modifying antirheumatic drug (bDMARD) should be initiated, without preference among modes of action. Relevant skin psoriasis should orient towards bDMARDs targeting interleukin (IL)-23p40, IL-23p19, IL-17A and IL-17A/F inhibitors. In case of predominant axial or entheseal disease, an algorithm is also proposed. Use of Janus kinase inhibitors is proposed primarily after bDMARD failure, taking relevant risk factors into account, or in case bDMARDs are not an appropriate choice. Inflammatory bowel disease and uveitis, if present, should influence drug choices, with monoclonal tumour necrosis factor inhibitors proposed. Drug switches and tapering in sustained remission are also addressed.
CONCLUSION
These updated recommendations integrate all currently available drugs in a practical and progressive approach, which will be helpful in the pharmacological management of PsA.
Topics: Arthritis, Psoriatic; Humans; Antirheumatic Agents; Anti-Inflammatory Agents, Non-Steroidal; Methotrexate; Biological Products
PubMed: 38499325
DOI: 10.1136/ard-2024-225531 -
BMJ (Clinical Research Ed.) Dec 2023What is the comparative effectiveness of available therapies for chronic pain associated with temporomandibular disorders (TMD)? (Meta-Analysis)
Meta-Analysis
CLINICAL QUESTION
What is the comparative effectiveness of available therapies for chronic pain associated with temporomandibular disorders (TMD)?
CURRENT PRACTICE
TMD are the second most common musculoskeletal chronic pain disorder after low back pain, affecting 6-9% of adults globally. TMD are associated with pain affecting the jaw and associated structures and may present with headaches, earache, clicking, popping, or crackling sounds in the temporomandibular joint, and impaired mandibular function. Current clinical practice guidelines are largely consensus-based and provide inconsistent recommendations.
RECOMMENDATIONS
For patients living with chronic pain (≥3 months) associated with TMD, and compared with placebo or sham procedures, the guideline panel issued: (1) strong recommendations in favour of cognitive behavioural therapy (CBT) with or without biofeedback or relaxation therapy, therapist-assisted mobilisation, manual trigger point therapy, supervised postural exercise, supervised jaw exercise and stretching with or without manual trigger point therapy, and usual care (such as home exercises, stretching, reassurance, and education); (2) conditional recommendations in favour of manipulation, supervised jaw exercise with mobilisation, CBT with non-steroidal anti-inflammatory drugs (NSAIDS), manipulation with postural exercise, and acupuncture; (3) conditional recommendations against reversible occlusal splints (alone or in combination with other interventions), arthrocentesis (alone or in combination with other interventions), cartilage supplement with or without hyaluronic acid injection, low level laser therapy (alone or in combination with other interventions), transcutaneous electrical nerve stimulation, gabapentin, botulinum toxin injection, hyaluronic acid injection, relaxation therapy, trigger point injection, acetaminophen (with or without muscle relaxants or NSAIDS), topical capsaicin, biofeedback, corticosteroid injection (with or without NSAIDS), benzodiazepines, and β blockers; and (4) strong recommendations against irreversible oral splints, discectomy, and NSAIDS with opioids.
HOW THIS GUIDELINE WAS CREATED
An international guideline development panel including patients, clinicians with content expertise, and methodologists produced these recommendations in adherence with standards for trustworthy guidelines using the GRADE approach. The MAGIC Evidence Ecosystem Foundation (MAGIC) provided methodological support. The panel approached the formulation of recommendations from the perspective of patients, rather than a population or health system perspective.
THE EVIDENCE
Recommendations are informed by a linked systematic review and network meta-analysis summarising the current body of evidence for benefits and harms of conservative, pharmacologic, and invasive interventions for chronic pain secondary to TMD.
UNDERSTANDING THE RECOMMENDATION
These recommendations apply to patients living with chronic pain (≥3 months duration) associated with TMD as a group of conditions, and do not apply to the management of acute TMD pain. When considering management options, clinicians and patients should first consider strongly recommended interventions, then those conditionally recommended in favour, then conditionally against. In doing so, shared decision making is essential to ensure patients make choices that reflect their values and preference, availability of interventions, and what they may have already tried. Further research is warranted and may alter recommendations in the future.
Topics: Adult; Humans; Anti-Inflammatory Agents, Non-Steroidal; Chronic Pain; Hyaluronic Acid; Temporomandibular Joint Disorders
PubMed: 38101929
DOI: 10.1136/bmj-2023-076227