New insights and long-term safety of tocilizumab in rheumatoid arthritis

Rheumatoid arthritis is a leading musculoskeletal cause of disability in Western society. Therapeutic options have expanded rapidly with the advent of biological agents as treatment options. One of these, tocilizumab, targets the interleukin-6 receptor and has been approved since the late 2000s in many jurisdictions. This approval was based on 6–12 month trials. It is now appropriate to look at longer-term studies and what new insights they have provided into this agent. Data are based largely on observational studies with their well-known limitations as well as some further randomized trials and provide a number of important observations regarding both efficacy and safety. In conclusion, the longer-term data suggest tocilizumab efficacy increases over time for both signs and symptoms and radiographic change. It is also corticosteroid sparing. The safety data are consistent with the shorter-term trials and are largely reassuring but some questions still remain over cardiovascular safety and cancer risk.

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Treatment Options for Rheumatoid Arthritis: Celecoxib, Leflunomide, Etanercept, and Infliximab

Annals of Pharmacotherapy ◽

10.1345/aph.19344 ◽

2000 ◽

Vol 34 (6) ◽

pp. 743-760 ◽

Cited By ~ 19

Author(s):

Brigitte T Luong ◽

Barbara S Chong ◽

Dionne M Lowder

Keyword(s):

Rheumatoid Arthritis ◽

English Language ◽

Data Extraction ◽

Treatment Options ◽

Nonsteroidal Antiinflammatory Drugs ◽

Antiinflammatory Drugs ◽

Safety And Efficacy ◽

Medline Search ◽

Pertinent Data

OBJECTIVE: To review new pharmacologic agents approved for use in the management of rheumatoid arthritis (RA). DATA SOURCES: A MEDLINE search (1966–January 2000) was conducted to identify English-language literature available on the pharmacotherapy of RA, focusing on celecoxib, leflunomide, etanercept, and infliximab. These articles, relevant abstracts, and data provided by the manufacturers were used to collect pertinent data. STUDY SELECTION: All controlled and uncontrolled trials were reviewed. DATA EXTRACTION: Agents were reviewed with regard to mechanism of action, efficacy, drug interactions, pharmacokinetics, dosing, precautions/contraindications, adverse effects, and cost. DATA SYNTHESIS: Traditional pharmacologic treatments for RA have been limited by toxicity, loss of efficacy, or both. Increasing discoveries into the mechanisms of inflammation in RA have led to the development of new agents in hopes of addressing these limitations. With the development of celecoxib, a selective cyclooxygenase-2 inhibitor, the potential exists to minimize the gastrotoxicity associated with nonsteroidal antiinflammatory drugs. Leflunomide has been shown to be equal to or less efficacious than methotrexate, and may be beneficial as a second-line disease-modifying antirheumatic drug (DMARD). The biologic response modifiers, etanercept and infliximab, are alternatives that have shown benefit alone or in combination with methotrexate. However, they should be reserved for patients who fail to respond to DMARD therapy. Further studies should be conducted to evaluate the long-term safety and efficacy of these agents as well as their role in combination therapy. CONCLUSIONS: Celecoxib, leflunomide, etanercept, and infliximab are the newest agents approved for RA. Clinical trials have shown that these agents are beneficial in the treatment of RA; however, long-term safety and efficacy data are lacking.

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Long-term Use of Aspirin and Age-related Macular Degeneration

US Ophthalmic Review ◽

10.17925/usor.2013.06.02.144 ◽

2013 ◽

Vol 06 (02) ◽

pp. 144 ◽

Cited By ~ 1

Author(s):

William G Christen ◽

Emily Y Chew ◽

◽

Keyword(s):

Macular Degeneration ◽

Observational Studies ◽

Randomized Trials ◽

Epidemiologic Studies ◽

Age Related Macular Degeneration ◽

Neovascular Amd ◽

Age Related ◽

The Us ◽

Regular Aspirin

Recent findings from observational epidemiologic studies have raised concern about a possible adverse effect of regular aspirin use in age-related macular degeneration (AMD), and in particular neovascular AMD, which is the leading cause of severe irreversible blindness in the US. In this report, we consider these findings in light of the relative strengths and limitations of observational studies and randomized trials. While the findings are important and warrant further investigation, the inherent limitations of observation studies, most notably uncontrolled confounding, preclude an interpretation of causality. Alternatively, the most reliable evidence with which to evaluate the effects of regular aspirin use in AMD will derive from well-designed randomized trials of sufficient size and duration.

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Does immunological remission, defined as disappearance of autoantibodies, occur with current treatment strategies? A long-term follow-up study in rheumatoid arthritis patients who achieved sustained DMARD-free status

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2018-214868 ◽

2019 ◽

Vol 78 (11) ◽

pp. 1497-1504 ◽

Cited By ~ 3

Author(s):

Debbie M Boeters ◽

Leonie E Burgers ◽

René EM Toes ◽

Annette van der Helm-van Mil

Keyword(s):

Rheumatoid Arthritis ◽

Treatment Strategies ◽

Signs And Symptoms ◽

Current Treatment ◽

Dmard Therapy ◽

Before And After ◽

Long Term Follow Up ◽

Free Status

ObjectivesSustained disease-modifying antirheumatic drug (DMARD)-free status, the sustained absence of synovitis after cessation of DMARD therapy, is infrequent in autoantibody-positive rheumatoid arthritis (RA), but approximates cure (ie, disappearance of signs and symptoms). It was recently suggested that immunological remission, defined as disappearance of anti-citrullinated protein antibodies (ACPA) and rheumatoid factor (RF), underlies this outcome. Therefore, this long-term observational study determined if autoantibodies disappear in RA patients who achieved sustained DMARD-free remission.MethodsWe studied 95 ACPA-positive and/or RF-positive RA patients who achieved DMARD-free remission after median 4.8 years and kept this status for the remaining follow-up (median 4.2 years). Additionally, 21 autoantibody-positive RA patients with a late flare, defined as recurrence of clinical synovitis after a DMARD-free status of ≥1 year, and 45 autoantibody-positive RA patients who were unable to stop DMARD therapy (during median 10 years) were studied. Anti-cyclic citrullinated peptide 2 (anti-CCP2) IgG, IgM and RF IgM levels were measured in 587 samples obtained at diagnosis, before and after achieving DMARD-free remission.Results13% of anti-CCP2 IgG-positive RA patients had seroreverted when achieving remission. In RA patients with a flare and persistent disease this was 8% and 6%, respectively (p=0.63). For anti-CCP2 IgM and RF IgM, similar results were observed. Evaluating the estimated slope of serially measured levels revealed that RF levels decreased more in patients with than without remission (p<0.001); the course of anti-CCP2 levels was not different (p=0.66).ConclusionsSustained DMARD-free status in autoantibody-positive RA was not paralleled by an increased frequency of reversion to autoantibody negativity. This form of immunological remission may therefore not be a treatment target in patients with classified RA.

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Irreparable rotator cuff tears: Current treatment options

Orthopedic Reviews ◽

10.4081/or.2019.8146 ◽

2019 ◽

Vol 11 (3) ◽

Cited By ~ 1

Author(s):

Tristan Juhan ◽

Michael Stone ◽

Omid Jalali ◽

Will Curtis ◽

John Prodromo ◽

...

Keyword(s):

Rotator Cuff ◽

Reverse Shoulder Arthroplasty ◽

Treatment Options ◽

Current Treatment ◽

Rotator Cuff Tears ◽

Biceps Tenotomy ◽

Common Causes ◽

Cuff Repair ◽

Term Data

Rotator cuff disease is one of the most common causes of shoulder pain, yet controversy still exists regarding treatment of “irreparable” tears. Nonoperative management, including physical therapy and steroid injections, should be reserved for those without significant pain or functional impairment. Debridement may be used for low-demand patients, and should be performed with partial cuff repair, subacromial decompression, and/or acromioplasty to maximize outcomes. Biceps tenotomy and/or tenodesis have been shown to reduce postoperative pain and improve satisfaction when performed in conjunction with rotator cuff repairs, with no difference in functional outcome comparatively. Tendon transfers have been advocated with the potential benefit to improve function and decrease pain. More recently, extracellular matrix and human-derived dermal allografts have been used off-label as patch grafts in irreparable tears. Superior capsular reconstructive techniques and subacromial balloon spacers serve a similar function by acting to depress the humeral head in a cuff-deficient shoulder, however long-term data is needed before widespread adoption of these procedures. Finally, reverse shoulder arthroplasty serves as a salvage option for low demand elderly patients.

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Neuromodulatory Approaches to the Management of Medically Refractory Cluster Headache

European Neurological Review ◽

10.17925/enr.2010.05.01.97 ◽

2010 ◽

Vol 5 (1) ◽

pp. 97

Author(s):

Arne May ◽

Peter J Goadsby ◽

◽

Keyword(s):

Cluster Headache ◽

Treatment Options ◽

Primary Headache ◽

Chronic Cluster Headache ◽

Primary Headache Disorders ◽

Greater Occipital Nerve ◽

Term Data ◽

Deep Brain ◽

Stimulation Of

The trigeminal autonomic cephalalgias are a group of primary headache disorders characterised by unilateral trigeminal distribution of pain that occurs in association with ipsilateral cranial autonomic features. The most prominent one is cluster headache, a dreadful disease with excrutiating pain attacks. These attacks last no longer than two hours but may occur several times per day. It is mandatory to find an efficient therapy for these patients, but some are unresponsive to all treatments. In these intractable cases invasive procedures are introduced, but the available evidence (while conflicting) illustrates that trigeminal denervation may not be effective in preventing the headache attacks or autonomic symptoms of chronic cluster headache. Modern neurostimulating approaches, such as stimulation of the greater occipital nerve and hypothalamic deep brain stimulation, supersede neurodestructive procedures. Both stimulation methods are exquisite and potentially lifesaving treatment options in otherwise intractable patients, but they need to be better characterised and further long-term data are needed.

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Outcomes Reported in Prospective Long‐Term Observational Studies and Registries of Patients with Rheumatoid Arthritis Worldwide: An OMERACT Systematic Review

Arthritis Care & Research ◽

10.1002/acr.24163 ◽

2020 ◽

Author(s):

Maria A. Lopez‐Olivo ◽

Richard J. Zogala ◽

Jude des Bordes ◽

Natalia V. Zamora ◽

Robin Christensen ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Systematic Review ◽

Observational Studies

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Hypothenar hammer syndrome

VASA ◽

10.1024/0301-1526/a000427 ◽

2015 ◽

Vol 44 (3) ◽

pp. 0179-0185 ◽

Cited By ~ 4

Author(s):

Angelika Schröttle ◽

Michael Czihal ◽

Christian Lottspeich ◽

Peter Kuhlencordt ◽

Dennis Nowak ◽

...

Keyword(s):

Randomized Trials ◽

Treatment Options ◽

Case Series ◽

Duplex Sonography ◽

Standard Test ◽

Basic Principles ◽

Routine Diagnostics ◽

Hypothenar Hammer Syndrome ◽

Gold Standard Test

The diagnosis of hypothenar hammer syndrome (HHS) should be considered in the case of hand ischemia in people who occupationally or recreationally use the hypothenar region literally as a hammer. Routine diagnostics should consist of physical examination including Allens test, acral plethysmography and duplex sonography. According to the prevailing opinion angiography remains the «gold standard test» for establishing the diagnosis of HHS. Early diagnosis allows more effective therapeutic strategies and is important to prevent long-term negative medical sequelae. Several basic principles apply to all patients, for example hand protection and smoking cessation. The optimal treatment options, particularly the indication for surgery, remain controversial due to a lack of sound data from case series or prospective randomized trials.

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Sensitivity to change of the Health Assessment Questionnaire (HAQ) and other clinical and health status measures in rheumatoid arthritis results of short-term clinical trials and observational studies versus long-term observational studies

Arthritis & Rheumatism ◽

10.1002/art.1790050304 ◽

1992 ◽

Vol 5 (3) ◽

pp. 130-136 ◽

Cited By ~ 66

Author(s):

Donna J. Hawley ◽

Frederick Wolfe

Keyword(s):

Rheumatoid Arthritis ◽

Clinical Trials ◽

Observational Studies ◽

Health Assessment Questionnaire ◽

Health Assessment ◽

Sensitivity To Change ◽

Short Term ◽

Health Status Measures ◽

Assessment Questionnaire

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Infections

Operative Plastic Surgery ◽

10.1093/med/9780190499075.003.0099 ◽

2019 ◽

pp. 995-1002

Author(s):

Scott D. Oates

Keyword(s):

Human Activities ◽

Surgical Intervention ◽

Fungal Infections ◽

Treatment Options ◽

Healthcare Providers ◽

Signs And Symptoms ◽

The Body ◽

Early Surgical Intervention

Because of their exposed nature during human activities, infections of the hand are common. The anatomy of the hand and fingers also lends itself to unique types of infections that do not occur in other areas of the body, such as paronychia, felons, and fungal infections. Because of these unique types of infections, early surgical intervention is often necessary to prevent long-term functional sequelae. This requires healthcare providers to be knowledgeable of the signs and symptoms of these distinct infections in order to effectively treat these patients. This chapter describes many common hand infections and their treatment options.

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