Safety of Biologic Therapy : Infections

Safety of Biologic Therapy : Infections

The rash begins in the scalp and spreads distally to the trunk and extremities as a pruritic, maculopapular rash progressing to vesicles before crusting over. A study found that only 60% of obstetrician/gynecologists routinely asked about immunization status during visits. Histopathology of a subepidermal blister demonstrated an eosinophil-rich inflammatory infiltrate in the dermis. Medscape, LLC encourages Authors to identify investigational products or off-label uses of products regulated by the US Food and Drug Administration, at first mention and where appropriate in the content. In this interview, Helen Fosam, PhD, Medscape Rheumatology, spoke with Jonathan Kay, MD, FACP, FACR, Associate Clinical Professor of Medicine, Harvard Medical School, Boston, Massachusetts, on the recent advances with biologic agents targeted at TNF, as illustrated by data presented at the 2008 European League Against Rheumatism (EULAR) meeting. Dr. At 12 months, the mean paired differences (placebo minus cladribine) in EDSS scores were 1.3 (0.3) with 95% confidence interval 0.6–2.

Any especially unusual or aggressive features should cause the clinician to expand the investigation to search for other demyelinating entities, such as neuromyelitis optica (NMO), and other MS mimickers such as lupus, sarcoidosis, Susac syndrome, or central nervous system vasculitis. Many cases of shingles go away by themselves, with or without treatment. The rarity of these events also leads to wide confidence intervals (see Table 1 and Table 2 ), making it difficult to identify a precise increase in risk that a clinician could use in discussions with patients. It is marketed by Ortho Biotech under the name Leustatin. Statins Widely Underused After Acute Coronary Syndrome Registry findings show that 1 in 5 patients eligible for secondary prevention with statins after acute coronary syndrome was not prescribed statins at hospital discharge. Medscape encourages you to complete the Activity Evaluation to provide feedback for future programming. Blood pressure and lipids should be monitored periodically in all women, and appropriate pharmacotherapy should be started when indicated.

Some patients experience long-term pain control with either topical or oral monotherapy with antidepressants, anticonvulsants, or opioids. Caution is, however, recommended when prescribing abatacept for patients with underlying COPD. They found that from 1999 to 2002, hospitalizations fell by 88% and outpatient visits decreased by 59% in all age groups. In contrast, intranasal influenza vaccines contain live attenuated virus and should not be administered during pregnancy. The Nikolsky sign is described as the separation of superficial skin from the deeper dermis with the application of gentle pressure. Medscape requires version 4.x browsers or higher from Microsoft or Netscape. The study by Perez-Zafrilla and colleagues,[2] looking at the Biobadaser Spanish registry, compared the incidence of herpes zoster in patients with RA treated with biologic agents vs other registries of patients not treated with biologic agents.

Safety of Biologic Therapy : Infections
As you move to the right to the dotted line, a light pinch that was mildly painful before injury may now cause severe pain, called hyperalgesia. The mean relapse rate per year at the initiation of therapy was 2.67 ± 0.75. ACTH activates melanocortin receptors (MCRs), including MC2Rs on the adrenal gland, which promotes the synthesis and release of corticosteroids.[18] Although corticosteroids have anti-inflammatory properties,[19] ACTH activates anti-inflammatory pathways through melanocortin receptors such as MC1R and MC3R. Read What Your Physician is Reading on Medscape. Population data on the risk of TB with the use of other TNF inhibitors—which might help to answer this question—are unfortunately limited. Clearly, screening for latent TB before therapy with TNF inhibitors reduces the risk of reactivation of disease, and this practice has become standard for all such agents, including etanercept; indeed, the institution of a screening protocol, with consequent treatment of latent TB, resulted in a 78% reduction in the risk of active TB.[37] Appropriate screening standards vary from country to country, depending on the endemic rate of TB, and might include TB skin testing (TST), serum IFN-γ release assays (IGRA), and/or chest radiographs. When the TST is used for screening in these patients, 5 mm induration should be considered a positive test, given the high-risk nature of treatment with TNF inhibitors.

Clinicians should be aware that both false-negative and false-positive TSTs can occur; IGRA testing might be useful in patients with a history of recent BCG (Bacillus Calmette-Guérin) vaccination, in whom a positive TST is likely to occur. Discordance between TST and IGRA testing, when studied, has been high; a positive result with either test when screening before anti-TNF therapy should be considered evidence of latent TB, and treatment initiated accordingly. This fact enhances its safety. TNF has a role in host defense against various fungal infections, including, but not limited to, candida, coccidioidomycosis, aspergillus and cryptococcus.[39-41] Unsurprisingly, infections with these organisms have been associated with the use of various TNF inhibitors. A case series from Southwestern USA reported 13 cases of coccidioidomycosis infection in patients treated with TNF inhibitors; 12 were treated with infliximab, 1 with etanercept.[42] Cases of disseminated histoplasmosis have also been associated with TNF inhibitors; again, cases have been most frequently associated with infliximab use.[43]Pneumocystis jerovecii infection has also been reported with infliximab, adalimumab and etancercept.[44-46] Although this organism might be a consequential infection, and a Japanese study reported a high carrier rate in the elderly population,[47] no guidelines on P. Influenza infection increases the risk for medical complications. The patient in this case was treated with high-potency topical steroids and experienced a good result.

TNF seems to play a more important part in defense against granulomatous and other opportunistic infections than interleukin signaling pathways do; accordingly, few opportunistic infections have been associated with the use of anakinra or tocilizumab. The authors of this study suggested that the intent-to-treat analysis, which was the prespecified endpoint, failed because there were 3 patients who were randomized but did not receive the study drug. Nonetheless, pain associated with cancer and its treatment can cause direct injury to tissues that leads to acute, localized pain that resolves as tissue heals. In the second 48 week period, both cladribine groups received two courses of cladribine, and the placebo group received 2 courses of placebo. Even so, in a world that now considers “no evidence of disease activity” to be an achievable goal in MS,[27] clinicians need to be vigilant for signs of relapse and ready to aggressively manage these events should they occur. Viral infections have been associated with each of the biologic agents considered in this Review. Given the severity of symptoms and potential complications of Varicella Zoster virus (VZV), Hepatitis B virus (HBV) and the JC virus, we give special attention to these three infections.

Varicella Zoster Virus. VZV infections have been reported with the use of anakinra, abatacept, rituximab or tocilizumab; however, their rates in patients taking these drugs have not, to date, been significantly higher than in the general population.[16,22] Conversely, TNF inhibitors do seem to increase the risk of VZV infection. Data from the BIODABASER database in Spain and the German biologic agent database, RABBIT, have shown a significantly higher risk of VZV reactivation (that is, shingles or herpes zoster) in patients treated with TNF inhibitors than in patients with RA receiving conventional DMARDs.[55,56] In the German study, this significantly increased risk occurred with the use of the monoclonal antibodies (adalimumab and infliximab), but not with etanercept. Hepatitis B.TNF inhibitors and rituximab alike have been associated with reactivation of HBV. We administered 8-methyl-N-vanillyl-noneamide (capsaicin) at doses of 5%-10% to individuals with such disorders in this trial. JC Virus. Progressive multifocal leukoencephalopathy (PML) is a rare, demyelinating disease with a high fatality rate.

It is caused by reactivation of the JC virus, a ubiquitous virus to which 70% or more of the US population has been exposed.[60] PML usually occurs in immunosuppressed individuals, particularly in those with HIV infection. A literature review published in 2009 reported 57 cases of PML in HIV-negative patients receiving rituximab.[61] Of these patients, most received the drug as part of a chemotherapy regimen; however, two individuals were treated for systemic lupus erythematosus (SLE), and one each for RA, immune thrombocytopenia and autoimmune pancytopenia. Unfortunately, no data yet indicate which patients with autoimmune disease are at particular risk of the condition, and no screening tests—or treatment—for JC virus reactivation are available. Kay: The combination of methotrexate and etanercept in active, early, moderate-to-severe RA (COMET study) was presented at EULAR and has recently been published,[18] which shows that in early RA, combination therapy with etanercept plus methotrexate is more effective than treatment with methotrexate alone in inducing remission.

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