Barts-MS rose-tinted-odometer: ★★
Guilty as accused!
I did a very one-sided post this weekend on the pros of oral cladribine as a treatment for MS during the COVID-19 pandemic. One commentator asked ‘what about the cons?’. As with all immunosuppressive therapies, there is a risk of secondary malignancies. In fact, both the EMA and FDA labels mention secondary malignancies as a complication of cladribine therapy. We think the short-term cancer risk, i.e. within the first 2 years, was driven by the very low numbers of cases in the placebo arms of phase 3 trials. The cancer rate in the cladribine-exposed subjects was in keeping with the expected background rates compared to subjects on other DMTs and people from the general population from data in an international population-based cancer registry (GLOBOCAN). So I am not convinced that cladribine is associated with a short term cancer risk. However, the jury is out in relation to the intermediate to longterm risk. However, the safety data from the extension and post-marketing surveillance studies look very promising and based on the biology and mode-of-action of cladribine I think this risk is likely to be low.
Although cladribine works via DNA mechanisms it is not a mutagen; i.e. it does not cause mutations in DNA. When cladribine is incorporated into DNA it inhibits DNA polymerases, the enzymes that extend the DNA chain. The cell then senses this as a problem and this triggers apoptosis the biological process that causes the cell to trigger a suicide programme called ‘programmed cell death’. The reason why cladribine is so selective for lymphocytes is that the enzyme that activates cladribine is only found in high concentrations in lymphocytes and the other cells that don’t express this enzyme are resistant to cladribine’s effects.
Saying this secondary malignancy is a complication with all immunosuppressive therapies regardless of their mode of action. The reason is that we rely on peripheral tumour immune surveillance, i.e. our immune system find early cancers and attacks and destroys them. Suppress the immune system intensely enough and for long enough and certain cancers will develop. For example, fingolimod, and I suspect the whole S1P modulator class, is associated with skin cancer (basal and squamous), lymphoma and potentially other cancers, e..g. Kaposi’s sarcoma. Anti-CD20 therapies may be linked to breast cancer. Natalizumab, CNS lymphoma. Alemtuzumab, cervical cancer and possibly thyroid cancer, although one could argue the thyroid cancer risks with alemtuzumab may be due to ascertain bias from the high rate of thyroid screening due to thyroid secondary autoimmunity. The only DMTs not associated with secondary malignancies are the immunomodulators, i.e. interferon-beta, glatiramer acetate and teriflunomide.
Is there anything you can do about the immunosuppressive cancer risk? Yes, there is. You need to enrol and stick to your country’s cancer screening programmes. In the UK there are three national programmes; cervical, breast and colon. Breast cancer screening starts at the age of 50 and stops at the age of 70. Colon cancer screening starts at the age of 50 or 60, which depends on where you live in the UK. Cervical cancer screening is for women between 25 and 64 years of age. However, there is a push to extend cervical cancer screening beyond 64 now that cervical smear screening is being replaced with vaginal swabs, which are self-administered, and use PCR testing to detect HPV, the virus that causes cervical cancer. HPV testing is so much more pleasant for women and more reliable and reproducible than looking for abnormal cells under a microscope.
In the UK the prostate cancer screening programme is available on request, i.e. you can request a PSA (prostate-specific antigen) test. National PSA prostate cancer screening was dropped as the PSA assay was too unreliable. It generated too many false positives or detected very small cancers that were unlikely to cause any problems. In comparison, some of the treatments for prostate cancer cause more harm. In fact, most men who die in old age have asymptomatic prostate cancer at post-mortem; if something else rather than the cancer was going to kill these men why bother about detecting cancer? Please note the dropping of the national prostate cancer screening programme has been controversial and some people think it was a mistake. In many countries, PSA screening is still being done at a national level.
In some parts of the UK, there are pilot lung cancer screening programmes with high-resolution spiral chest CT scans being offered. The early results are very impressive in targeted groups at high-risk of lung cancer such as heavy smokers or ex-smokers. I am convinced that lung cancer screening is likely to become routine in the UK in smokers in the not too distant future.
Other groups for cancer screening include high-risk subjects for example patients with dysplastic naevus syndrome of the skin, who are at risk of melanoma, those with well-defined genetic conditions associated with specific cancers, patients with a very strong family history of specific cancers, patients with inflammatory bowel disease, anal cancer screening in HPV and HIV postive men-who-have-sex-with-men, oesophageal cancer screening in patients with Barrett’s oesophagus, etc.
A few years ago I asked our renal transplant team for advice about their cancer screening programme for their transplant patients. In short, they don’t do anything that is outside of the national cancer screening programme. The reason they gave is that when you start screening a younger population than that defined by the national screening programmes you are likely to detect more false positives cancers, which leads to unnecessary intervention that cause more harm. You also create cancer anxiety syndrome; i.e. patients start to worry excessively about developing cancer. I have a few patients on DMTs who suffer from this condition; so it is real.
However, there are some self-screening programmes that you can engage in, for example, self-examination of your breasts and testes for woman and men, respectively, and the regular examination of worrisome skin lesions. The following are just three YouTube videos on how to do breast, testes and skin lesion self-examinations.
As MS HCPs we are meant to prompt you to make sure you are registered with your GP and are enrolled in the screening programmes. Outside of HPV screening in women about to start an immunosuppressive therapy, I tend to forget to do this. This is another example to have proformas of standardised checklists to make sure we don’t forget this important task.
I would be interested to know what your experience has been with regard to your awareness about cancer risk on immunosuppressive therapies, cancer screening and self-examination. In this study below despite the vast majority of the woman being aware of breast self-examination, a large minority didn’t examine their breasts every month. Does this apply to you?
Watanabe et al. Awareness of Self-Examination, Screening, and Risk Factors for Breast Cancer Among Women Awaiting Care at the Outpatient Clinic of a Mastology Unit. J Cancer Educ. 2020 Oct 9. doi: 10.1007/s13187-020-01892-1.
This study aimed to evaluate the awareness and practice of breast self-examination (BSE) and the awareness of screening and risk factors for breast cancer among patients from a mastology clinic and to associate such findings with sociodemographic factors of that population. A total of 202 randomly selected patients from the outpatient clinic of the Mastology Unit of São Paulo School of Medicine were interviewed. A structured questionnaire was used and included questions regarding sociodemographic variables, questions to assess the knowledge and practice of BSE, and knowledge of mammographic screening and risk factors for breast cancer. The vast majority of patients were aware of the existence of BSE (93.1%). BSE was performed by most patients (64.9%), although only 20.3% performed it adequately. Only 21.8% of respondents showed awareness of the best screening method for breast cancer. Furthermore, 17.3% of patients showed adequate awareness of risk factors for breast cancer. The analysis of sociodemographic variables showed that older, postmenopausal, and less-educated women showed better practice of BSE. Overall, the patients had no adequate awareness of BSE, mammographic screening, and risk factors for breast cancer, and the majority failed to practice BSE adequately, particularly the group of patients with the higher level of education. These data show that educational measures regarding the practice of BSE and, especially, mammograms should be emphasized, regardless of education level or family income of the patient.
PS (4-Mar-2021): In response to a request from one of the comments in the survey: “…you could you please comment on cancer risk for anti CD20+ treatments, as well as cancer-related topics for younger pwMS”. I have therefore added the presentation from Professor Hauser from the MSVirtual2020, the 8th Joint ACTRIMS-ECTRIMS Meeting, from September 2020. As you can see the rate of malignancies and female breast cancer in ocrelizumab-treated patients remained broadly within the range reported in the general population from epidemiological data. Please note these patients have been followed for over 7 years. I hope this helps.
CoI: multiple
Twitter: @gavinGiovannoni Medium: @gavin_24211
#MSCOVID19: immunosuppression & vaccine-readiness
It is always a good idea to learn from others. We have stressed that the uneventful recovery from COVID-19 involves two processes. Firstly, an appropriate antiviral response, which is needed to clear the virus and secondly an anti-inflammatory response to prevent the delayed immunological damage to the lung that triggers ARDS (acute respiratory distress syndrome), which is the main cause of death with COVID-19. There clearly is a balancing act as if you suppress the delay immune response too much you may prevent clearing of the virus and ongoing damage from viral replication.
It is very heartening to see that patients with other immune-mediated inflammatory disorders that are on immunosuppressive therapies, predominantly biological therapies, are not at increased risk of severe COVID-19 (see Haberman et al below). This experience is mirroring our experience in MS.
However, in the transplant field where the levels of immunosuppression are an order of magnitude more intense, the message is mixed. Liver transplant recipients seem to do fine (see D’Antiga below) but in kidney transplant recipients those with the greatest T-cell depletion, particularly those who receive ATG (anti-thymocyte globulin), do the worst and have high mortality from COVID-19 (see Akalin below). The reason for the difference between liver transplant recipients and ATG-treated kidney transplant recipients are T-cells. ATG is one of the most potent T-cell depleting agents we have and rendering someone severely deficient in T-cells puts them at high risk of viral, in particular severe viral, infections. The latter does not only include exogenous (outside the body) viral infections such as SARS-CoV-2 but endogenous (inside the body) latent viruses such as CMV and EBV. The ATG treated transplant patients are likely to be succumbing to uncontrolled SARS-CoV-2 infection rather than the delayed immunological reactions or ARDS.
What this is telling us is that moderate immunosuppression, with reasonable T-cell counts and T-cell function, does not increase your risk of getting COVID-19 or severe COVID-19 and may reduce your risks of the latter. However, as soon as you drop your T-cell counts and profoundly suppress T-cell function you are increased risk of severe COVID-19, probably from uncontrolled viral replication.
So how is this relevant to MS? As always it is a balancing act between being sufficiently immunosuppressed to prevent the immunological complications of SARS-CoV-2, but not too immunosuppressed that you can’t control the viral infection. In my opinion, in the MS space, the only treatments that we need to be concerned about are the acute effects of alemtuzumab and HSCT on the immune system in the depletion phase of treatment, i.e. the initial 3-6 months until total lymphocyte counts recover to a level that gives you adequate anti-viral responses. I have set the latter at above 500/mm3 in younger pwMS and above 800/mm3 on older people (older than 60 years of age). The reason for the latter is that as you get older and develop immunosenescence the proportion of your T-cells that are naive and able to respond to new viruses and antigens shrinks. This may explain why older people are at more risk of getting severe COVID-19, i.e. their immune systems are just not as good at responding to new viral infections.
There is a third phase to SARS-CoV-2 and that is the delayed antibody response, which is B-cell dependent. The antibodies probably contribute to the tissue damage in the immune-mediated phase of COVID-19. However, you clearly don’t need B-cells and antibodies to recover from COVID-19. I base this on the case reports of two patients with agammaglobulinaemia from Italy who recovered from COVID-19. Please remember these patient don’t have B-cells. Another clue that B-cells are not needed is the fact that patients on anti-CD20 therapies tend to deal with viral infections, including novel or new viral infection, well and rarely get severe viral infections. The latter observation is borne out by how well anti-CD20 patients are weathering the COVID-19 storm.
The one downside of anti-B-cell therapies, however, is that you may need anti-SARS-CoV-2 antibodies to prevent yourself from getting reinfected with the virus. The latter has major implications for when a SARS-CoV-2 vaccine arrives. Will pwMS on anti-CD20 therapies be able to respond to a vaccine? Based on the fact that the SARS-CoV-2 spike protein, the main immunogen in future vaccines, is heavily glycosylated and that anti-CD20 therapies block antibody responses to glycoproteins (proteins covered in sugar molecules) patients on anti-CD20 therapies are unlikely to be vaccine ready unless their dosing is interrupted to allow peripheral B-cell recovery.
It is clear from social media activity and exchanges with my colleagues that many of us are now moving onto the next phase of preparedness for managing MS during COVID-19, i.e. how to ensure your patients are vaccine ready for a SARS-CoV-2 vaccine. The latter is something I have discussed before and is why I have added another column to my DMT table (version 4).
Haberman et al. Covid-19 in Immune-Mediated Inflammatory Diseases — Case Series from New York. N Engl J Med 2020 Apr 29. doi: 10.1056/NEJMc2009567.
A better understanding of the implications of Covid-19 in patients with immune-mediated inflammatory disease and the effects of anti-cytokine and other immunosuppressive therapies is urgently needed to guide clinicians in the care of patients with psoriasis, rheumatoid arthritis, psoriatic arthritis, inflammatory bowel disease, and related conditions. Although our analysis was limited in sample size, our data reveal an incidence of hospitalization among patients with immune-mediated inflammatory disease that was consistent with that among patients with Covid-19 in the general population in New York City reported by the New York City Department of Health and Mental Hygiene (35,746 of 134,874 patients [26%]) (Table S5). These findings suggest that the baseline use of biologics is not associated with worse Covid-19 outcomes.
Lorenzo D’Antiga. Coronaviruses and Immunosuppressed Patients: The Facts During the Third Epidemic. Liver Transplantation 20 March 2020.
… the available data on past and present coronavirus outbreaks suggest that immunosuppressed patients are not at increased risk of severe pulmonary disease compared with the general population. Children under the age of 12 years do not develop severe coronavirus pneumonia, regardless of their immune status, although they get infected and can, therefore, spread the infection. The risk factors for severe disease remain old age, obesity and its complications, other comorbidities, and male sex. Although the surveillance of this particular group of patients should continue, there are no reasons to postpone lifesaving treatments, such as transplantation or chemotherapy for cancer, during coronavirus outbreaks both in children and in adults.
Akalin et al. Covid-19 and Kidney Transplantation. N Engl J Med. 2020 Apr 24.
In conclusion, at our institution, kidney-transplant recipients with Covid-19 had less fever as an initial symptom,3 lower CD3, CD4, and CD8 cell counts,4 and more rapid clinical progression than persons with Covid-19 in the general population. The number of our patients with very low CD3, CD4, and CD8 cell counts indirectly supports the need to decrease doses of immunosuppressive agents in patients with Covid-19, especially in those who have recently received antithymocyte globulin, which decreases all T-cell subsets for many weeks. Our results show a very high early mortality among kidney-transplant recipients with Covid-19 — 28% at 3 weeks as compared with the reported 1% to 5% mortality among patients with Covid-19 in the general population who have undergone testing in the United States and the reported 8 to 15% mortality among patients with Covid-19 who are older than 70 years of age.
CoI: multiple
#MSCOVID19 – DMT update (2)
This week saw several bits of information appear that has led me to change my position on several DMTs in terms of their risk for pwMS during the COVID-19 pandemic.
Firstly, the verbal update by Maria Pia-Sormani on the Italian cohort of patients with MS who had COVID-19. These figures were given during the iWiMS weekly COVID-19 &MS webinar. There are now 380 cases of pwMS and COVID-19 reported in the Italian register with only 5 deaths. The mortality rates are well below that of the general population and suggest that pwMS are not at increased risk of severe COVID-19. This is good news. This data also supports the hypothesis that mild-to-moderate immunosuppression may be good and in fact, reduce the chances of pwMS getting severe COVID-19. This is not surprising as severe COVID-19 is almost certainly immune-mediated disorder. The five patients that died (see table below) tended to be older, have more advanced disease and comorbidities.
It is now clear that SARS-CoV-2 is neurotropic with the second, but first published, case of meningoencephalitis with virus detectable in the spinal fluid. This now increases the risk of natalizumab for pwMS. You don’t want to be on natalizumab if SARS-CoV-2 disseminates to the CNS. It is very important that if you are on natalizumab and get COVID-19 that you look-out for CNS symptoms. The fact that most MS centres have shifted their patients onto EID (extended interval dosing) will reduce this risk but it remains concerning. For more information on how EID reduces this risk please see my explanation on MS-Selfie.
At a personal level I have now 6 patients with MS on various DMTs who have all come through having had COVID-19 without any problems. I have asked them to register themselves on the MS register study and I will be reporting them next week.
I would urge you to watch the weekly iWiMS webinar which will keep the MS community up-to-date with what is happening in relation to COVID-19 and MS.
I therefore updated my table and have added a ranking to reflect the changing advice. Please note I have downgraded the risk associated with anti-CD20 therapies based on the emerging evidence as well. More on this later.
Moriguchi et al. A First Case of Meningitis/Encephalitis Associated With SARS-Coronavirus-2. Int J Infect Dis 2020 Apr 3 PMID: 32251791
Novel coronavirus (SARS-Coronavirus-2:SARS-CoV-2) which emerged in Wuhan, China, has spread to multiple countries rapidly. We report the first case of meningitis associated with SARS-CoV-2 who was brought in by ambulance due to a convulsion accompanied by unconsciousness. He had never been to any foreign countries. He felt generalized fatigue and fever (day 1). He saw doctors nearby twice (day2 and 5) and was prescribed Laninamivir and antipyretic agents, His family visited his home and found that he was unconsciousness and lying on the floor in his vomit. He was immediately transported to this hospital by ambulance (day 9). Under emergency transport, he had transient generalized seizures that lasted about a minute. He had obvious neck stiffness. The specific SARS-CoV-2 RNA was not detected in the nasopharyngeal swab but was detected in a CSF. Anti- HSV 1 and varicella-zoster IgM antibodies were not detected in serum samples. A brain MRI showed hyperintensity along the wall of right lateral ventricle and hyperintense signal changes in the right mesial temporal lobe and hippocampus, suggesting the possibility of SARS-CoV-2 meningitis. This case warns the physicians of patients who have CNS symptoms.
CoI: multiple
Does immunosuppression protect you from severe COVID-19?
The hypothesis that immunosuppression may protect you from severe COVID-19 is gaining traction. New data released on the 4th April 2020 from the UK’s Intensive Care National Audit & Research Centre suggests it may. When comparing 2249 patients admitted to ITU in the UK with severe COVID-19 the proportion of immunocompromised patients was 3.7x lower than the proportion of immunocompromised patients admitted to ITU with viral pneumonia (the comparator) between 2017 and 2019 (2.3% vs. 8.5%). This was a highly significant difference (p<0.00001).
This clearly justifies the current research strategy being tested across the planet to see if immunosuppressive therapies may improve disease outcome in patients with COVID-19.
Does this mean we can now assume that immunosuppression protects against severe COVID-19 and COVID-19-related ARDS (adult respiratory distress syndrome)? Not yet. The UK’s ITU cohort of severe COVID-19 is biased in that those patients who are deemed too frail and/or disabled may never get to ITU, which may include a disproportionate number of immunosuppressed patients. Whereas this specific bias is unlikely to apply to ITU admissions between 2017 and 2019 (viral pneumonia cohort) when there was no such pressure on resources.
Despite this caveat, this is an important tidbit of information that will allow pwMS on immunosuppression to sleep a bit easier. I sincerely hope the wider MS community will reconsider their advice about not giving MS DMTs that are if anything mildly immunosuppressive to patients with active MS. By not treating our patients we may unintentionally be increasing their chances of developing severe COVID-19. Could our guidelines be another example of the law of unintended consequences? Let’s hope the real-world data that is being collected at present will answer this question.
CoI: multiple
To vaccinate or not?
Should your vaccine status be checked and updated before you start treatment?
As part of our programme to derisk disease-modifying therapies (DMTs) for pwMS in our service, we are reviewing our vaccination policy. One issue that has emerged is the possible need to boost immunity to certain types of bacteria that are known to pose a risk in patients on long-term immunosuppression, in particular B cell depleters, such as rituximab, ocrelizumab and ofatumumab. Why?
Chronic B-cell depletion essentially prevents B-cells mounting an adequate antibody response to new antigens. It does this by preventing the formation of so-called germinal centres in the spleen and/or lymph nodes. In other words patients on longterm anti-CD20 therapy behave, from an immunological perspective, if they have had a functional splenectomy. This put patients with longterm B cell depletion at risk of hypogammaglobulinaemia (low immunoglobulin levels) in the future and predisposes them to infections caused by so-called encapsulated bacteria; these include pneumococcus, meningococcus and Haemophilus Influenzae.
When you review the rheumatoid arthritis literature in relation to longterm rituximab (anti-CD20) therapy both these problems have been documented. How do the rheumatologists deal with these problems? They appear to routinely monitor immunoglobulin levels and they proactively vaccinate their patients prior to starting long-term anti-CD20 therapy.
It seems pretty obvious to me, reading the rheumatology literature, that before you start long-term anti-CD20 therapy you should have your vaccination status checked and we should start vaccinating patients against pneumococcus, meningococcus and Haemophilus Influenzae B. In fact, pneumococcal vaccine is already recommended, if possible, for all patients before starting immunosuppressive treatments. It is clear for anti-CD20 therapies that the vaccines will need to be given prior to starting treatment (see Nguyen paper below).
We also recommend doing baseline immunoglobulin levels on all patients before starting treatment as a reference and then to start checking levels from year 3 onwards. I say year 3 because in the ocrelizumab trials we only saw a significant drop in IgM and IgA levels over 2 years and IgG levels were stable. Based on the rituximab data a drop in IgG levels is, therefore, only likely to emerge after 2 years of treatment.
I would be interested to know if any of you had your vaccine status discussed before you started maintenance immunosuppression?
Makatsori et al. Hypogammaglobulinaemia after rituximab treatment-incidence and outcomes. QJM. 2014 Oct;107(10):821-8.
BACKGROUND: Rituximab, a chimeric monoclonal antibody against CD20, is increasingly used in the treatment of B-cell lymphomas and autoimmune conditions. Transient peripheral B-cell depletion is expected following rituximab therapy. Although initial clinical trials did not show significant hypogammaglobulinaemia, reports of this are now appearing in the literature.
METHODS: We performed a retrospective review of patients previously treated with rituximab that were referred to Clinical Immunology with symptomatic or severe hypogammaglobulinaemia. Patient clinical histories, immunological markers, length of rituximab treatment and need for intravenous immunoglobulin replacement therapy (IVIG) were evaluated. An audit of patients receiving rituximab for any condition in a 12-month period and frequency of hypogammaglobulinaemia was also carried out.
RESULTS: We identified 19 post-rituximab patients with persistent, symptomatic panhypogammaglobulinaemia. Mean IgG level was 3.42 ± 0.4 g/l (normal range 5.8-16.3 g/l). All patients had reduced or absent B-cells. Haemophilus Influenzae B, tetanus and Pneumococcal serotype-specific antibody levels were all reduced and patients failed to mount an immune response post-vaccination. Nearly all of them ultimately required IVIG. The mean interval from the last rituximab dose and need for IVIG was 36 months (range 7 months-7 years). Of note, 23.7% of 114 patients included in the audit had hypogammaglobulinaemia.
CONCLUSION: With the increasing use of rituximab, it is important for clinicians treating these patients to be aware of hypogammaglobulinaemia and serious infections occurring even years after completion of treatment and should be actively looked for during follow-up. Referral to clinical immunology services and, if indicated, initiation of IVIG should be considered.
Nguyen et al. Initial Serological Response after Prime-boost Pneumococcal Vaccination in Rheumatoid Arthritis Patients: Results of a Randomized Controlled Trial. J Rheumatol. 2017 Dec;44(12):1794-1803.
OBJECTIVE: To evaluate the initial serological responses to pneumococcal vaccination with the 13-valent protein-conjugated pneumococcal vaccine (PCV13) followed by the 23-valent polysaccharide pneumococcal vaccine (PPV23) among patients with rheumatoid arthritis (RA) treated with biological disease-modifying antirheumatic drugs (bDMARD) according to dosing and intervals between immunizations.
METHODS: Investigator-initiated clinical trial. Patients with RA receiving bDMARD were randomized (1:1:1) to immunization with single dose PCV13 followed by PPV23 after 16 or 24 weeks, or double dose PCV13 followed by PPV23 after 16 weeks. A comparison group of patients with RA treated with conventional synthetic (cs)DMARD received single dose PCV13 followed by PPV23 16 weeks later. Pneumococcal antibodies were collected before and 4 weeks after each vaccination. The primary endpoint was the proportion of participants responding to ≥ 6/12 pneumococcal serotypes 4 weeks after both vaccinations.
RESULTS: Sixty-five participants receiving bDMARD and 35 participants receiving csDMARD were included. After PPV23 vaccination, 87% (95% CI 0.76-0.94) and 94% (95% CI 0.77-0.99), respectively, of participants treated with bDMARD and csDMARD had reached the primary endpoint. There was no significant difference in primary endpoint between the 3 randomization arms. The response for rituximab-treated participants was 25% compared to ≥ 89% in participants treated with bDMARD with other mode of action.
CONCLUSION: The early serological response to prime-boost vaccination with PCV13 followed by PPV23 was very similar among participants receiving bDMARD and csDMARD. However, notable differences in response were observed according to individual bDMARD. It is important to consider the RA treatment when planning pneumococcal vaccination in patients with RA.
Friedman & Winthrop. Vaccinations for rheumatoid arthritis. Curr Opin Rheumatol. 2016 May;28(3):330-6.
PURPOSE OF REVIEW: Rheumatoid arthritis (RA) patients experience increased infectious disease-related morbidity and mortality, and vaccinations represent an important element in their care. However, vaccine immunogenicity can be affected by disease-modifying antirheumatic drug (DMARD) therapy, such that vaccine choice and timing can be clinically challenging. We review the indications, safety, and immunogenicity of vaccines in the setting of RA.
RECENT FINDINGS: Recent recommendations highlight the use of influenza, pneumococcal, and shingles vaccines in RA patients. Studies suggest influenza and pneumococcal vaccines are underutilized, but well tolerated in RA patients and generally immunogenic during DMARD use with the exception of rituximab. Though data for other nonlive vaccines are more limited, hepatitis B virus and human papilloma virus vaccines also appear well tolerated and immunogenic in this population. Live vaccines for shingles and yellow fever remain contraindicated in some RA patients; however, limited data suggest they might be well tolerated in certain individuals.
SUMMARY: The review updates rheumatologists on the optimal use and timing of routine vaccinations in the care of RA.
CoI: multiple