Christina Applegate and multiple sclerosis: does the health plan cover the tests that monitor the treatment?

By Ramon Martins Andrade, attorney (OAB/RJ 188.374)

English translation of an article first published in Portuguese: read the original.

In March 2026, the British newspaper The Guardian published an extract from the memoir of the actress Christina Applegate, You With the Sad Eyes. She writes that she was diagnosed with multiple sclerosis in 2021 and that she learned of the disease on a video call in which the neurologist showed her images of her brain: “Here are the lesions”, he said, “There are about 30”. She also describes how she lives with the treatment: “I have infusions every six months to slow the disease’s progress, but those infusions kill all my B cells”, which leaves her, in her own words, prone to infections. She did not name the medicine, and the article does not try to guess it. Nothing is known, or claimed here, about the services, the tests or the clinical choices of her treatment beyond what she herself wrote.

In a few lines, the account brings together the two things that modern treatment of multiple sclerosis needs to keep watch over: the disease, which is seen on MRI, and the medicine itself, which acts on the immune system and demands tests in order to be safe. For those treated through a health plan, the practical question is whether these surveillance tests have the same coverage as the treatment they accompany. The article examines what science knows about this monitoring, what the protocol and the product labels say, how the ANS list of mandatory coverage (the “rol”) treats each test, how three countries have settled the question and what can be demanded.

Two kinds of monitoring: of the disease and of the medicine

The first kind of monitoring measures whether the treatment is working. Relapses, progression of disability and new lesions on magnetic resonance imaging are what the neurologist compares from one assessment to the next. The 2021 international consensus on the use of MRI in multiple sclerosis, which brought together three expert groups from Europe and North America (Wattjes and colleagues, The Lancet Neurology), revised the earlier recommendations to “improve the use of MRI for diagnosis, prognosis, and monitoring” and singled out the three-dimensional FLAIR sequence as the core sequence of the brain scan, precisely for its ability to identify new lesions “to monitor treatment effectiveness”. Follow-up MRI, in other words, is not a luxury test: it is the yardstick by which it is decided whether to keep or switch the medicine, a subject the firm addressed in the article on the medical report when switching the line of treatment (in Portuguese).

The second kind of monitoring measures the price of the treatment. High-efficacy therapies act on the immune system, and each class carries its own risk. Anti-CD20 antibodies, which eliminate B lymphocytes, like those Christina Applegate describes without naming, can reduce the immunoglobulins in the blood. The review by Alvarez and colleagues (Multiple Sclerosis and Related Disorders, 2023) records that, in these patients, hypogammaglobulinaemia “has been associated with an increased risk of infections”, and acknowledges a gap: “there is currently no generally accepted monitoring and treatment approach among clinicians treating patients with MS”. A real-world study of 160 patients on anti-CD20 therapy followed at a tertiary centre (Fernandes and colleagues, Frontiers in Neurology, 2025) found a positive correlation between serious infectious complications and lower IgG levels. It is a retrospective, single-centre study, and it does not set a schedule.

For natalizumab, the dominant risk is a different one: progressive multifocal leukoencephalopathy, PML, an opportunistic infection of the brain caused by the JC virus. The Brazilian protocol describes it as an infection that “may be fatal or result in severe disability” and lists as risk factors the presence of anti-JCV antibodies, more than two years of treatment with natalizumab or fingolimod and prior use of an immunosuppressant. The virus is common. Among 1,102 Brazilian patients with multiple sclerosis tested with the STRATIFY-JCV programme assay, Branco and colleagues (Arquivos de Neuro-Psiquiatria, 2018) found 57.1% with antibodies and a seroconversion rate of 18.5% over 22 months, a profile similar to that described in other countries. Seroconversion explains why the test is repeated: a negative result today does not guarantee tomorrow’s.

In both kinds of surveillance, the test is not an accessory: in immune therapy, it is a condition for the next dose. Which test, at what interval and for which patient is the neurologist’s decision, in the light of the medicine in use and the person’s history.

What the protocol and the product labels say

The Ministry of Health’s Protocolo Clínico e Diretrizes Terapêuticas (PCDT, the clinical protocol and therapeutic guidelines) for multiple sclerosis, approved by Joint Ordinance SAES/SECTICS No. 8/2024, whose annex, according to the Ministry, was amended in June 2025, starts from a premise that is useful outside the SUS (Brazil’s public health system) as well: “In most cases, patient monitoring is clinical and laboratory-based. Monitoring of the adverse events of the medicines or class of medicines must be carried out according to the specific medicine in use.” For the beta interferons, for example, it calls for a full blood count, liver enzymes and bilirubin at 30, 60 and 180 days from the start and every six months thereafter. For natalizumab, it is categorical: “The full blood count must be performed monthly before each infusion”; and, in patients at higher risk of PML, it directs that “at least two MRI scans a year” be established. On the virus, it warns against alarm: “A positive JC virus test does not necessarily determine the development of PML, since the virus is widespread in the population.”

The protocol, however, has no scheme for the anti-CD20 agents used in multiple sclerosis, for a simple reason: its historical table records that Conitec (the national health-technology assessment committee) assessed ocrelizumab and ofatumumab for the indications requested and did not incorporate them into the SUS. For that class, the surveillance rules are in the product labels. The FDA-approved label for ocrelizumab, revised in May 2026, directs hepatitis B screening and immunoglobulin testing before starting; directs, “Prior to every infusion”, a check for active infection; and directs monitoring of immunoglobulins “during OCREVUS treatment and after discontinuation of treatment, until B-cell repletion”. For natalizumab, the product information approved by the European Medicines Agency recommends testing for anti-JCV antibodies before starting, retesting those who are negative “every 6 months”, and having a recent reference MRI, “usually within 3 months”, repeated “at least on a yearly basis”, with more frequent scans, every three or every six months, for those at higher risk.

The picture is uneven: for the medicines in the protocol, the schedule is in a Ministry regulation; for the others, it is in the product labels and in a literature that has yet to reach consensus on immunoglobulins. In every case, the one who translates the general rule to the specific person is the physician who follows them.

In the health plan: what the law guarantees and the rol, test by test

Lei 9.656/1998 (the Health Plans Act) guarantees, in plans with outpatient coverage, “coverage of diagnostic support services, treatments and other outpatient procedures requested by the treating physician” (art. 12, I, “b”). The rule says nothing about protocols, schedules or number of times. RN 465/2021, which is the regulation governing the rol, follows the same logic: the procedures listed in it “shall be subject to mandatory coverage once requested by: I – the treating physician” (art. 6, § 1). Where no protocol sets the schedule, the law has handed the request to the physician in the case.

Annex I of the rol, consolidated up to RN 678/2026, contains almost all of the surveillance tests:

• Full blood count, transaminases (AST and ALT) and TSH: on the rol, with no utilisation guideline.
• Total IgG, IgA and IgM: on the rol, with no guideline.
• Immunophenotyping of lymphocyte subpopulations by flow cytometry, which counts B lymphocytes: on the rol, as a high-complexity procedure, with no guideline.
• Magnetic resonance imaging of the skull (brain): on the rol, high complexity, with no guideline.
• Screening for tuberculosis and hepatitis B before starting: tuberculin skin test and hepatitis B markers on the rol, with no guideline; the interferon-gamma release assay on the rol, but with a utilisation guideline that the request must meet.
• Antibodies to the JC virus: Annex I has no entry under the name of the virus.

Service deadlines come from RN 566/2022 (art. 3): up to 3 working days for clinical laboratory tests, up to 10 working days for other outpatient diagnostic services and up to 21 working days for high-complexity procedures, such as MRI and immunophenotyping. RN 623/2024, in force since July 2025, sets deadlines for responding to a coverage request (art. 12) and requires the operator to put the denial in writing and deliver it to the requester (art. 14). For those who receive infusions at fixed intervals, the deadlines matter: a high-complexity test that takes the maximum time can push back the next dose.

Two boundaries need to be stated. The first is segmentation. In a hospital-only contract, the law guarantees the “complementary tests indispensable for monitoring the course of the disease” during admission (art. 12, II, “d”); surveillance carried out between one infusion and the next, at a laboratory or an imaging clinic, falls outside that segment. The second is frequency. For a test on the rol with no guideline, a refusal on the ground that the patient has “already had it this year” has no support in the text: neither the law nor the entry sets an interval, and a medical request that states the purpose (surveillance of immune therapy, date of the last dose, date of the next) is what dispels the suspicion of unnecessary repetition. A request with no stated purpose, just “full blood count” or just “MRI”, weakens itself.

Anti-JCV is the hard case. Outside the rol on a textual search, coverage passes to art. 10, § 13, of Lei 9.656, inserted by Lei 14.454/2022, which allows a treatment or procedure outside the rol prescribed by the treating physician, with evidence-based proof of efficacy and a therapeutic plan, or with a recommendation from Conitec or from an international health-technology assessment body. The STF (Supreme Federal Court), in ADI 7.265 (decided on 18 September 2025), made that coverage subject to five cumulative criteria, among them prescription by the treating physician, the absence of an adequate alternative on the rol, scientific proof of efficacy and safety and registration with Anvisa (the Brazilian health regulator). Applied to a risk-stratification test, these criteria call for a report that explains why the result changes the course of action, for example in the decision to keep or switch natalizumab, and that shows that no test on the rol performs the same function. The honest answer here is that it depends on the report and on the case.

Those treated through the SUS encounter a different logic: the schedule is the protocol’s, and follow-up follows the organisation of the network, described in the article on Guta Stresser and care between appointments in multiple sclerosis (in Portuguese). One detail of the protocol holds in both worlds. In dealing with tuberculosis screening during follow-up, it provides that “the dispensing of medicines for the underlying disease must not be made conditional on presentation of these tests”. The test keeps watch over the medicine; it is not a pretext for suspending it.

Comparative law: where the monitoring rule lives

The three examples below, read in the official sources, place the same rule in different places: in the product label, in the package of a specialised regime and in a list of diseases.

1. United States: surveillance written into the label

In the United States, the FDA-approved label is the document that defines the conditions of use of the medicine, and the ocrelizumab label sets out the surveillance script: hepatitis B screening and immunoglobulin testing before starting (section 2.1), a check for active infection before each infusion (section 2.2) and monitoring of immunoglobulins during and after treatment, “especially in the setting of recurrent serious infections” (section 5.4). The label is not a coverage law and does not require any insurer to pay for the test; what it does is take surveillance out of the realm of individual preference. When the label itself directs that something be measured before each infusion, the test is part of how the medicine is used.

2. Germany: the test inside the package of the specialised regime

In Germany, the resolution of the Federal Joint Committee (G-BA) of 15 December 2022, which included multiple sclerosis in the specialised outpatient care of § 116b of Book V of the Social Code, defines what the regime covers. The diagnostic list includes “Bildgebende Verfahren (zum Beispiel Ultraschalluntersuchungen, Röntgen, CT, MRT)” and “Laboruntersuchungen”; the treatment list includes “Behandlung von Therapienebenwirkungen” (treatment of adverse effects of therapy) and the planning, delivery and monitoring of treatment. The appendix of billable procedures includes, among others, MRI of the neurocranium and molecular detection of polyomavirus in immunodeficient patients, the family to which the JC virus belongs. The German team design has already been described in the article on care coordination (in Portuguese); what matters here is that surveillance of the therapy is written into the package of the regime itself, and not test by test.

3. France: the disease named, not the test

In France, the Social Security Code provides that the insured person’s share of the costs “peut être limitée ou supprimée” when they suffer from one of the conditions “comportant un traitement prolongé et une thérapeutique particulièrement coûteuse” included in a list set by decree (art. L160-14, 3°). The list in art. D160-4, in force since 1 January 2016, names “sclérose en plaques”. The French path is the reverse of the Brazilian one: instead of examining procedure by procedure, the legislature decided in advance that this disease, because of the prolonged and costly treatment it requires, justifies limiting or removing the patient’s share.

The three models place the monitoring rule in a stable location: the label, the package of the specialised regime, the list of diseases. Brazil has a detailed protocol for the SUS and a rol that covers almost all the tests, but, in the private health-plan sector, it continues to decide surveillance request by request, and it is in that gap that refusals arise.

Liability: what can be demanded, and from whom

The first layer is the operator’s. Since Lei 14.454/2022, Lei 9.656 itself makes health plans subject, at the same time, to the Código de Defesa do Consumidor (CDC, the Consumer Protection Code), and art. 14 of the CDC makes the supplier liable for defects in the service regardless of fault. When the operator authorises the infusion and refuses, or delays beyond the deadlines of RN 566, the test that the label or the protocol requires before it, what you have, in practice, is the suspension of the therapy by another name. The path begins with the written denial, which RN 623 requires the operator to deliver, continues with a complaint to the ANS (the health-plan regulator) and, if necessary, an urgent application to the court, whose strength depends on the medical report. The caveat is that a test outside the rol, such as anti-JCV, does not enjoy the same presumption: there, what was said about § 13 and ADI 7.265 applies.

The second layer is the clinical record. The Code of Medical Ethics (Resolution 2.217/2018 of the CFM, the Federal Council of Medicine) forbids the physician from failing to use the scientifically recognised means at their disposal (art. 32), failing to inform the patient of the diagnosis, prognosis, risks and aims of the treatment (art. 34), failing to keep a medical record with dated entries (art. 87) and denying the patient access to it (art. 88). The Estatuto dos Direitos do Paciente (Lei 15.378/2026, the Patients’ Rights Statute) guarantees care “in a timely manner” (art. 8), participation in the therapeutic plan (art. 11), sufficient information to decide (art. 12, § 1), a second opinion (art. 18) and access to the medical record (art. 19). In immune therapy, these rules have a concrete effect: a test request that states the purpose, the date of the last infusion and the reason for the frequency is at once a clinical act and evidence.

The third layer is harm. When a refusal or an avoidable delay deprives the person of a serious and real possibility of a better outcome, for example by delaying the detection of a complication that the test would have shown, the STJ (Superior Court of Justice) allows compensation for the loss of a chance. The reference precedent is REsp 1.254.141/PR (Third Panel, Justice Nancy Andrighi reporting, decided on 4 December 2012), a case of inadequate treatment of breast cancer, not of multiple sclerosis, whose headnote sets the limit: “The chance, however, can never reach the value of the lost asset”. In multiple sclerosis, proof of the lost chance is a matter for expert evidence, and it begins with the schedule of tests that should have been followed.

Finally, there is a limit that applies to the patient themselves. No denied test authorises postponing, skipping or bringing forward an infusion on one’s own initiative; that decision belongs to the neurologist, who knows the medicine and the history. And fever or signs of infection close to an infusion call for immediate medical assessment, with the therapy in use disclosed, before any discussion about coverage.

Before deciding

In my view, when the test is a condition for the next dose of an infusion that the plan itself has authorised, denying it amounts to suspending the therapy, and coverage of the medicine loses its meaning; for tests on the rol with no guideline, a refusal on grounds of frequency does not hold up. For anti-JCV, the answer depends on the report. In practice, it helps to ask the neurologist, at each start or switch of medicine, for a written surveillance plan: what is measured beforehand, what is repeated and when, what is checked before each infusion. Each request then carries a purpose and a date, and the series of reports becomes the record of the treatment. If a monitoring test has been refused, or if the delay has already pushed the infusion beyond the indicated interval, get in touch with the firm: the analysis starts from the medical request, the written denial and the date of the next dose, and does not replace medical assessment.

About the author

Ramon Martins Andrade (OAB/RJ 188.374) is a lawyer who graduated from UFRJ in 2011, with master’s degrees from Université Sorbonne Nouvelle and from the Naval War College (EGN, Brazilian Navy). He is currently a researcher in Human Rights and Health at ENSP/Fiocruz.

This content is for information and education only. It does not constitute legal advice, advertising of results or any guarantee of outcome, under Rule 205/2021 of the Brazilian Bar Association (OAB).