Rheumatoid arthritis is a chronic inflammatory disease that causes swelling and stiffness in the joints. It can affect other organs as well. The cause involves genetic and environmental factors. Treatment involves disease-modifying drugs like methotrexate to reduce inflammation and prevent further joint damage. Methotrexate is usually the first drug tried but combinations of medications may be needed to control symptoms and prevent long term disability. Monitoring is important to assess treatment effectiveness and adjust therapies as needed.

1. APPROACH TO AND
RECENT ADVANCES IN
MANAGEMENT OF
RHEUMATOID ARTHRITIS
CHAIR PERSON – DR SACHIN. H
STUDENT – DR VINAL J SHAH

2. INTRODUCTION
 Rheumatoid arthritis is a chronic inflammatory
disease of unknown etiology characterised by a
symmetric polyarthritis.
 RA is primarily considered a disease of the joints,
but abnormal systemic immune responses are
evident.
 Cause a variety of extra-articular manifestations
such as vasculitis, nodules, and accelerated
atherosclerosis. These manifestations clearly show
that RA has features of a systemic disease that can
involve many organs.

3. INCIDENCE & PREVELANCE
Incidence – 0.4 per 1000 females and
0.2 per 1000 males
Prevalence –
World – 0.4 – 1%
Asia – 0.2 – 0.3%
India – 0.1- 0.4% ( harrison 20th
edition)

4. INCIDENCE

5. ETIOPATHOGENES
 Complex and multifaceted
 Genetic factors
 Environmental factors
1. life style factors
- smoking
- nutrition
- medication
- infection
- socioeconomic status
2. host factors
- reproductive factor
- birth weight

6. GENETIC FACTORS
HLA-DRB1 single most strongest known
genetic factor for RA

7.  Non MHC genes includes
1. Protein tyrosine phosphatase non receptor 22
(PTPN22) – encodes lymphoid tyrosine phosphatase,
protein which regulates T and B cell function.
Usually associated with anti-CCP positive disease.
2. Peptidyl arginine deiminase type 4 (PADI4) –
encodes enzyme involved in conversion of arginine to
citrulline and plays a role in development of
citrullinated antigens.
3. Polymorphism of apolipoprotein M (APOM)

8. ENVIRONMENTAL FACTORS
 SMOKING – strongest known environmental risk factor
for RA
 Strongly associated with ACPA and RA factor positively
 Risk increses with duration and packs per day
 MEDICATIONS – studies have shown that HMG CoA
reductase inhibitors(statins) reduce the risk of RA by
40% in patients with dyslipidemia.
 INFECTIONS –
 Epstien barr virus
 Human Parvovirus B19
 Porphyromonas gingivalis ( this virus habours enzyme
peptidyl arginine deiminase with induce antiCCP
antibodies.

9. NUTRITION AND RA

10. PRECLINICAL RA
 The period of autoimmunity preceding the initial
articular signs and symptoms of disease has been
termed pre-clinical RA.
 RF and ACPA can be detected in approximately
one-half of patients, often many years before RA
symptom onset.
 pre-clinical RA is often characterized by the
presence of subclinical inflammation that is
reflected by increased serum levels of C-reactive
protein (CRP) and other pro-inflammatory cytokines
and chemokines.

11. CLINICAL FEATURES
 Age 25-55years, plateaus until 75 yrs
 pain and swelling of the small joints of the hands,
wrists, and feet,
 prolonged morning stiffness, often lasting more
than an hour.
 The systemic features include fatigue and, less
commonly, weight loss or low-grade fever.
 Metacarpophalangeal (MCP), proximal
interphalangeal (PIP), and metatarsophalangeal
(MTP) joints, wrist.

12. ARTICULAR AND BONY DEFORMITIES
 Swan neck deformity

13.  Boutonniere deformity

14.  Z line deformity – subluxation of first MCP joint with
hyperextension of first interphalangeal joint

15.  Ulnar deviation – subluxation of MCP joint, with
subluxation or partial dislocation of proximal
phalanx to volar side.

16.  “Zig-zag” deformity - radial deviation at the wrist
and ulnar deviation at the metacarpophalangeal
joints

17.  Piano key styloid - damage of the ulnar collateral
ligament with resultant prominence, or floating, of
the ulnar head and styloid

18.  RA-related synovitis can involve almost any
synovial joint in the body, the condition
characteristically spares the distal interphalangeal
(DIP) joints (impacting <10% of cases)
 also spares the thoracic and lumbosacral spine.

19. EXTRA ARTICULAR MANIFESTATIONS
 Extra-articular manifestations are observed in up to
50% of patients with RA.
 Associated with poor prognosis, including increased
morbidity and mortality.
 The most significant extra-articular features are
related to vascular inflammation and vascular
damage.
 Mortality risk in patients with RA with extra-articular
manifestations is more than twice that of patients
without extra-articular disease.
 CVS causes accounts for 70% of all deaths in this
group

21. RHEUMATOID NODULES
 occur primarily in seropositive patients with active
disease.
 history of cigarette smoking appears to be a risk
factor for the development of subcutaneous
nodules in RA.
 When present and histologically confirmed,
rheumatoid nodules are pathognomonic for RA.
 most commonly on extensor surfaces and pressure
areas.

23. SECONDARY SJÖGREN’S SYNDROME
 The prevalence of secondary Sjögren’s syndrome
(autoimmune exocrinopathy) has been estimated at
17%.
 symptoms of keratoconjunctivitis sicca (dry eyes) or
xerostomia (dry mouth) are present.

24. PULMONARY MANIFESTATIONS
 Clinically apparent pleuritis may be evident in as
many as 20% of RA cases, and is most common
pulmonary manifestation of RA.
 Pleural effusions in RA are exudative,
 mixed cell counts (predominance of monocytes),
 high protein and lactate dehydrogenase (LDH)
levels,
 low glucose concentrations (resulting from a defect
in the transport of glucose across the pleura)
 low pH.
 Low pH and low fluid glucose, (10 to 50 mg/dL) are
highly characteristic of RA related effusions

25. INTERSTITIAL LUNG DISEASE
 Overall prevelence of ILD in RA is 12%.
 3.5% of individual are diagnosed with ILD even
before joint involvement.
 Radiographs typically demonstrate bibasilar
reticular or reticulonodular patterns in both lung
fields, with a characteristic honeycombing
appearance.
 Usual interstitial pneumonia (UIP) is the most
common pattern seen on HRCT.
 Pulmonary function test shows restrictive pattern,
decreased diffusion capacity of CO

26. CAPLAN’S SYNDROME
 Pulmonary nodulosis and pneumoconiosis following
silica exposure.

27. CARDIOVASCULAR MANIFESTATIONS
 Most frequent side of involvement is pericardium.
 Clinical manifestation is seen in only <10% patients
whereas autopsy finding is seen in 50% of patients
 Cardiomyopathy
 Necrotizing and granulomatous myocarditis
 Coronary artery diseases
 Most common valvular abnormality is mitral
regurgitation.

28. VASCULITIS
 Small to medium vessel vasculitis
 More common in men
 Seen in long standing and RA factor and anti-CCP
postive patients and hypocomplementemia.
 Incidence <1%
 Petechiae, purpura, digital infarcts gangrene, livedo
reticularis,
 Peripheral neuropathy with either a mononeuritis
multiplex or a sensory-related stocking-glove
polyneuropathy.

29. NAIL FOLD INFARCTS
DIGITAL GANGRENE

30. HEMATOLOGICAL MANIFESTATIONS
 Normocytic normochromic anemia is most common
hematological manifestation.
 Increased levels of acute phase reactants like CRP,
ESR, elevated platelet count
 Most common lymphoma is DLBCL
 Felty syndrome seen in <1% patients
1. neutropenia
2. splenomegaly
3. nodular RA

31. 1987 AMERICAN
COLLEGE OF
RHEUMATOLOGY
CRITERIA FOR
CLASSIFICATION
OF RHEUMATOID
ARTHRITIS

32. 2010 AMERICAN
COLLEGE OF
RHEUMATOLOGY
EUROPEAN
LEAGUE AGAINST
RHEUMATISM
CLASSIFICATION
CRITERIA FOR
RHEUMATOID
ARTHRITIS

33. DIFFERENTIATING EARLY RA AND
OSTEROARTHRITIS

34. INVESTIGATIONS
 ESR
 CRP
 RA FACTOR (there are IgM, IgG, IgA isotypes of
RF, most frequentlt measured is IgM , found in 75-
80% of patients)
 ANTI-CCP antibodies (specificity 95%)
 SYNOVIAL FLUID ANALYSIS – RA being
inflammatory arthritis wbc 5000-50,000cells/uL
 JOINT IMAGING –
1. X-RAY
2. USG OF JOINT
3. MRI

35. X-RAY OF JOINTS
FINDINGS –
 Periarticular osteopenia – earliest finding
 Soft tissue swelling
 Symmetric joint space loss
 Subchondral erosions
 Joint destruction in forma of subluxations
and collapse

36. X-RAY OF JOINTS

38. USG OF JOINTS
FINDINGS -
 joint space widening (earliest characteristic
ultrasound finding of synovitis)
 Fluid collection,
 synovial hypertrophy,
 cartilage defects,
 Bone erosions,
 tendon sheath widening & tendon tears.

41. TREATMENT – KEY POINTS
 Rheumatoid arthritis (RA) should be diagnosed
early, and disease-modifying anti-rheumatic drug
(DMARD) therapy should be initiated at the time of
diagnosis.
 Treatment for all patients should be based on a
disease activity target—either remission or low
disease activity.
 The type of DMARD therapy the patient receives is
not as important as ensuring that the treatment
meets the disease activity target.
 The initial DMARD and the cornerstone of therapy
for most patients is methotrexate.

42.  Many patients will require combinations of
DMARDs with or without biologic agents to achieve
the disease activity target.
 Nonsteroidal anti-inflammatory drugs may provide
useful symptom control but are rarely indicated
without concomitant use of DMARDs.
 Glucocorticoids are rapidly effective DMARDs but
have adverse effects. Therefore they should be
used only with other DMARDs and ideally only as a
bridge to effective DMARD therapy.

43. FACTORS ASSOCIATED WITH POOR
PROGNOSIS IN RHEUMATOID ARTHRITIS
 Presence of rheumatoid factor and titer
 Presence of antibodies to CCP and titer
 Presence of shared epitope and number of
alleles
 Presence of erosive disease at presentation
 Presence of nodules or extraarticular
feature
 Smoking currently and in the past
 Obesity

44. INSTRUMENTS USED TO MEASURE RHEUMATOID
ARTHRITIS DISEASE ACTIVITY

45. DSA 28
 Count the number of swollen joint(out of
28joints)
 Count the number of tender joint(out of
28joints)
 Take blood measure of ESR or CRP
 Ask the patient to make global assesment
of health from 0-10
 Final score is calculated by complex
formula.

46. ALGORITHM FOR EARLY DISEASE

47. ALGORITHM FOR ESTABLISHED DISEASE

48. EULAR RECOMENDATION

51. EULAR RECOMMENDATIONS
 Monitoring should be frequent in active disease (every
1–3 months); if there is no improvement by at most 3
months after the start of treatment or the target has
not been reached by 6 months, therapy should be
adjusted
 MTX should be part of the first treatment strategy
 In patients with a contraindication to MTX (or early
intolerance), leflunomide or sulfasalazine should be
considered as part of the (first) treatment strategy
 Short-term glucocorticoids should be considered
when initiating or changing csDMARDs, in different
dose regimens and routes of administration, but
should be tapered as rapidly as clinically feasible

52.  If the treatment target is not achieved with the first
csDMARD strategy, in the absence of poor
prognostic factors, other csDMARDs should be
considered
 If the treatment target is not achieved with the first
csDMARD strategy, when poor prognostic factors
are present, addition of a bDMARD or a tsDMARD
should be considered; current practice would be to
start a bDMARD
 bDMARDs and tsDMARDs should be combined
with a csDMARD; in patients who cannot use
csDMARDs as comedication, IL-6 pathway
inhibitors and tsDMARDs may have some
advantages compared with other bDMARDs

53.  If a bDMARD or tsDMARD has failed, treatment
with another bDMARD or a tsDMARD should be
considered; if one TNF-inhibitor therapy has failed,
patients may receive another TNF-inhibitor or an
agent with another mode of action
 If a patient is in persistent remission after having
tapered glucocorticoids, one can consider tapering
bDMARDs, especially if this treatment is combined
with a csDMARD
 If a patient is in persistent remission, tapering the
csDMARD could be considered

54. CLASS OF DRUGS USED IN RA
NSAIDs
GLUCOCORTICOIDS
Conventional DMARDS
Biological DMARDS

55. NSAIDS
 Adjunctive therapy
 Analgesic and anti inflammatory effects
 Anti inflammatory effects is from non selective
inhibitors of COX1 and COX2
 Side effects –
1. gastritis
2. peptic ulcer disease
3. renal impairment

56. CONVENTIONAL DMARDS
 Methotrexate
 Sulfasalazine
 Hydroxychloroquine
 Leflunomide

57. METHOTREXATE
 Anti-inflammatory and antiproliferative
(immunosuppressive) mechanisms:
 (1) inhibition of aminoimidazole carboxamide
ribonucleotide (AICAR) transformylase (ATIC)
results in increased intracellular and extra-cellular
adenosine POTENT anti inflammatory,
 (2) inhibition of thymidylate synthetase (TYMS)
results in decreased pyrimidine synthesis
 (3) inhibition of dihydrofolate reductase (DHFR)
results in inhibition of transmethylation reactions
essential for cellular functioning.

58. MOA

59.  DOSE – 10-25mg/week orally or
subcutaneously
 Studies have shown the effects of MTX may
be enhanced by splitting the dose (within a
12-hour window) when levels greater than
15 mg/ wk are used, or by using a
subcutaneous route of administration.
 Folic acid 1mg/day to reduce toxicity.
 MTX is available as 2.5, 5, 7.5, 10, and 15
mg tablets, and as a solution of 25 mg/mL
for SQ or IM injection.

60. PRE EVALUATION
Baseline evaluation should include a
 complete blood count (CBC) with platelets,
 hepatitis B and C serology
 liver transaminases
 creatinine.
 Toxicities that require monitoring include
myelosuppression, hepatotoxicity, and pulmonary
toxicity

61. CONTRAINDICATION
 severe renal impairment ( MTX renal
clearence),
 Pulmonary dysfunction
 hepatic impairment,
 pre-existing bone marrow suppression
 alcoholic liver disease
 pregnancy
 breastfeeding

62. ADVERSE EFFECTS AND TOXICITY
 GI symptoms - dyspepsia, nausea, and anorexia,
are common 20% to 70% of patients.
 Hematological - Bone marrow toxicity, is dose
dependent and responds to folic acid
administration. Pancytopenia, leukopenia, anemia,
and thrombocytopenia can occur. 1% to 2% of RA
patients on MTX therapy
 Severe, life-threatening bone marrow toxicity can
be treated with folinic acid (leucovorin) and, if
necessary, granulocyte stimulating factor (GSF).
 Pulmonary - acute interstitial pneumonitis
(hypersensitivity pneumonitis), interstitial fibrosis,
noncardiogenic pulmonary edema

63.  Mucocutaneous - The mucocutaneous toxicities of
MTX, up to one-third of patients, are dose
dependent and respond to folate replacement.
 minor oral ulcerations, but severe ulceration of the
mouth, esophagus, bowel, and vagina can occur,
especially at higher doses.
 Methotrexate Flu - Patients taking MTX may
describe flulike symptoms shortly after taking their
weekly dose. Nausea, low-grade fevers, myalgias
and chills. These side effects usually respond to
supplementation with folic acid, decreasing the
dose, switching from oral to parenteral
administration, or changing the time of the dose to
night.

64.  Nodulosis - The development of, or increase in,
the number or size of rheumatoid nodules has been
reported to occur in patients with RA treated with
MTX, with a prevalence of as much as 8%.

65. MANAGEMENT OF METHOTREXATE TOXICITY
 Folinic acid
 Glucarpidase IV
 For myelosuppression- granulocyte stimulating
factors – filgastrim.

66. LEFLUNOMIDE
MOA –
 Inhibition of DHODH→↓ Pyrimidine synthesis
 Inhibition of tyrosine kinase→↓ Cell signal
transduction
 Ability to block the activation of nuclear factor-κB
(NF-κB) which regulates the expression of genes
important in inflammatory processes
 inhibit neutrophil chemotaxis, which may decrease
the recruitment of inflammatory cells into the joints
DOSE – 10-20mg/dl

67.  DOSE - Standard recommendation is to start
therapy with a loading dose of 100 mg daily for 3
days, then switch to the standard maintenance
dose of 10-20 mg daily

68. PRE EVALUATION
 baseline CBC
 liver enzyme monitoring, including AST, ALT, and
albumin. (enterohepatic recirculation)
 Serum creatinine measurement is important
because leflunomide is partially eliminated by the
kidney.
 Viral hepatitis panel

69. CONTRAINDICATION
 Impaired liver function (The liver is involved in
enterohepatic recirculation and biliary excretion)
 severe renal impairment,
 bone marrow dysplasia,
 severe immunodeficiency,
 severe hypoproteinemia,
 Hypersensitivity to the drug
 Pregnancy
 lacatation

70. ADVERSE EFFECTS AND TOXICITY
 Skin rashes have been reported, most commonly
occurring between the second and fifth months of
treatment and necessitating discontinuation of the
drug.
 Severe skin reactions such as Stevens-Johnson
syndrome or toxic epidermal necrolysis require
leflunomide washout with cholestryramine.
 increased incidence of alopecia.
 can cause interstitial lung disease (ILD), usually
within 3 months of starting therapy.

71. SULFASALAZINE
 Sulfasalazine (SSZ) has anti-microbial and anti-
inflammatory properties, but the exact mechanism
of action is unknown.
 SSZ is commonly used as part of combination
therapy for RA.
 Gastrointestinal intolerance is a common side
effect.
 Although rare, surveillance for leukopenia is
important early in the course of the treatment.

72.  DOSE - 500 mg daily and will escalate the dose by
500 mg/day every week to the standard dose of
1500 to 3000 mg, twice divided daily.
 can inhibit enzymes in the folate-dependent
pathway, concomitant administration of folic acid is
adviced.
ADVERSE EFFECTS –
 Granulocytopenia
 Hemolytic anemia G6PD deficiency

73. HYDROXYCHLOROQUINE
 Hydroxychloroquine (HCQ) is a well-tolerated
DMARD that is commonly used in combination
therapy regimens for RA.
 Doses of HCQ should not exceed 6.5 mg/kg in
chronic therapy to minimize the risk of retinal
toxicity.
 Although routine laboratory monitoring is not
required, ophthalmologic screening is an essential
component of toxicity monitoring.
 Diabetic patients initiating HCQ should be
instructed to follow blood sugars closely because of
the hypoglycemic effects of the drug.
 HCQ is considered safe in pregnancy.

74.  DOSE - HCQ comes in 200 mg tablets
 To prevent ocular toxicity, dosing should be
adjusted for weight.
 HCQ should be maintained at a dose of 6.5 mg/kg
or less for ideal body weight.

75. ADVERSE EFFECT
 HCQ retinopathy is described as bilateral bull’s eye
maculopathy, with retinal pigment epithelial (RPE)
cell depigmentation in the central macula and
sparing of small foveal island. Testing of the
paracentral visual field can usually show toxicity
before RPE changes are visible.
 When advanced, visual loss may be irreversible
and may continue despite cessation of the drug
because of its long half-life in the retina; so early
detection is essential.

76. SAFETY MONITORING

77. SPECIAL SENARIO

78. SUMMARY OF CONVENTIONAL DMARDS

79. BIOLOGICAL DMARDS
 TNF-α inhibitor
1. infliximab
2. adalimumab
3. golimumab
4. certolizumab pegol
5. etanercept
 Anakinra - IL-1 receptor antagonist
 Abatacept – costimulation factor inhibitor
 Rituximab – CD20 inhibitors
 Tocilizumab – IL- 6 receptor inhibitors
 Tofacitinib – JAK1 & JAK3 inhibitors

80. TNF ALPHA INHIBITOR
 Infliximab – chimeric (mouse and human)
 Adalimumab – humanized
 Golimumab – humanized
 Certolizumab pegol – pegylated Fc fragment of
humanised monoclonal antibody
 Etanercept soluble fusion protein comprising of
TNF receptor 2 in covalent linkage with fc portion of
IgG1

81.  MOA -
Decrease Production of Other Inflammatory
Mediators
 Cytokines (e.g., IL-1, IL-6, GM-CSF)
 Chemokines (e.g., IL-8)
 Degradative enzymes (e.g., MMPs)
 Other mediators (e.g., C-reactive protein)
Alter Vascular Function, Leukocyte Traffic and
Activation
 Decreased adhesion molecule expression and function
 Angiogenesis inhibition

82. Modulate the Function of Immunocompetent Cells
 T Cells
 Normalize activation threshold for CD3–T cell
receptor signaling
 Alter Th1/Th2 phenotype, cytokine secretion
 Increase regulatory T cell number and function
 Induce apoptosis (?)
Monocytes and Macrophages
 Modulate HLA-DR expression
 Increase apoptosis (?)

83.  Infliximab – 3mg/kg IV at weeks 0, 2, 6 then every 8
week. May increase dose up to 10mg/kg every 4
weeks.
 Etanercept – 50mg SQ weekly or 25mg biweekly
 Adalimumab – 40mg SQ alternate weeks
 Golimumab – 50mg SQ monthly
 Certolizumab – 400mg SQ week ), 2, 4 then 200mg
alternate weeks.

84. PRE EVALUATION
 LFT
 PPD (look for latent TB)
 Chronic infection HBV, HCV

85. ADVERSE EFFECTS
 Infections (including serious infections)
 Opportunistic infections (e.g., tuberculosis)
 Malignancies (skin cancer, lymphoma [?])
 Demyelinating conditions
 Hematologic abnormalities
 Congestive heart failure
 Autoantibodies (anti-nuclear antibody, anti–double-
stranded DNA)
 Hepatotoxicity
 Dermatologic reactions
 Lupus-like syndromes

86. PREGNANCY AND LACTATION
 TNF inhibitors are classified as U.S. Food and Drug
Administration (FDA) Pregnancy Category B
(animal reproduction studies have failed to
demonstrate a risk to the fetus, and no adequate
and well-controlled studies have been performed in
pregnant women).

87. ANAKINRA
 MOA – IL- 1 receptor antagonist
 DOSE – 100mg SQ daily
 Limited use in RA currently
 Should not be combined with anti TNF drugs due to
high rate of serious infection
 Adverse events –
1. increased risk of bacterial infection
2. reactivation of latent TB
3. neutropenia
 Monitoring –
CBC every month for 3 months
Every 4 months for 1 year

88. ABATACEPT
 MOA – inhibitor of co-stimulation of T cell by blocking
CD28-CD80/86 interaction
 Inhibits the function of antigen presenting cells by
reverse signaling through CD80 and CD86.
 DOSE – weight based
<60kg- 500mg
60-100kg – 750mg
>100kg – 1000mg
IV dose at weeks 0, 2, 4 and then every 4th week OR
125mg SQ weekly

89. RITUXIMAB
 Chimeric monoclonal antibody
MOA –
 directed against CD20, a cell surface molecule
expressed by most mature B cell.
 Reduction in autoantibodies
 Inhibition of T cell activation
 Alteration of cytokines production
 treatment of TNF inhibitor–refractory patients with
RA who have active disease.

90.  Decreases in rheumatoid factor (RF) or anti-
citrullinated rotein antibody (ACPA) serum levels
are reported to be associated with B cell depletion
 Rituximab appears to have greatest benefit in
seropositive patients.
 DOSE – 1000mg IV day x 2, 0 and 14. repeat
course every 24 week
 Premedication – methylprednisolone 100mg to
reduce infusion reaction.

91.  Rituximab has an acceptable safety record in RA
trials, but infusion reactions of variable severity can
occur; most are mild to moderate. The frequency
and severity of infusion reactions are reduced by
the administration of intravenous
methylprednisolone before rituximab infusions.
 A very rare complication in patients with RA who
are treated with rituximab is progressive multifocal
leukoencephalopathy.

92. TOCILIZUMAB
 Humanised monoclonal antibody
 MOA – against membrane and soluble forms of the
IL-6 receptor.
 IL-6 is proinflammatory cytokine implicated in the
RA leading to joint inflammation and damage
 IL-6 activates intracellular signalling leading to
acute phase response, cytokine production and
osteoclast activation.

93.  DOSE – 4-8mg/kg IV monthly
OR
162mg SQ every alternate week (<100kg)
162mg SQ weekly (>100kg)
 ADVERSE EFFECTS –
1. Infusion reaction
2. LFT elevation
3. Dyslipidemia
4. Neutropenia and thrombocytopenia

94. TOFACITINIB
 MOA – JAK1 & JAK3 inhibitor leading to decrease
in cytokines IL-2,4,7,9,15,21, IFN‫ﻵ‬ and IL-6. these
cytokine play roles in promoting T and B cell
activation and inflammation.
 DOSE – 5mg orally BD or 11mg orally daily

95.  ADVERSE EFFECTS -
 Dose-dependent decreases in neutrophils
 Rare significant decreases in hemoglobin, which
could be expected with JAK2 inhibition,
 Lymphopenia (<500/ uL) was seen in less than 1%
of patient.
 MONITORING -
 Complete blood cell (CBC) and total lymphocyte
counts on a regular basis (monthly for 3 months,
then every 3 months)

96. PHYSICAL THERAPY INTERVENTIONS
ACUTE INFLAMMATION -
 Rest and continue physical activity as tolerated
 Passive and active range-of-motion (ROM)
 Isometric exercises
SUBACUTE INFLAMMATION -
 Moderate physical activity (4-5x/week for 30
minutes)
 Dynamic exercises with resistance, aerobic
exercise.

97. INACTIVE/CHRONIC -
 Vigorous physical activity (3x/week for 20 minutes)
or moderate physical activity (5x/week for 30
minutes)
 Dynamic exercises with resistance, aerobic
exercise
 Active ROM

98. NUTRITION AND RA

99. SPECIAL SITUATIONS

100. PREGNANCY AND RA
KEY POINTS –
 RA tends to improve during pregnancy.
 Active RA during pregnancy can result in
lower birth weight infants.
 Preconception planning for inflammatory
arthritis patients may require medication
adjustments: anti-malarials and sulfasalazine
can potentially be continued, methotrexate
and leflunomide must be discontinued.
 TNF inhibitors may be continued if necessary
in second trimester.

101.  75% of female RA patients will show improvement
in symptoms during pregnancy and these
symptoms will flare after delivery.
 Flares during pregnancy is managed by –
1. low dose prednisolone
2. hydroxychloroquine
3. sulfasalazine
MTX and leflunomide for contraindicated in
pregnancy.
 Fetal and Neonatal Outcomes
1 . RA does not increase the rate of fetal loss
during pregnancy.
2. women with active RA during pregnancy are
found to be at risk for giving birth to small for
gestational age infants

102. HIV AND RA
 HCQ
 Sulfasalazine
 Corticosteriod ( high risk of osteonecrosis)
 MTX can be used with certain risk.
 Data regarding biological used is still not available.

103. CONGESTIVE HEART FAILURE
 Combination of DMARDS and non-TNF biological
or tofacitinib.
 TNFi should only be used if there are no other
reasonable options, and then, perhaps, only in
compensated heart failure

104. HEPATITIS B
ACTIVE HEP B INFECTION RECEIVING
/RECEIVED EFFECTIVE ANTIVIRAL TREATMENT
–
 RA treatment should be the same as that of
unexposed patients, as long as the patient’s viral
load is monitored regularly, conservatively, every 6–
12 months.
CHRONIC HEPATITIS B WHO ARE UNTREATED-
 referral for antiviral therapy is appropriate prior to
immunosuppressive therapy

105. HEPATITIS C
ACTIVE HEP C INFECTION RECEIVING
/RECEIVED EFFECTIVE ANTIVIRAL TREATMENT
–
 RA treatment should be the same as that of
unexposed patients
 NOT RECEIVING HCV TREATMENT – consider
using DMARDs other than MTX or leflunomide,
such as sulfasalazine or hydroxychloroquine.

106. VACCINES

107. CASE
 48year old married woman working as a typist in
health office started noticing pain in the hand and
finger in morning after getting up from sleep. Initially
the pain and stiffiness was improving as she used to
work.
 Later the develop pain in the ankle and foot
 So she visited her family physician and was
evaluated
 CBC – normal
 ESR – elevated
 CRP – elevated
 RA factor - negative

108.  Hence she was prescribed NSAIDs initially
 Though symptoms improved but patient still
continued to have pain
 2month Later she noticed some swelling over the
outer surface of forearm.
 she visited the doctor again
 On examination the swelling was nodular, firm
subcutaneous, mobile and painless over extensor
surface of forearm
 Joint examination showed swollen and tender joints
mainly PIP, MCP, wrist

109.  Now patient was re evaluated
 Anti –CCP antibodies titer were significantly high(
more than 3 times the upper lab limit)
 According to ACR-EULAR classification criteria
here score was 7/10
 Patient was planned to be inititated on MTX therapy
 Pre evaluation - complete blood count (CBC) with
platelets, hepatitis B and C serology, liver
transaminases, creatinine was done. And found to
be normal

110.  Patient was initited on MTX 15mg orally every week
and folic acid 1mg rest 6 days of the week
 As the patient had poor prognostic factor i.e
presence of high titre of anti-CCP antibodies and
extra articular manifestation in terms of rheumatoid
nodules
 Patient has to be initiated on triple therapy
 i.e MTX, sulfasalazine and HCQ
 Sulfasalazine 1000mg bd
 HCQ 200mg bd

111.  Patient was monitored monthly for 3month
 During that visit patient was found to have
pancytopenia ( MTX side effect) and
 Pt was started on folinic acid and MTX was
stopped.
 Patient was started on TNF alpha inhibitors and
steriods were started as bridging therapy.
 Adalimumab 40mg SQ alternate week.
 And low dose prednisolone as bridging therpy

112. CASE 2
 55 year old male presented with 8 months history of
painful and swollen joints of the hand, feet, knee
with morning stiffness.
On examination, he was found to have following skin
lesions over his knee, elbow.

113. 1. finger nails showed pitting and oncholysis
2. Dactylitis was present in multiple digits

114. 1. Lab workup showed RA factor negative, CRP was
elevated
X ray showed the following picture

115. CASE 3
 A 45 year old male presented with history of
swelling and deformity of both the feet and hands
for about 10 years.
 Patient had frequent intermittent episodes of
arthritis without morning stiffness. Patient was
treated with NSAIDS with symptomatic
improvement.

116.  Patient developed recurrent painless nodules over
hands and feet as shown below

117.  On examination multiple deformities of PIP, MCP
and MTP as shown below

118.  Skin examination showed subcutaneous nodules of
different size around 1-2cm non tender, fixed to
underlying tissue
 Lab workup revealed
 ESR of 14mm of 1st hour,
 RA factor negative
 uric acid of 14mg/dl,
 CRP 15mg/l

119.  X ray as shown below

120. REFERENCES
 Kellys Rheumatology Edition 2017
 Harrisons Principle Of Internal Medicine 20th
Edition.
 EULAR recommendations for the management of
rheumatoid arthritis with synthetic and biological
disease-modifying antirheumatic drugs: 2016
update
 2015 American College of Rheumatology Guideline
for the Treatment of Rheumatoid Arthritis

121. THANK YOU